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Associations between grasses and soil microorganisms can strongly influence plant community structures. However, the associations between grass productivity and diversity and soil microbes, as well as the patterns of co-occurrence between grass and microbes remain unclear. Here, we surveyed grass productivity and diversity, determined soil physicochemical, and sequenced soil archaea, bacteria and fungi by metabarcoding technology at 16 alpine grasslands. Using the Distance-decay relationship, Inter-Domain Ecological Network (IDEN), and Mantel tests, we investigated the relationship between grass productivity, diversity and microbial diversity, and the patterns of co-occurrence between grass and microbial inter-domain network in alpine grassland. We found the archaea richness, bacteria richness and Shannon, and fungi α-diversity were significantly negatively correlation with grass diversity, but archaea and bacteria diversity were positively correlation with grass productivity. Moreover, an increase in microbial β-diversity was observed along with increased discrepancy in grass diversity and productivity and soil variables. Variance partitioning analysis suggested that the contribution of grass productivity on microbial community was higher than that of soil variables and grass diversity, which implies that microbial community was more related to grass productivity. Inter-Domain Ecological Network showed that the grass species formed complex and stable ecological networks with some bacterial, archaeal, and fungal species, and the grass-fungal ecological networks showed the highest robustness, which indicated that soil fungi could better co-coexist with aboveground grass in alpine grasslands. Besides, the connectivity degrees of the grass-microbial network were significantly positively correlated with grass productivity, suggesting that the coexistence pattern of grasses and microbes had a positive feedback effect on the grass productivity. The results are important for establishing the regulatory mechanisms between plants and microorganisms in alpine grassland ecosystems.

Lake Qinghai has shrunk and then expanded over the past few decades. Quantifying the contributions of climate change and human activities to lake variation is important for water resource management and adaptation to climate change. In this study, we calculated the water volume change of Lake Qinghai, analyzed the climate and land use changes in Lake Qinghai catchment, and distinguished the contributions of climate change and local human activities to water volume change. The results showed that lake water volume decreased by 9.48 km3 from 1975 to 2004 and increased by 15.18 km3 from 2005 to 2020. The climate in Lake Qinghai catchment is becoming warmer and more pluvial, and the changes in land use have been minimal. Based on the Soil and Water Assessment Tool (SWAT), land use change, climate change and interaction effect of them contributed to 7.46%, 93.13% and −0.59%, respectively, on the variation in surface runoff into the lake. From the perspective of the water balance, we calculated the proportion of each component flowing into and out of the lake and found that the contribution of climate change to lake water volume change was 97.55%, while the local human activities contribution was only 2.45%. Thus, climate change had the dominant impact on water volume change in Lake Qinghai.

Gross primary production (GPP) plays a crucial part in the carbon cycle of terrestrial ecosystems. A set of validated monthly GPP data from 1957 to 2010 in 0.5° × 0.5° grids of China was weighted from the Multi-scale Terrestrial Model Intercomparison Project using Bayesian model averaging (BMA). The spatial anomalies of detrended BMA GPP during the growing seasons of typical El Nino years indicated that GPP response to El Nino varies with Pacific Decadal Oscillation (PDO) phases: when the PDO was in the cool phase, it was likely that GPP was greater in northern China (32°–38°N, 111°–122°E) and less in the Yangtze River valley (28°–32°N, 111°–122°E); in contrast, when PDO was in the warm phase, the GPP anomalies were usually reversed in these two regions. The consistent spatiotemporal pattern and high partial correlation revealed that rainfall dominated this phenomenon. The previously published findings on how El Nino during different phases of PDO affecting rainfall in eastern China make the statistical relationship between GPP and El Nino in this study theoretically credible. This paper not only introduces an effective way to use BMA in grids that have mixed plant function types, but also makes it possible to evaluate the carbon cycle in eastern China based on the prediction of El Nino and PDO.

The terrestrial methane budget varies between different vegetation types and soil conditions and is highly uncertain for alpine grasslands. This work used eddy covariance techniques to continuously measure CH4 flux (NEEm) over a semiarid alpine meadow on the northeastern Qinghai-Tibetan Plateau from January 2017 to August 2019. The diel NEEm averaged 0.14 ± 0.98 nmol CH4 m−2 s−1 (mean ± S.D.), with a rough pattern of daytime release and nocturnal uptake. The 8-day NEEm exhibited a similar sinusoid variation, with a peak of 6.8 mg CH4 m−2 d−1 at the end of April and a minimum of −1.5 mg CH4 m−2 d−1 at the end of August. The maximum release probably coincided with the thawing of frozen soil in the root zone, and the peak uptake may be related to high soil temperature. Monthly CH4 uptake was highest from June to September and consumed 51.7 mg CH4 m−2 from the atmosphere. CH4 production in the other months totaled 647.6 mg CH4 m−2. The semiarid alpine meadow thus acted as a weak net CH4 source, releasing ca 0.6 g CH4 m−2 year−1 to the atmosphere. The boosted regression trees analysis shows that the sensible heat flux (H) is positively related to half-hour NEEm and accounted for 34% of its variability. The piecewise structural equation models reveal that the magnitude of the effects from soil temperature and vapor pressure deficit on 8-day and monthly NEEm were almost equal, but acted in opposite directions. Vegetation growth and soil moisture exerted little direct influence on NEEm variability at half-hour, 8-day, or monthly scales. Our results show that CH4 emissions of the nongrowing season dominate the annual methane budget for this alpine meadow area. Methane consumption during the growing season was significantly constrained by low soil temperature and high soil water content. These findings imply that semiarid alpine meadows may consume more methane during the growing season if soil temperatures increase and soil moisture levels decrease as projected by future warming scenarios, thus constituting a climate change negative feedback.

Damaged hyaline cartilage has no capacity for self-healing, making osteoarthritis (OA) “difficult-to-treat”. Cartilage destruction is central to OA patho-etiology and is mediated by matrix degrading enzymes. Here we report decreased expression of miR-17 in osteoarthritic chondrocytes and its deficiency contributes to OA progression. Supplementation of exogenous miR-17 or its endogenous induction by growth differentiation factor 5, effectively prevented OA by simultaneously targeting pathological catabolic factors including matrix metallopeptidase-3/13 (MMP3/13), aggrecanase-2 (ADAMTS5), and nitric oxide synthase-2 (NOS2). Single-cell RNA sequencing of hyaline cartilage revealed two distinct superficial chondrocyte populations (C1/C2). C1 expressed physiological catabolic factors including MMP2, and C2 carries synovial features, together with C3 in the middle zone. MiR-17 is highly expressed in both superficial and middle chondrocytes under physiological conditions, and maintains the physiological catabolic and anabolic balance potentially by restricting HIF-1α signaling. Together, this study identified dual functions of miR-17 in maintaining cartilage homeostasis and prevention of OA.

