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Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target to reduce lipids. In 2020, we reported a chimeric camelid-human heavy chain antibody VHH-B11-Fc targeting PCSK9. Recently, it was verified that VHH-B11 binds one linear epitope in the PCSK9 hinge region. To enhance its druggability, we have developed a novel biparatopic B11-H2-Fc Ab herein. Thereinto, surface plasmon resonance (SPR) confirmed the epitope differences in binding-PCSK9 among VHH-B11, VHH-H2 and the approved Repatha. Additionally, SPR revealed the B11-H2-Fc exhibits an avidity of approximately 0.036 nM for PCSK9, representing a considerable increase compared to VHH-B11-Fc (~ 0.69 nM). Moreover, we found the Repatha and B11-H2-Fc exhibited > 95% PCSK9 inhibition efficiency compared to approximately 48% for the VHH-Fc at 7.4 nM (P < 0.0005). Further, we verified its biological activity using the human hepatoma cells G2 model, where the B11-H2-Fc exhibited almost 100% efficiency in PCSK9 inhibition at only 0.75 μM. The immunoblotting results of low-density lipoprotein cholesterol (LDL-c) uptake assay also demonstrated the excellent performance of B11-H2-Fc on recovering the LDL-c receptor (LDLR), as strong as the Repatha (P > 0.05). These findings provide the first evidence of the efficacy of a novel Ab targeting PCSK9 in the field of lipid-lowering drugs. [ABSTRACT FROM AUTHOR]

Aim: Significant changes in species elevational ranges in mountains have been repeatedly documented, yet the direction, magnitude and drivers of these shifts remain controversial. Presently, there is still lacking evidence about the general nature of species elevational range shifts in eastern Eurasia in response to anthropogenic climate change. By using historical specimen records and recent field observations for 735 seed plant species across 29 China's mountains, we assessed changes in species' elevational centroids and their drivers. Location: China. Time Period: 1950–2018. Major Taxa Studied: Seed plant species. Methods: The elevation records of all sampled occurrences in each mountain during the two time periods were estimated, and the null models were developed to test the sampling bias. Ecological niche models (ENMs) were used to evaluate the relative importance of climate factors in constraining each species distribution. Generalized linear models (GLMs) to test the relationships between the centroid elevational range shifts of species and different divers. Results: We found that 54% of the species shifting upward and 46% downhill. However, species' elevational shifts significantly differed among species and mountains. Herbaceous and lowland species moved upward faster than woody and high‐elevation species. Species in temperate mountains and in mountains with taller elevational gradients moved upward, while species in subtropical mountains and in mountains with shorter elevational gradients moved downward. Precipitation changes experienced by species, species' climatic adaptations, several species' functional traits and mountain size all contributed to explain the magnitude of species' centroid elevational range shifts. Main Conclusions: Our results highlight complex biodiversity redistribution of seed plants across Chinese mountains, not necessarily conforming to the trend of species upward shifts in elevation. Changes in precipitation regimes may blur the simplistic assumption of isotherm tracking. This study fills an important geographic shortfall for our understanding of biodiversity redistribution under anthropogenic climate change. [ABSTRACT FROM AUTHOR]

Soil protists play a key role in driving ecological functions through predation and parasitism. However, little is known about how nitrogen (N) deposition and seasonal variation influence soil protist functions in forest soils.Here, we assessed first the impacts of N deposition (control, 50, 100 and 150 kg N ha−1 year−1) on the functional composition of the soil protist community in summer and winter, using amplicon sequencing of environmental DNA from a subtropical natural forest.We found that soil protists were dominated by consumers (42.6%–51.6%), followed by parasites (32.9%–40.9%) and phototrophs (3.2%–13.1%), implying a predominant role of consumers and potential top‐down effects on the other trophic groups in subtropical forest soils. The functional composition of soil protists was greatly influenced by N deposition, but these responses were dependent on seasonal variation. The diversity of phototrophs was lower in summer than in winter. Instead, an opposite pattern was observed for consumers, resulting in a significantly higher protist diversity in summer than in winter. Furthermore, low and high N deposition simplified the structural complexity of soil protist communities, suggesting a nonlinear response of protist structural stability to N deposition.Synthesis and applications. This study provides unprecedented evidence that seasonal variation plays an important role in regulating responses of soil protist functional composition to N deposition, and highlights the nonlinear effects of rising N deposition on the soil food web. [ABSTRACT FROM AUTHOR]