How vegetation phenology responds to climate change is a key to the understanding of the mechanisms driving historic and future changes in regional terrestrial ecosystem productivity. Based on the 250-m and 8-day moderate resolution imaging spectroradiometer (MODIS) normalized difference vegetation index (NDVI) data for 2000–2014 in the Three-River Source Region (TRSR) of Qinghai Province, China, i.e., the hinterland of the Tibetan Plateau, we extracted relevant vegetation phenological information (e.g., start, end, and length of growing season) and analyzed the changes in the TRSR vegetation in response to climate change. The results reveal that, under the increasingly warm and humid climate, the start of vegetation growing season (SOS) advanced 1.03 day yr−1 while the end of vegetation growing season (EOS) exhibited no significant changes, which led to extended growing season length. It is found that the SOS was greatly affected by the preceding winter precipitation, with progressively enhanced precipitation facilitating an earlier SOS. Moreover, as the variations of SOS and its trend depended strongly on topography, we estimated the elevation break-points for SOS. The lower the elevations were, the earlier the SOS started. In the areas below 3095-m elevation, the SOS delay changed rapidly with increasing elevation; whereas above that, the SOS changes were relatively minor. The SOS trend had three elevation break-points at 2660, 3880, and 5240 m.

The CreER/LoxP system is widely accepted to track neural lineages and study gene functions upon tamoxifen (TAM) administration. We have observed that prenatal TAM treatment caused high rates of delayed delivery and fetal mortality. This substance could produce undesired results, leading to data misinterpretation. Here, we report that administration of TAM during early stages of cortical neurogenesis promoted precocious neural differentiation, while it inhibited neural progenitor cell (NPC) proliferation. The TAM-induced inhibition of NPC proliferation led to deficits in cortical neurogenesis, dendritic morphogenesis, synaptic formation, and cortical patterning in neonatal and postnatal offspring. Mechanistically, by employing single-cell RNA-sequencing (scRNA-seq) analysis combined with in vivo and in vitro assays, we show TAM could exert these drastic effects mainly through dysregulating the Wnt-Dmrta2 signaling pathway. In adult mice, administration of TAM significantly attenuated NPC proliferation in both the subventricular zone and the dentate gyrus. This study revealed the cellular and molecular mechanisms for the adverse effects of TAM on corticogenesis, suggesting that care must be taken when using the TAM-induced CreER/LoxP system for neural lineage tracing and genetic manipulation studies in both embryonic and adult brains.

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., The authors of this study compile data on spatial and temporal dynamics of surface water bodies across China, covering a time span from 1989 – 2016. The study describes hot-spot areas with strongly decreasing trends in surface water area and terrestrial water storage in North China and discusses implications of water resources and security in China.

Neural repair within the central nervous system (CNS) has been extremely challenging due to limited abilities of adult CNS neurons to regenerate, particularly in a highly inflammatory injury environment that is also filled with myelin debris. Spinal cord injury (SCI) is a serious medical condition that often leads to paralysis and currently has no effective treatment. Here we report the construction of a novel biocompatible and biodegradable material, Bio-C, through coating of acid-desalted-collagen (ADC) tube with pre-modified hyaluronic acid, which, after implantation, can elicit quite robust neural regeneration and functional recovery after complete spinal-cord transection with a 2 mm–spinal-cord-segment removal in mice. We combined morphological, electrophysiological, and objective transcriptomic analyses, in addition to behavioral analyses, to demonstrate neural tissue regeneration and functional recovery through the establishment of Bio-C-induced anti-inflammatory, neurogenic, and neurotrophic microenvironment. Through this study, we unveiled the underlying logic for CNS neural repair.

Forest ecosystems play a significant role in climate change mitigation and uptake a larger amount of atmospheric CO2 than other terrestrial ecosystems via photosynthesis process in form of gross primary production (GPP). The photosynthesis or GPP is largely determined by the photosynthetic capacity of vegetation (i.e., maximum rate of carboxylation, Vcmax) in ecosystem models. However, considerable uncertainties of Vcmax estimates may limit our potential to address scientific issues of GPP related to the increasing emission of atmospheric CO2. Recently, solar-induced chlorophyll fluorescence (SIF) signals have been used as a proxy for resolving photosynthesis. In this study, the biochemical and structural parameters were retrieved from hyperspectral reflectance and fluorescence quantum efficiency (FQEs) was retrieved from ground-based SIF. Then, retrieved parameters were incorporated into the Soil Canopy Observation Photosynthesis and Energy (SCOPE) model to explore the potential of ground-based SIF to track Vcmax variability for a subtropical evergreen mixed forest. Then, SIF-derived Vcmax was used to parameterize Boreal Ecosystem Production Simulator (BEPS) model to simulate the GPP. With retrieved vegetative parameters and FQEs, the ground-based SIF was strongly correlated with the model-based SIF simulation at O2-B and O2-A bands, demonstrating that the coefficient of determination (R2) improved from 0.15 (constant values) to 0.60 (retrieved values) for SIFB and from 0.79 to 0.94 for SIFA simulation. Using SIF-derived Vcmax, the R2 value of simulated GPP against eddy covariance-based measurements substantially increased from 0.18 (constant Vcmax) to 0.38 (SIF-derived Vcmax) for dry season and from 0.56 to 0.67 for wet season respectively. The utilization of SIF-derived Vcmax with its corrected temperature response function reduced the relative error in annual GPP simulations by 24.9%. Our results support the significant references toward reducing unbiased SIF simulation and highlighting the potential of ground SIF in deriving Vcmax at the site scale for defining forest management options.

To clarify the global status and research hotspots of heavy metal pollution phytoremediation, we used Web of Science, Cite Space software, and VOS viewer to analyse 1123 publications from the period of 2000-2020. Literature categories, research hotpots, and the most prolific publications by country, institution, and author were analysed separately. Around 34% of the articles are contributed from five countries: China (29.37%), India (11.00%), Spain (6.29%), Italy (6.20%), and Pakistan (5.67%). The hot research topic keywords were "diversity", "translocation", and "enhanced phytoremediation". Cadmium was the most highly concerned heavy metal in the phytoremediation. Twenty-three articles were highly cited, and they mainly focused on 1) enhancing the remediation ability of plants in heavy metal contaminated soil by microbial and chemical additives; 2) the molecular effect and mechanism of heavy metals on plant growth and development; 3) discovering novel heavy metal hyper-enriched plants which can remediate mixed heavy metal pollution. From the above analysis, we concluded that the future research directions should be 1) strengthening the plant remediation ability by biochemical means; 2) studying the molecular mechanism underlying heavy metal damage to plants; 3) studying the enrichment principle of plants for heavy metals. The present study provides a further understanding of the trends in phytoremediation of heavy metal pollution, and the data analysed can be used as a guide for future research directions.

Based on daily maximum temperature (Tmax), daily minimum temperature (Tmin) and daily precipitation collected from 1867 meteorological stations in China from 1961 to 2015, the spatiotemporal variations in temperature and precipitation extremes and their associations with large-scale atmospheric and oceanic circulation patterns were analyzed using linear trend analysis, Pearson correlation analysis and Mann-Kendall method. Results indicate that both the maximum Tmin (TNx) and the minimum Tmin (TNn) had increased significantly at rates of 0–0.5 °C and 0.2–1.0 °C per decade respectively in most of China, whereas the trends in the maximum Tmax (TXx) and the minimum Tmax (TXn) were not significant, resulting in a decrease of diurnal temperature range (DTR) at rates of 0–0.7 °C per decade in most of northeastern China, northern China and western China. The percentage changes in TXn and TNn were much higher than those of TXx and TNx. For precipitation indices, simple daily intensity index (SDII) and extremely wet-day precipitation (R99p) had increased at rates of 0.10 mm/day and 2.6 mm per decade respectively, but the trends of maximum 1-day precipitation (Rx1day), maximum 5-day precipitation (Rx5day) and total wet-day precipitation (PRCPTOT) were not significant in China. The spatial trends of five precipitation indices were also not significant in almost the whole of China. Higher percentage changes of precipitation indices were mainly appeared in western China. Most of climatic indices had positive correlation with Atlantic multidecadal oscillation (AMO) and negative correlation with East Atlantic/Western Russia (EA/WR). The variations of TXx and TNx were more related to the variability of AMO and EA/WR in China, and those of TXn and TNn were more associated with the Arctic oscillation (AO) in northeastern China, northern China and northern Xinjiang. The variations of precipitation indices were not significantly related to the circulation patterns in the vast majority of China.

The carbon budgets in terrestrial ecosystems in China are strongly coupled with climate changes. Over the past decade, China has experienced dramatic climate changes characterized by enhanced summer monsoon and decelerated warming. However, the changes in the trends of terrestrial net ecosystem production (NEP) in China under climate changes are not well documented. Here, we used three ecosystem models to simulate the spatiotemporal variations in China's NEP during 1982–2010 and quantify the contribution of the strengthened summer monsoon and warming hiatus to the NEP variations in four distinct climatic regions of the country. Our results revealed a decadal-scale shift in NEP from a downtrend of –5.95 Tg C/yr2 (reduced sink) during 1982–2000 to an uptrend of 14.22 Tg C/yr2 (enhanced sink) during 2000–10. This shift was essentially induced by the strengthened summer monsoon, which stimulated carbon uptake, and the warming hiatus, which lessened the decrease in the NEP trend. Compared to the contribution of 56.3% by the climate effect, atmospheric CO2 concentration and nitrogen deposition had relatively small contributions (8.6 and 11.3%, respectively) to the shift. In conclusion, within the context of the global-warming hiatus, the strengthening of the summer monsoon is a critical climate factor that enhances carbon uptake in China due to the asymmetric response of photosynthesis and respiration. Our study not only revealed the shift in ecosystem carbon sequestration in China in recent decades, but also provides some insight for understanding ecosystem carbon dynamics in other monsoonal areas.

Remote sensing (RS) technologies provide robust techniques for quantifying net primary productivity (NPP) which is a key component of ecosystem production management. Applying RS, the confounding effects of carbon consumed by livestock grazing were neglected by previous studies, which created uncertainties and underestimation of NPP for the grazed lands. The grasslands in Xinjiang were selected as a case study to improve the RS based NPP estimation. A defoliation formulation model (DFM) based on RS is developed to evaluate the extent of underestimated NPP between 1982 and 2011. The estimates were then used to examine the spatiotemporal patterns of the calculated NPP. Results show that average annual underestimated NPP was 55.74 gC·m-2yr-1 over the time period understudied, accounting for 29.06% of the total NPP for the Xinjiang grasslands. The spatial distribution of underestimated NPP is related to both grazing intensity and time. Data for the Xinjiang grasslands show that the average annual NPP was 179.41 gC·m-2yr-1, the annual NPP with an increasing trend was observed at a rate of 1.04 gC·m-2yr-1 between 1982 and 2011. The spatial distribution of NPP reveals distinct variations from high to low encompassing the geolocations of the Tianshan Mountains, northern and southern Xinjiang Province and corresponding with mid-mountain meadow, typical grassland, desert grassland, alpine meadow, and saline meadow grassland types. This study contributes to improving RS-based NPP estimations for grazed land and provides a more accurate data to support the scientific management of fragile grassland ecosystems in Xinjiang.

Terrestrial ecosystems provide multiple services interacting in complex ways. However, most ecosystem services (ESs) models (e.g., InVEST and ARIES) ignored the relationships among ESs. Process‐based models can overcome this limitation, and the integration of ecological models with remote sensing data could greatly facilitate the investigation of the complex ecological processes. Therefore, based on the Carbon and Exchange between Vegetation, Soil, and Atmosphere (CEVSA) models, we developed a process‐based ES model (CEVSA‐ES) integrating remotely sensed leaf area index to evaluate four important ESs (i.e., productivity provision, carbon sequestration, water retention, and soil retention) at annual timescale in China. Compared to the traditional terrestrial biosphere models, the main innovation of CEVSA‐ES model was the consideration of soil erosion processes and its impact on carbon cycling. The new version also improved the carbon‐water cycle algorithms. Then, the Sobol and DEMC methods that integrated the CEVSA‐ES model with nine flux sites comprising 39 site‐years were used to identify and optimize parameters. Finally, the model using the optimized parameters was validated at 26 field sites comprising 135 site‐years. Simulation results showed good fits with ecosystem processes, explaining 95%, 92%, 76%, and 65% interannual variabilities of gross primary productivity, ecosystem respiration, net ecosystem productivity, and evapotranspiration, respectively. The CEVSA‐ES model performed well for productivity provision and carbon sequestration, which explained 96% and 81% of the spatial‐temporal variations of the observed annual productivity provision and carbon sequestration, respectively. The model also captured the interannual trends of water retention and soil erosion for most sites or basins.

Biomass temporal stability plays a key role in maintaining sustainable ecosystem functions and services of grasslands, and climate change has exerted a profound impact on plant biomass. However, it remains unclear how the community biomass stability in alpine meadows responds to changes in some climate factors (e.g., temperature and precipitation). Long-term field aboveground biomass monitoring was conducted in four alpine meadows (Haiyan [HY], Henan [HN], Gande [GD], and Qumalai [QML]) on the Qinghai-Tibet Plateau. We found that climate factors and ecological factors together affected the community biomass stability and only the stability of HY had a significant decrease over the study period. The community biomass stability at each site was positively correlated with both the stability of the dominant functional group and functional groups asynchrony. The effect of dominant functional groups on community stability decreased with the increase of the effect of functional groups asynchrony on community stability and there may be a 'trade-off' relationship between the effects of these two factors on community stability. Climatic factors directly or indirectly affect community biomass stability by influencing the stability of the dominant functional group or functional groups asynchrony. Air temperature and precipitation indirectly affected the community stability of HY and HN, but air temperature in the growing season and nongrowing season had direct negative and direct positive effects on the community stability of GD and QML, respectively. The underlying mechanisms varied between community composition and local climate conditions. Our findings highlighted the role of dominant functional group and functional groups asynchrony in maintaining community biomass stability in alpine meadows and we highlighted the importance of the environmental context when exploring the stability influence mechanism. Studies of community stability in alpine meadows along with different precipitation and temperature gradients are needed to improve our comprehensive understanding of the mechanisms controlling alpine meadow stability.