Aims: Nitrogen (N) deposition, as a global environmental threat, has exhibited profound impacts on the nutrient cycling and ecosystem functioning of natural forests. However, little is known about how different N deposition levels influence the diversity, community composition, and structural complexity of the denitrifying bacteria. Methods: Here we set up a field experiment to investigate the impacts of N deposition (0, 50, 100, and 150 kg N ha−1 yr−1) on soil denitrification and underlying mechanisms in a subtropical forest. Results: The denitrifying activity was significantly decreased by the high level of N deposition compared to the control. The abundances of denitrification functional genes were commonly increased by the lower rate of N deposition, while significantly suppressed by the higher levels of N deposition. Non-metric multidimensional scaling ordinations showed that the denitrifier assemblages were evidently clustered based on N deposition levels and soil layers, regardless of sampling seasons. Structural equation modeling analysis indicated that the denitrifier abundance and community composition directly explained 62% of the total variance of denitrifying activity. Soil pH exhibited profound effects on the denitrifier abundance, diversity, and community composition. Nitrogen deposition affected the denitrifier co-occurrence networks with increased complexity under the highest level of N deposition compared to the control. Conclusions: This study emphasized the crucial role of denitrifier community composition in shaping soil denitrifying activity under N deposition, highlighting the importance of incorporating the dynamics of denitrifier communities together with soil environmental parameters into the models for accurately predicting ecosystem processes in forests. [ABSTRACT FROM AUTHOR]

Nitrogen (N) deposition has changed plants and soil microbes remarkably, which deeply alters the structures and functions of terrestrial ecosystems. However, how forest fungal diversity, community compositions, and their potential functions respond to N deposition is still lacking in exploration at a large scale. In this study, we conducted a short-term (4–5 years) experiment of artificial N addition to simulated N deposition in five typical forest ecosystems across eastern China, which includes tropical montane rainforest, subtropical evergreen broadleaved forest, temperate deciduous broadleaved forest, temperate broadleaved and conifer mixed forest, and boreal forest along a latitudinal gradient from tropical to cold temperature zones. Fungal compositions were identified using high-throughput sequencing at the topsoil layer. The results showed that fungal diversity and fungal community compositions among forests varied apparently for both unfertilized and fertilized soils. Generally, soil fungal diversity, communities, and their potential functions responded sluggishly to short-term N addition, whereas the fungal Shannon index was increased in the tropical forest. In addition, environmental heterogeneity explained most of the variation among fungal communities along the latitudinal gradient. Specifically, soil C: N ratio and soil water content were the most important factors driving fungal diversity, whereas mean annual temperature and microbial nutrient limitation mainly shaped fungal community structure and functional compositions. Topsoil fungal communities in eastern forest ecosystems in China were more sensitive to environmental heterogeneity rather than short-term N addition. Our study further emphasized the importance of simultaneously evaluating soil fungal communities in different forest types in response to atmospheric N deposition. [ABSTRACT FROM AUTHOR]

Forest soils represent a major stock of organic carbon (C) in the terrestrial biosphere, but the dynamics of soil organic C (SOC) stock are poorly quantified, largely due to lack of direct field measurements. In this study, we investigated the 20-year changes in SOC stocks in eight permanent forest plots, which represent boreal (1998–2014), temperate (1992–2012), subtropical (1987–2008), and tropical forest biomes (1992–2012) across China. SOC contents increased significantly from the 1990s to the 2010s, mostly in the upper 0–20 cm soil depth, and soil bulk densities do not change significantly during the same period. As a result, the averaged SOC stocks increased significantly from 125.2±85.2 Mg C ha -1 in the 1990s to 133.6±83.1 Mg C ha -1 in the 2010s across the forest plots, with a mean increase of 127.2–907.5 kg C ha -1 yr -1. This SOC accumulation resulted primarily from increasing leaf litter and fallen logs, which accounts 3.6 %–16.3 % of above-ground net primary production. Our findings provided direct evidence that China's forest soils have been acting as significant C sinks, although their strength varies in forests with different climates. [ABSTRACT FROM AUTHOR]