Large-scale COVID-19 vaccinations are currently underway in many countries in response to the COVID-19 pandemic. Here, we report, besides generation of neutralizing antibodies, consistent alterations in hemoglobin A1c, serum sodium and potassium levels, coagulation profiles, and renal functions in healthy volunteers after vaccination with an inactivated SARS-CoV-2 vaccine. Similar changes had also been reported in COVID-19 patients, suggesting that vaccination mimicked an infection. Single-cell mRNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) before and 28 days after the first inoculation also revealed consistent alterations in gene expression of many different immune cell types. Reduction of CD8+ T cells and increase in classic monocyte contents were exemplary. Moreover, scRNA-seq revealed increased NF-κB signaling and reduced type I interferon responses, which were confirmed by biological assays and also had been reported to occur after SARS-CoV-2 infection with aggravating symptoms. Altogether, our study recommends additional caution when vaccinating people with pre-existing clinical conditions, including diabetes, electrolyte imbalances, renal dysfunction, and coagulation disorders.

Alpine grasslands play important functions in mitigating climate change and regulating water resources. However, the spatiotemporal variability of their carbon and water budgets remains unquantified. Here, 47 site-year observations of CO

Land use and land cover (LULC) change influences many issues such as the climate, ecological environment, and economy. In this study, the LULC transitions in the Yellow River Basin (YRB) were analyzed based on the GlobeLand30 land use data in 2000, 2010, and 2020. The intensity analysis method with hypothetical errors calculation was used, which could explain the deviations from uniform land changes. The strength of the evidence for the deviation was revealed even though the confusion matrixes of the LULC data at each time point for the YRB were unavailable. The results showed that at the interval scale, the land transition rate increased from the first to the second period for all of the upper, middle, and lower reaches. The exchange component was larger than the quantity and shift component, and the gross change was 4.1 times larger than the net change. The size of cultivated land decreased during both intervals. The artificial surfaces gains were active for all three reaches and had strong evidence. A hypothetical error in 93% of the 2000 data and 58% of the 2010 data can explain deviations from uniform transition given woodland gain during 2000&ndash, 2010 and 2010&ndash, 2020. Ecological restoration projects such as Grain for Green implemented in 2000 in the upper reaches resulted in the woodland increase.

Parkinson's disease (PD) is a common neurodegenerative disease with movement and balance impairments. Although studies have reported improvement of motor symptoms with physical exercise, the mechanisms by which exercise is beneficial remains poorly understood. Our study addresses the exercise-induced changes to peripheral immune cells by interrogating the transcriptome of blood-derived leukocytes in PD patients before and after exercise. Patients attended 1 h exercise classes twice a week for 12 weeks. Leukocytes were collected at the beginning and end of the study for gene expression analysis by RNA-seq or quantitative real-time PCR. We correlated differentially expressed genes after exercise with clinical measures and analyzed the potential functions of gene changes with Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology analysis. Exercise improved measures of movement and balance when compared with scores before the exercise program. Among the gene changes, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis suggests that T-cell receptor signaling, T-cell activation, and T-cell migration pathways were downregulated, while the T-cell receptor signaling pathway was the most significantly correlated with clinical measures. To further investigate T-cell-related changes in PD leukocytes, we reanalyzed the differentially expressed genes from publicly available microarray data and found that genes in the T-cell activation, differentiation, and migration pathways were upregulated in PD samples compared to controls in a time-dependent manner. Together, our findings suggest that exercise rehabilitation may improve movement and balance in PD patients by reversing the upregulated T-cell activation pathways associated with PD. This study was registered with the Chinese Clinical Trial Registry under ChiCTR-TRC-14004707. Registered on May 27, 2014.

Promoting sustainability of ecosystems and economic development is a dual national objective in China, as well as one of the sustainable development goals (SDGs) of the United Nations. The Three-River Headwaters Region, where a National Park initiative has been initiated in the pastoral region of the Qinghai-Tibetan Plateau, is one of the key pilot projects in China with sustainability targets for 2025 and 2035. This paper assesses the possibility of achieving established targets for the proportion of cultivated to available grassland. These targets consider both ecosystem protection and herders’ livelihoods. An income simulation model was first developed to estimate the percentage of cultivated grassland area necessary from the natural grasslands to achieve the target income. The model was developed using income and livestock data from the annual yearbook for 2018, then applied to estimate conditions for three counties in the eastern region. Presently the rangelands are seriously overgrazed with income just reaching above the poverty level. If livestock were decreased to a theoretical carrying capacity level, income would decrease to lower than the poverty level, even considering a livestock feeding system to achieve higher production levels. Under these circumstances, in order to reach income targets in 2025, one option centered on income production from livestock requires 5% of grasslands to be cultivated to produce forage for livestock. However, achieving income targets in 2035 will become very difficult because the needed proportion was estimated to increase to 14%. An alternative was to transport extra forage from the agriculture region of eastern Qinghai province. The local government should consider these two options to improve herders’ income along with maintaining the traditional nomadic culture and sustainable ecosystems. The approach used to develop and apply this model could be applied to predict income changes accompanying future climate scenarios and to propose policies aimed at sustainability of ecosystems and economies for grasslands worldwide.

Accurate and periodic assessment of grassland yield (GY) is of great importance for the management of high altitude plateau grasslands. The Tibetan Plateau (TP) is a very important pastoral area that provides a microcosm of typical alpine grassland ecosystems. Based on remote sensing data, meteorological datasets and observational plant biomass data, we used the Global Production Efficiency Model and Soil and Atmosphere Model (GLOPEM-CEVSA) to estimate GY and its response to climate change and anthropogenic activities on the TP from 1988 to 2013. We quantitatively analyzed spatiotemporal dynamic changes of GY for four geomorphological divisions and five main grassland types. For the 26 years of the study, average annual total GY was 515.8 kg/ha/yr and gradually decreased from the southeast to the northwest of the TP. Annual GY fluctuated from year to year but had an overall positive trend (4.2 kg/ha/yr). Spatiotemporal variation of GY was greatly influenced by spatial heterogeneity. For the total area, the proportion showing a significant increase in GY was 45.2%, while only 12.6% showed a significant decrease. For the main grassland types, GY of Alpine Meadow was highest and had the highest slope of increase. The pattern of decrease of GY from the southeast to the northwest was predominantly related to climate gradients. Regional correlation analysis indicated that warming temperature promoted positive increase of GY for almost all the region. Annual precipitation was related to a less significant decreasing trend of GY over all the TP apart from an increase of GY in the middle area of the north. The grazing pressure index decreased over the years by control of livestock numbers, the reduction of grazing pressure assisting restoration of alpine grasslands. However, grazing pressure on the TP in 2013 remained too high and overloaded. Nevertheless, grassland protection and restoration projects have mitigated grassland degradation in some areas, promoted grassland restoration, and increased incomes of herdsmen. The study indicates that continuation of these projects is critical for the restoration and sustainable use of the TP grasslands.

The maintenance and improvement of ecosystem services on the Tibet Plateau are critical for national ecological security in China and are core objectives of ecological conservation in this region. In this paper, ecosystem service benefits of the Tibet Ecological Conservation Project were comprehensively assessed by estimating and mapping the spatiotemporal variation patterns of critical ecosystem services on the Tibet Plateau from 2000 to 2015. Furthermore, we linked the benefit assessment to the sustainable spatial planning of future ecological conservation strategies. Comparing the 8 years before and after the project, the water retention and carbon sink services of the forest, grassland and wetland ecosystems were slightly increased after the project, and the ecosystem sand fixation service has been steadily enhanced. The increasing forage supply service of grassland significantly reduced the grassland carrying pressure and eased the conflict between grassland and livestock. However, enhanced rainfall erosivity occurred due to increased rainfall, and root-layer soils could not recover in a short period of time, both factors have led to a decline in soil conservation service. The warm and humid climate is beneficial for the restoration of ecosystems on the Tibet Plateau, and the implementation of the Tibet Ecological Conservation Project has had a positive effect on the local improvement of ecosystem services. A new spatial planning strategy for ecological conservation was introduced and aims to establish a comprehensive, nationwide system to protect important natural ecosystems and wildlife, and to promote the sustainable use of natural resources.

Frequent EI Nino events have worldwide impacts, but their effects on carbon and water budgets in alpine grasslands have been poorly explored. The responses of carbon and water vapor exchanges, monitored by the eddy covariance techniques, to the strongest EI Nino event in 2015/2016 were investigated over a humid alpine meadow on the Northeastern Qinghai-Tibetan Plateau. Monthly air temperature (Ta) in August could be considered as a clear indicator of this event and was elevated by 44% (by 4.0 °C) in 2016, mainly due to a 204% (5.2 °C) increase in daily minimum Ta. On a diurnal scale, a paired-samples T-test between the EI Nino duration (August in 2016) and the reference period (August in 2014 and 2015) revealed that the EI Nino-induced increase in gross primary production (GPP, 0.078 gC·m−2·h−1) was lower than the growth in ecosystem respiration (RES, 0.12 gC·m−2·h−1), resulting in an increase in net ecosystem CO2 exchange (NEE, 0.079 gC·m−2·h−1). Diurnal evapotranspiration (ET) was significantly increased, by 8.6%, at a rate of 0.011 mm·h−1. On a monthly scale, this ecosystem fixed less carbon by 58.7 g C·m−2·month−1 while ET water losses increased by only 6.2 mm·month−1 in August. The alpine meadow thus acted as a carbon sink with a 36.2 g C·m−2·year−1 influx in 2015, but switched to a carbon source with a 21.6 g C·m−2·year−1 efflux in 2016, mainly due to a 78.7 g C·m−2·year−1 increase in RES. Annual ET increased by less 3%. The divergent responses of CO2 and H2O fluxes were mostly attributed to a great increase only in nocturnal Ta, which instantaneously stimulated RES but not ET. Our findings revealed that extreme nocturnal warming led to greater carbon losses and weaker compensatory carbon gains, highlighting the inconsistent response of carbon dynamics to gradual warming and to exceptional warmth in humid alpine meadows.

Citrus orchard planting is a typical land-use change process that can impact terrestrial ecosystem services both locally and globally. Long-term monitoring of citrus orchard dynamics is critical fo...

Until 2015, China had established 2740 nature reserves with a total area of 1.47 million km2, covering 14.8% of China’s terrestrial land surface. Based on remote sensing inversion, ecological model simulation and spatial analysis methods, we analyzed the spatial and temporal variations of fractional vegetation coverage (FVC), net primary production (NPP), and human disturbance (HD) in habitats of typical national nature reserves (NNRs) during the first 15 years of the 21st century from 2000 to 2015. And then the three indicators were compared between different NNR types and varied climate zones. The results showed that (1) the average 5-year FVC of NNRs increased from 36.3% to 37.1%, and it improved in all types of NNRs to some extent. The annual average FVC increased by 0.11%, 0.84%, 0.21%, 0.09%, 0.11% and 0.08% in NNRs of forest ecosystem, plain meadow, inland wetland, desert ecosystem, wild animal and wild plant, respectively. (2) The NPP annually increased by 2.06 g·m-2, 1.23 g·m-2, 0.28 g·m-2 and 0.4 g·m-2 in NNRs of plain meadow, inland wetland, desert ecosystem and wild animal, respectively. However, it decreased by 3.45 g·m-2 and 2.35 g·m-2 in NNRs of forest ecosystem and wild plant respectively. (3) In the past 15 years, besides the slight decreases in the NNRs located at the Qinghai-Tibet Plateau and the south subtropical zone, HD enhanced in most of NNRs, especially HD in the warm temperate humid zone increased from 4.7% to 5.35%.

Monitoring and evaluating ecological quality and changes are crucial for policy formulation to guide ecosystem management and socioeconomic sustainable development. However, evaluation of ecological quality is still very challenging due to difficulties in determination of its associated indicators and weights. This paper proposes supporting, providing and regulating ecosystems services-based indicators to describe ecological quality, and applies a Projection Pursuit Model to eliminate redundant indicators and objectively determine weights for an ecological quality index (EQI) on a regional scale. Taking Jiangxi Province, China, as a demonstration area, the data for indicator measures were retrieved from satellite remote sensing and ecosystem modelling with a spatial resolution of 1 km for the three years 2005, 2010 and 2015. The results suggest that Normalized Difference Vegetation Index (NDVI) and water use efficiency (WUE) should be weighed higher and leaf area index (LAI) and Bowen ratio should be weighed lowest in the calculation of an EQI for Jiangxi Province. For 2015, the regional EQI was calculated to be 55.32 on a scale from 0 as the worst to 100 as the best, with higher values ascribed to the hills and mountains and the lower values existing near urban areas. The EQI increased from 52.26 in 2005 to 55.32 in 2015 with an increased area of good-and-above grade from 25.47% to 36.8% for the whole province. The changes in EQI could be attributed to a warmer and wetter climate trend playing a positive dominant effect, while urbanization and afforestation have negative and positive effects, respectively. This study demonstrates that it is feasible to evaluate ecological quality based on a comprehensive set of indicators and PPM-based weight determination, which could be further applied in regular ecological quality monitoring and evaluation on the regional, or even the national scale.