Understanding factors controlling ecosystem structure and function is key to predicting the effects of climate change on vegetation distribution and carbon sequestration. Cyclones play a large role in structuring ecosystems and cyclone intensity is expected to increase on a warming planet. The effects of cyclones on broad-scale ecosystem patterns could be substantial but are poorly understood. This study assessed forest structure and biodiversity patterns across an elevation gradient (300-3000 m) in mountainous, humid forests of Taiwan, an island experiencing an average of 3-6 typhoons (regional name of cyclones) annually, and contrasted those patterns with a gradient within the Wuyi Mountains of China (500-2100 m), where the climate is similar to Taiwan but typhoon occurrence is rare and effects are generally minimal. In both Taiwan and the Wuyi Mountains, tree species richness and diversity decreased with increasing elevation. Tree size and stature decrease from low to high elevations in the typhoon-protected Wuyi Mountains. In contrast, the biomass and stature of forests in Taiwan increased from low to high elevations. The relationship between forest stature and climate was also contrasting in relation to typhoon disturbance in that we found decreasing tree height and basal area with increasing temperature in Taiwan, but not in the Wuyi Mountains. The more than twofold increase in tree height and biomass with increasing elevations reported here for subtropical humid forests of Taiwan is a unique pattern that highlights the potential role of cyclones in driving elevational patterns of forest structure. Climate change-induced alterations in tropical cyclone regimes may affect elevational patterns of forest structure and carbon sequestration in regions experiencing frequent cyclones. [ABSTRACT FROM AUTHOR]

Diversity-manipulation experiments suggest a positive effect of biodiversity on ecosystem properties (EPs), but variable relationships between species richness and EPs have been reported in natural communities. An explanation for this discrepancy is that observed richness-EPs relationships in natural communities change with environment and species functional identities. But how the relationships change along broad-scale climatic gradients has rarely been examined. In this paper, we sampled 848 plots of 20 × 30 m2 from boreal to tropical forests across China. We examined plot biomass with respect to environmental factors, tree species richness and functional group identity (FGI, i.e. evergreen vs deciduous, and coniferous vs broadleaf). Variation partitioning was used to evaluate the relative effects of the three classes of factors. We found that, most of the 'effects' (percentage of variation explained) of richness and FGI on forest biomass were shared with environmental factors, but species richness and FGI still revealed significant effects in addition to environment for plots across China. Richness and FGI explained biomass mainly through their shared effects instead of independent effects, suggesting that the positive biodiversity effect is closely associated with a sampling effect. The relative effects of richness, FGI and environment varied latitudinally: the independent effects of environment and richness decreased from boreal to subtropical forests, whereas the total effect of FGI increased. We also found that the slope of richness-biomass relationship decreased monotonically from boreal to subtropical forests, possibly because of decreasing complementarity and increasing competition with increasing productivity. Our results suggest that while species richness does have significant effects on forest biomass it is less important than environmental gradients and other biotic factors in shaping large-scale biomass patterns. We suggest that understanding how and why the diversity-EPs relationships change along climatic gradient would be helpful for a better understanding of real biodiversity effects in natural communities. [ABSTRACT FROM AUTHOR]

Anthropogenic nitrogen (N) emissions to atmosphere have increased dramatically in China since 1980s, and this increase has aroused great concerns on its ecological impacts on terrestrial ecosystems. Previous studies have showed that terrestrial ecosystems in China are acting as a large carbon (C) sink, but its potential in the future remains largely uncertain. So far little work on the impacts of the N deposition on C sequestration in China’s terrestrial ecosystems has been assessed at a national scale. Aiming to assess and predict how ecological processes especially the C cycling respond to the increasing N deposition in China’s forests, recently researchers from Peking University and their partners have established a manipulation experimental network on the ecological effects of the N deposition: Nutrient Enrichment Experiments in China’s Forests Project (NEECF). The NEECF comprises 10 experiments at 7 sites located from north to south China, covering major zonal forest vegetation in eastern China from boreal forest in Greater Khingan Mountains to tropical forests in Hainan Island. This paper introduces the framework of the NEECF project and its potential policy implications. [ABSTRACT FROM AUTHOR]

Understanding how patterns of biodiversity vary among taxonomic levels can provide insights into the mechanisms that regulate the assembly of ecological communities. In this study, we examined the scale and environmental dependence of the relationship between number of species and number of genera/families in woody plant communities to investigate the influences of species pool and local ecological processes on the taxonomic structures of local communities. The data we used are based on a large number of forest plots collected across the eastern part of China and the globe. The results showed that the ratio of the number of genera/families:species and the taxonomic exponents, i.e. the exponents of the genus/family-species relationship, were generally lower than null expectations based on the regional species pool, suggesting that abiotic filtering (e.g. environmental filtering and dispersal limitation) is more important than interspecific competition in shaping local communities. The extent of species pool and the area sampled for local communities both influenced our ability to infer whether local ecological processes were important. In particular, the deviation of the taxonomic ratios and exponents between empirical and null patterns increased as the extent of species pool increased, and the taxonomic exponents declined as area of the local community increased, due partly to the reduced effect of interspecific competition. We conclude that regional species pools and local processes both influenced the taxonomic structure of local woody plant communities, but their effects vary substantially among spatial scales. [ABSTRACT FROM AUTHOR]