Alpine grasslands play important functions in mitigating climate change and regulating water resources. However, the spatiotemporal variability of their carbon and water budgets remains unquantified. Here, 47 site-year observations of CO2 and water vapor fluxes (ET) are analyzed at sites situated along a hydrothermal gradient across the Qinghai-Tibetan Plateau, including an alpine wetland (wettest), an alpine shrub (coldest), an alpine meadow, an alpine meadow-steppe, and an alpine steppe (driest and warmest). The results show that the benchmarks for annual net ecosystem exchange (NEE) are −79.3, −77.8, −66.7, 20.2, and 100.9 g C m−2 year−1 at the meadow, shrub, meadow-steppe, steppe, and wetland, respectively. The peak daily NEE normalized by peak leaf area index converges to 0.93 g C m−2 d−1 at the 5 sites. Except in the wetland (722.8 mm), the benchmarks of annual ET fluctuate from 511.0 mm in the steppe to 589.2 mm in the meadow. Boosted regression trees-based analysis suggests that the enhanced vegetation index (EVI) and net radiation (Rn) determine the variations of growing season monthly CO2 fluxes and ET, respectively, although the effect is to some extent site-specific. Inter-annual variability in NEE, ecosystem respiration (RES), and ET are tightly (R2 > 0.60) related to the inter-growing season NEE, RES, and ET, respectively. Both annual RES and annual NEE are significantly constrained by annual gross primary productivity (GPP), with 85% of the per-unit GPP contributing to RES (R2 = 0.84) and 15% to NEE (R2 = 0.12). Annual GPP significantly correlates with annual ET alone at the drier sites of the meadow-steppe and the steppe, suggesting the coupling of carbon and water is moisture-dependent in alpine grasslands. Over half of the inter-annual spatial variability in GPP, RES, NEE, and ET is explained by EVI, atmospheric water vapor, topsoil water content, and bulk surface resistance (rs), respectively. Because the spatial variations of EVI and rs are strongly regulated by atmospheric water vapor (R2 = 0.48) and topsoil water content (R2 = 0.54), respectively, we conclude that atmospheric water vapor and topsoil water content, rather than the expected air/soil temperatures, drive the spatiotemporal variations in CO2 fluxes and ET across temperature-limited grasslands. These findings are critical for improving predictions of the carbon sequestration and water holding capacity of alpine grasslands.

Permafrost degradation due to climate warming would potentially increase the release of previously frozen soil carbon and change the carbon budget of the cold region ecosystem. The underlying permafrost degradation would be effectively mediated by soil surface freezing-thawing (FT) processes. Aboveground vegetation can regulate soil FT processes, however its effects on ground thermal transfer have not been well represented by ecosystem models. In this study, we improved the hydrothermal module of the Boreal Ecosystem Productivity Simulator (BEPS) through more careful parameterization of snowpack density, puddled water, soil organic matter and super-cooled soil water. The impacts of vegetation on the soil surface FT processes have also been investigated using the improved BEPS model and the measured soil temperature data at forest and grassland sites on the southern edge of permafrost region in Mongolia and northeastern China. The improved BEPS model performs better than the original model in simulations of soil temperature and soil FT processes. Smaller amplitudes of soil diurnal FT cycles were found in forest sites compared to grassland sites. Forest sites have delayed soil thaw timing and similar soil freezing time compared to grassland sites. Differences in snow depths and soil organic matter content due to distinct vegetation community structures have considerable influences on the disparity in soil FT processes. Thus, it is important to improve the simulation of the impacts of vegetation on soil surface FT processes for better forecasting the permafrost degradation.

Solar-induced chlorophyll fluorescence (SIF) is considered as a prospective indicator of vegetation photosynthetic activity and the ecosystem carbon cycle. The current coarse spatial-temporal resolutions of SIF data from satellite missions and ground measurements still cannot satisfy the corroboration of its correlation with photosynthesis and carbon flux. Practical approaches are needed to be explored for the supplementation of the SIF measurements. In our study, we clarified the diurnal variations of leaf and canopy chlorophyll fluorescence for a subtropical evergreen coniferous forest and evaluated the performance of the canopy chlorophyll concentration (CCC) approach and the backward approach from gross primary production (GPP) for estimating the diurnal variations of canopy SIF by comparing with the Soil Canopy Observation Photosynthesis Energy (SCOPE) model. The results showed that the canopy SIF had similar seasonal and diurnal variations with the incident photosynthetically active radiation (PAR) above the canopy, while the leaf steady-state fluorescence remained stable during the daytime. Neither the CCC nor the raw backward approach from GPP could capture the short temporal dynamics of canopy SIF. However, after improving the backward approach with a correction factor of normalized PAR incident on leaves, the variation of the estimated canopy SIF accounted for more than half of the diurnal variations in the canopy SIF (SIF687: R2 = 0.53, p &lt, 0.001, SIF760: R2 = 0.72, p &lt, 0.001) for the subtropical evergreen coniferous forest without water stress. Drought interfered with the utilization of the improved backward approach because of the decoupling of SIF and GPP due to stomatal closure. This new approach offers new insight into the estimation of diurnal canopy SIF and can help understand the photosynthesis of vegetation for future climate change studies.

Background: Relapse due to loss of the CD19 targeted epitope presents a therapeutic challenge of CD19 CAR-T therapy. These patients universally have poor outcomes. CD20 is a proven therapeutic target for B-Cell Non-Hodgkin Lymphomas (B-NHL), supported by previously approved and widely used monoclonal antibody therapy. C-CAR066 is a novel 2nd generation chimeric antigen receptor T (CAR-T) therapy. Preclinical studies suggest that C-CAR066 has superior anti-tumor activity compared to CAR-Ts derived from scFVs of Leu16, Rituximab, and Obinutuzumab, Methods: NCT04036019 is a single arm, single-center, non-randomized phase I clinical trial conducted at Shanghai Tongji Hospital to evaluate the safety and efficacy of C-CAR066 in subjects with r/r B cell lymphoma who were previously treated with anti-CD19 CAR-T therapy. The primary objective of the study is to evaluate incidence and severity of treatment emergent adverse events. The secondary objectives include determining overall response rate (ORR), PFS, and OS. C-CAR066 is manufactured in a serum free, semi-automated, and digitally closed system. C-CAR066 is administered to patients as a single intravenous dose after a standard 3-day cyclophosphamide/fludarabine conditioning regimen. Results: As of Aug 3, 2020, 7 patients (all DLBCL) were enrolled and infused with C-CAR066 with a dose range of 2.0 x 106 to 5.0 x 106 CAR-T cells. The manufacturing success rate was 100%. All patients had relapsed after anti-CD19 CAR-T treatment, only one of the patients had achieved CR following anti-CD-19 CAR-T therapy. C-CAR066 treatment was well tolerated with reversible grade 1~2 CRS in six patients, grade 3 CRS in another patient, and no neurotoxicity events. 6/7 patients showed clinical improvement (best overall response rate, BOR = 85.7%). The best overall responses include 3 CR and 3PR. All patients responded to C-CAR066 treatment and showed different degrees of tumor regression (45-100%). Furthermore, the expansion and proliferation of C-CAR066 CAR-T cells in the peripheral blood positively correlated with the extent of tumor regression. Conclusion: C-CAR066 has a favorable safety profile and shows promising early efficacy in patients with r/r NHL following CD19 CAR-T therapy. It confirms that C-CAR066 has a different mechanism of action compared to anti-CD-19 CAR-T therapy. These data provide strong scientific rationale to the strategy of targeting both CD20 and CD19 tumor antigens and to ask whether this leads to superior clinical benefit to targeting either CD19 or CD20 alone in NHL. Disclosures Huang: Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zhu:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Yao:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zhu:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zheng:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Chen:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Lan:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Chen:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Wei:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Shu:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Ye:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zhang:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Wang:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Hong:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Ren:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zhang:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Humphries:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Yao:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.

Mantle cell lymphoma (MCL) is a distinct histological type of B-cell lymphoma with a poor prognosis. Several agents, such as proteasome inhibitors, immunomodulatory drugs, and inhibitors of B cell lymphoma-2 and Bruton's tyrosine kinase have shown efficacy for relapsed or refractory (r/r) MCL but often have short-term responses. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a novel treatment modality for r/r non-Hodgkin's lymphoma. However, long-term safety and tolerability associated with CAR T-cell therapy are not defined well, especially in MCL. In this report, we described a 70-year-old patient with r/r MCL with 48-month duration of follow-up who achieved long-term remission after CAR T-cell therapy. CAR T-cell-related toxicities were also mild and tolerated well even in this elderly patient. This report suggested that CAR T-cell therapy is a promising treatment modality for patients with MCL, who are generally elderly and have comorbid conditions.

Factors associated with complete and durable remissions after anti-CD19 chimeric antigen receptor T (CAR-T) cell immunotherapy for relapsed or refractory non-Hodgkin lymphoma (r/r NHL) have not been well characterized. In this study, we found that the different sites of extranodal involvement may affect response, overall survival (OS), and progression-free survival (PFS) in patients with r/r NHL treated with anti-CD19 CAR-T cells. In a cohort of 32 treated patients, 12 (37.5%) and 8 (25%) patients exhibited soft tissue lymphoma and bone marrow (BM) infiltrations, respectively, and 13 (41%) patients exhibited infiltration at other sites. The factors that may affect prognosis were identified through multivariable analysis. As an independent risk factor, soft tissue infiltration was the only factor significantly correlated with adverse prognosis (P < 0.05), whereas other factors did not reach statistical significance. Furthermore, the site of extranodal tumor infiltration significantly and negatively affected OS and PFS in patients with r/r NHL treated with anti-CD19 CAR-T cell therapy. PFS and OS in patients with BM involvement were not significantly different from those of patients with lymph node involvement alone. Thus, anti-CD19 CAR-T cell therapy may improve the prognosis of patients with BM infiltration.

Alpine ecosystems play an important role in the global carbon cycle, yet the long-term response of in situ ground-based observations of carbon fluxes to climate change remains not fully understood. Here, we analyzed the continuous net ecosystem CO2 exchange (NEE) measured with the eddy covariance technique over an alpine Potentilla fruticosa shrubland on the northeastern Qinghai-Tibetan Plateau from 2003 to 2012. The shrubland acted as a net CO2 sink with a negative NEE (-74.4 +/- 12.7 g C m(-2) year(-1), Mean +/- S.E.). The mean annual gross primary productivity (GPP) and annual ecosystem respiration (RES) were 511.8 +/- 11.3 and 437.4 +/- 17.8 g Cm-2 year(--1), respectively. The classification and regression trees (CART) analysis showed that aggregated growing season degree days (GDD) was the predominant determinant on variations in monthly NEE and monthly GPP, including its effect on leaf area index (LAI, satellite-retrieved data). However, variations in monthly RES were determined much more strongly by LAI. Non-growing season soil temperature (T-s) and growing season length (GSL) accounted for 59% and 42% of variations in annual GPP and annual NEE, respectively. Growing season soil water content (SWC) exerted a positive linear influence on variations in annual RES (r(2) = 0.40, p = 0.03). The thermal conditions and soil water status during the onset of the growing season are crucial for inter-annual variations of carbon fluxes. Our results suggested that an extended growing season and warmer non-growing season would enhance carbon assimilation capacity in the alpine shrubland. (C) 2016 Elsevier B.V. All rights reserved.

This work addressed the inter-calibration of the two split-window channels 4 and 5 IR4, around 10.8 µm; IR5, around 12.0 µm of Visible and Infrared Radiometer VIRR aboard FengYun 3 FY-3 A and B satellites against the hyperspectral channels of Atmospheric Infrared Sounder AIRS on Aqua and Infrared Atmospheric Sounding Interferometer IASI on Metop-A over the Arctic area 180oW–180oE, 60oN–90oN using the hyperspectral convolution HSC method in June and December of 2010–2013. First, the satellite data were re-sampled into the gridded study area using the area-weighted pixel-aggregation method. Then, besides the collocation condition, the measurements acquired by different instruments were matched with the following criteria: 1 the absolute observation time difference is less than 20 min |∆time|< 20ʹ, and 2 |cosθ1 /cosθ2 – 1|< 0.015, where θ1 and θ2 are the at-surface view zenith angles VZAs of the VIRR/FY-3 measurement and the hyperspectral measurement, respectively. Finally, linear regression analyses on the matching measurements were carried out to obtain the inter-calibration coefficients, and re-calibrated VIRR/FY-3A/B measurements were achieved. The results showed that the calibrations of AIRS/Aqua and IASI/Metop-A channels were quiet consistent, whereas, against the hyperspectral channels, the calibrations of VIRR/FY-3A/B channels 4 and 5 were biased, and they presented certain seasonal and annual variations, especially for VIRR/FY-3A channel 4. In contrast to VIRR/FY-3A channels, the calibration discrepancies of VIRR/FY-3B channels 4 and 5 were smaller. Moreover, no obvious impact of solar illumination on VIRR/FY-3A/B measurements was observed.