Biodiversity patterns and their underlying mechanisms have long been focal topics of study for ecologists and biogeographers. However, compared with spatial variation in species richness (α- and γ-diversity), β-diversity, or the dissimilarity of species composition between two or more sites has until recently received limited attention. In this study, we explored the large-scale patterns of altitudinal turnover (β-diversity) of plants in montane forests of China, based on systematic inventories of 1153 plots from 46 mountains distributed over ˜30 degrees of latitude (21.9-51.7°N) and ˜4100 m of altitude (160-4250 m). The β-diversity of trees and shrubs declined significantly with increasing latitude. Along the altitudinal gradient, β-diversity of both trees and shrubs showed non-significant trends in most mountains. Differences in climate explained ˜30.0% of the variation in tree β-diversity (27.7, 36.5, and 26.2% for the Jaccard's, βj, Sorenson's, βs, and Simpson's dissimilarity, βsim, respectively), with mean annual temperature being most important, and ≤ 10.0% of that in shrub β-diversity (10.0, 8.2, and 7.0% for βj, βs, and βsim, respectively), with annual actual evapotranspiration and annual precipitation as the main predictors. However, climatic controls of β-diversity varied dramatically in different biogeograpical regions. The β-diversity of trees exhibited stronger, whereas that of shrubs showed weaker, climatic patterns in temperate and arid than subtropical regions. These results suggest that mechanisms causing patterns of β-diversity may differ between latitudinal and altitudinal gradients, and among biogeographical regions; as a result, caution should be exercised in drawing close parallels between patterns and causes of β-diversity along latitudinal and altitudinal gradients and among regions. [ABSTRACT FROM AUTHOR]

Disentangling the relative effects of local and regional processes on local species richness (LSR) is critical for understanding the mechanisms underlying large-scale biodiversity patterns. In this study we used 1098 forest plots from 41 mountains across China, together with regional flora data, to examine the relative influence of local climate vs regional species richness (RSR) on LSR patterns. Both RSR and LSR for woody species and all species combined decreased with increasing latitude, while richness of herbaceous species exhibited a hump-shaped pattern. The major climatic orrelates of species richness differed across spatial scales. At the regional scale, winter coldness was the best predictor of RSR patterns for both woody and herbaceous species. At the local scale, however, productivity-related climatic indices were the best predictors of LSR patterns. Local climate and RSR together explained 48, 54 and 23% of the variation in LSR, for overall, woody and herbaceous species, respectively. Both local climate and RSR independently influenced LSR in addition to their joint effects, suggesting that LSR patterns were shaped by local and regional processes together. Local climate and RSR affected LSR of woody species mainly through their joint effects, while there were few shared effects of climate and RSR on the LSR of herbaceous species. Our findings suggest that while geographic RSR patterns are mainly determined by winter coldness, the ecological processes driven by productivity may be critical to the filtering of regional flora into local communities. We also demonstrate that biogeographic region is not a good surrogate for regional richness, at least for our dataset. Consequently, whether biogeographic region can effectively reflect regional effects needs further examination. [ABSTRACT FROM AUTHOR]

Most of the world's terrestrial biome types can be found in China. To systematically investigate species composition and structure of China's forest communities, we launched a long-term project consisting forest vegetation surveys across China's mountains in the mid 1990s. Over the study period, we have conducted vegetation surveys for 65 mountains and collected vegetation data from about 1500 forest plots, using consistent sampling protocols. In this paper we first introduce the aims, protocols, and major research themes of the project, and then describe the major characteristics of forest communities and their geographic patterns and climatic controls. As latitude increased, diameter at breast height (DBH) and height of trees increased, while individual density of trees and woody species richness decreased. Total basal area (TBA) of trees and species richness of herbs did not vary with latitude. Contemporary climate seems to drive these patterns: temperature was the leading factor for DBH, precipitation was most important for tree height and individual density, actual evapotranspiration (a surrogate of productivity) determined woody (trees and shrubs) species richness, and rainfall was the major controller of the herb species richness. The species-abundance relationship showed that species dominance (measured by the number of individuals per species) declined significantly from boreal forests to evergreen broadleaf forests from north to south. Our results are in line with the idea that productivity drives woody species richness. Similarly, we find that biomass (measured as TBA) is invariant along the environmental gradients. However, individual density varies dramatically, in contrast to the assumptions underlying the metabolic theory of ecology. [ABSTRACT FROM AUTHOR]