Inspired by concerns of the effects of a warming climate, drought variation and its impacts have gained much attention in China. Arguments about China's drought persist and little work has utilized agricultural drought survey area to evaluate the impact of natural drought on agriculture. Based on a newly revised self-calibrating Palmer Drought Severity Index (PDSI) model driven with air-relative-humidity-based two-source (ARTS) E0 (PDSIARTS; Yan et al., 2014), spatial and temporal variations of drought were analyzed for 1982–2011 in China, which indicates that there was nonsignificant change of drought over this interval but with an extreme drought event happened in 2000–2001. However, using air temperature (Ta)-based Thornthwaite potential evaporation (EP_Th) and Penman-Monteith potential evaporation (EP_PM) to drive the PDSI model, their corresponding PDSITh and PDSIPM all gave a significant drying trend for 1982–2011. This suggests that PDSI model was sensitive to EP parameterization in China. Annual drought-covered area from agriculture survey was initially adopted to evaluate impact of PDSI drought on agriculture in China during 1982–2011. The results indicate that PDSIARTS drought area (defined as PDSIARTS

The mammalian brain is heterogeneous, containing billions of neurons and trillions of synapses forming various neural circuitries, through which sense, movement, thought, and emotion arise. The cellular heterogeneity of the brain has made it difficult to study the molecular logic of neural circuitry wiring, pruning, activation, and plasticity, until recently, transcriptome analyses with single cell resolution makes decoding of gene regulatory networks underlying aforementioned circuitry properties possible. Here we report success in performing both electrophysiological and whole-genome transcriptome analyses on single human neurons in culture. Using Weighted Gene Coexpression Network Analyses (WGCNA), we identified gene clusters highly correlated with neuronal maturation judged by electrophysiological characteristics. A tight link between neuronal maturation and genes involved in ubiquitination and mitochondrial function was revealed. Moreover, we identified a list of candidate genes, which could potentially serve as biomarkers for neuronal maturation. Coupled electrophysiological recording and single cell transcriptome analysis will serve as powerful tools in the future to unveil molecular logics for neural circuitry functions. Electronic supplementary material The online version of this article (doi:10.1007/s13238-016-0247-8) contains supplementary material, which is available to authorized users.

Background: Aiming to improve both the response rate and durability of response while limiting antigen escape of CD-19 following anti-CD-19 CAR-T therapy, C-CAR039 has been developed as a 2nd generation 4-1BB novel bi-specific chimeric antigen receptor T (CAR-T) therapy targeting both CD19 and CD20 antigens. Methods: NCT04317885 is a single arm, single-center, non-randomized phase I clinical trial designed to evaluate the safety and efficacy of C-CAR039 in treatment of relapsed or refractory NHL (r/r NHL) patients. The primary objective of the study is to evaluate incidence and severity of treatment emergent adverse events. The secondary objectives include determining overall response rate (ORR), progression-free survival, and overall survival. Results: In preclinical studies, human T cells transduced with the lentiviral vector encoding C-CAR039in vitroshowed CAR-T proliferation, cytokine production, cytotoxicity to CD19, and CD20 single positive and double positive tumor cells. C-CAR039 can eradicate CD19/CD20 positive tumor cellsin vivobased on our animal model study. A Phase 1 trial was conducted in Shanghai Tongji Hospital in patients with r/r NHL to assess the safety and efficacy of C-CAR039 (NCT04317885). Following apheresis to harvest T cells, C-CAR039 was manufactured and infused as a single intravenous dose after a standard 3-day cyclophosphamide/fludarabine conditioning regimen. C-CAR039 was manufactured in a serum free, semi-automated, and digitally closed system with median vein to vein time of 18 days. The manufacturing success rate was 100%. As of Aug 3, 2020, 16 patients were infused with C-CAR039 with a dose range of 1.0 x 106 to 5.0 x 106 CAR-T cells/kg. 14 patients had at least one-month evaluable safety data and 13 patients (11 DLBCL, 2 FL patients) had one-month or longer efficacy data. C-CAR039 treatment was well tolerated with no grade 3 or higher cytokine release syndrome(CRS) and no neurotoxicity event. Reversible grade 1~2 CRS was observed in 12 (86%) of patients. Cytopenias due to the conditioning regimen were common and reversible. At the one-month evaluation, 12/13 patients showed clinical improvement (ORR=92%) and 11/11 of DLBCL patients responded to the treatment (ORR=100%). Median follow-up was 70 days (range: 35-257 days). The best overall response (BOR) includes 10 complete responses (CRs) and 2 partial responses (PRs). Furthermore, C-CAR039 proliferation and expansion in the peripheral blood positively correlated with tumor regression. Conclusion: C-CAR039 shows promising efficacy and a favorable safety profile in the early clinical trial in patients with r/r NHL. The early clinical efficacy signal is encouraging and compares favorably to anti-CD19 CAR-T therapies. These findings need to be evaluated in more patients with longer follow-up to confirm safety, efficacy and duration of response. Disclosures Huang: Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zhu:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Yao:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zhu:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zheng:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Chen:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Li:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Lan:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Chen:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Guo:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zhang:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zheng:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Wang:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Hong:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Ren:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zhang:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Humphries:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Yao:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.

Tropical rice production is at risk from rising temperature. Understanding regional and seasonal heterogeneity of optimum temperatures for rice production is important for model simulation to predict rice yield change under climate change. However, studies or tools for widely observation of crop responses to temperature over broad spatial scales with long time spans are limited. In this study, we detected optimum temperature range for rice gross primary production ( T opt GPP ) in the lower Gangetic plains and delta region using the near-infrared reflectance of vegetation (NIRV), which is a new photosynthetic proxy, to improve ORYZA model performance in high-temperature season and assessed how tropical rice would respond to temperature increase in the study area. According to satellite observations of NIRV from 2001 to 2015, current ambient air temperature has exceeded the mean T opt GPP of Boro rice (24.8 ± 1.8 °C) and Aman rice (26.7 ± 1.2 °C) in the lower Gangetic plains and delta region, suggesting a downtrend of rice production under future warming. The detection results show that rice has lower T opt GPP in the regions with more drought stress and lower background temperature under water-limited conditions. Furthermore, the model modified by NIRv- T opt GPP shows better performance in potential yields, especially in high-temperature seasons on the region scale. Without CO2 fertilization effect, each degree-Celsius increase is expected to reduce rice potential yields by 4.9 ± 1.6% based on the default T opt GPP range in ORYZA model and by 7.0 ± 1.2% based on the detected NIRv- T opt GPP range in the study area. This study implies that global grid-based model simulation may underestimate sensitivity of tropical rice yield to temperature rise due to the neglect of regional and seasonal heterogeneity of T opt GPP . NIRV makes it possible to determine local optimal temperatures for crop production, and to improve grid-based modelling across various agricultural systems in different growing seasons at the regional scale.

Due to the limitedness of land, the coordinated development of production, living, and ecological (PLE) land is essential for sustainable development. A clear understanding of PLE land change is necessary given the increased human activities, especially in developing regions. This study first reclassified remotely sensed landuse maps in Shandong province into PLE land. Then the spatiotemporal change of PLE land between 2000 and 2015 was analyzed using spatial trajectory and intensity analysis methods. The results show that the rate of PLE land change in the interval of 2000&ndash, 2005 was the highest, and it kept decreasing during 2005&ndash, 2010 and 2010&ndash, 2015. The overall quantity component accounts for more difference than the exchange and shift components for all intervals. At the category level, the largest quantity component of change was PE land loss, followed by LP land gain. LP land gain targeted PE land intensively in each interval. The loss of E land was mainly to PE land in terms of size, and to PL land in terms of intensity. The findings of this study contribute to a deeper understanding of the spatiotemporal transitions of PLE land in Shandong province, which could help policy making for PLE land regulation.