Search

Adipocyte fatty acid-binding protein (A-FABP, also called FABP4, aP2) is an adipokine identified as a critical regulator of metabolic function due to its dual functions of fatty acid transport and pro-inflammation. Because of the high therapeutic potential of A-FABP inhibition for the treatment of metabolic diseases and related vascular complications, numerous inhibitors have been developed against A-FABP. However, none of these inhibitors have been approved for use in patients due to severe side effects. Here, we used a virtual screening (VS) strategy to identify potential inhibitors of A-FABP in the latest FDA-approved drug library (∼2600 compounds), aiming to explore the existing drugs with proven safety profiles. We firstly combined ligand-based machine learning and structure-based molecular docking to develop a screening pipeline for identifying A-FABP inhibitors. The screening of FDA-approved drugs identified four compounds (Cobimetinib, Larotrectinib, Pantoprazole, and Vildagliptin) with the highest scores, whose inhibitory effects on A-FABP were further assessed in cellular assays. Among the selected compounds, Cobimetinib significantly inhibited the activation of the JNK/c-Jun signaling pathway by A-FABP in mouse macrophages without causing obvious cytotoxicity. In summary, we present an integrated VS pipeline for A-FABP inhibitor screening, and identified Cobimetinib as a novel A-FABP inhibitor that may be repurposed for the treatment of metabolic diseases and associated vascular complications.

Background The therapeutic efficacy of mesenchymal stem cells (MSCs) of different tissue origins on metabolic disorders can be varied in many ways but remains poorly defined. Here we report a comprehensive comparison of human MSCs derived from umbilical cord Wharton’s jelly (UC-MSCs), dental pulp (PU-MSCs), and adipose tissue (AD-MSCs) on the treatment of glucose and lipid metabolic disorders in type II diabetic mice. Methods Fourteen-to-fifteen-week-old male C57BL/6 db/db mice were intravenously administered with human UC-MSCs, PU-MSCs, and AD-MSCs at various doses or vehicle control once every 2 weeks for 6 weeks. Metformin (MET) was given orally to animals in a separate group once a day at weeks 4 to 6 as a positive control. Body weight, blood glucose, and insulin levels were measured every week. Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were performed every 2 weeks. All the animals were sacrificed at week 6 and the blood and liver tissues were collected for biochemical and histological examinations. Results UC-MSCs showed the strongest efficacy in reducing fasting glucose levels, increasing fasting insulin levels, and improving GTT and ITT in a dose-dependent manner, whereas PU-MSCs showed an intermediate efficacy and AD-MSCs showed the least efficacy on these parameters. Moreover, UC-MSCs also reduced the serum low-density lipoprotein cholesterol (LDL-C) levels with the most prominent potency and AD-MSCs had only very weak effect on LDL-C. In contrast, AD-MSCs substantially reduced the lipid content and histological lesion of liver and accompanying biomarkers of liver injury such as serum aspartate transaminase (AST) and alanine aminotransferase (ALT) levels, whereas UC-MSCs and PU-MSCs displayed no or modest effects on these parameters, respectively. Conclusions Taken together, our results demonstrated that MSCs of different tissue origins can confer substantially different therapeutic efficacy in ameliorating glucose and lipid metabolic disorders in type II diabetes. MSCs with different therapeutic characteristics could be selected according to the purpose of the treatment in the future clinical practice.

© 2019 Elsevier B.V. Intertidal flats are shallow-water environments that undergo cyclical variations in water depth, leading to a frequent occurrence of extremely shallow water stages (ESWS; water depths 0.2 m), and the rate of change was an order of magnitude faster than during RDWS. This larger and faster bed-level change occurred even though the ESWS duration only accounted for 10% of the entire tidal cycle. This result occurred because the bed shear stress due to combined current–wave action during ESWS, was, on average, two times higher than during RDWS at the flood stage causing more extensive erosion. Whereas during the ebb stage, this shear stress during ESWS was only half of that during RDWS resulting in greater accretion. The main implications of these results are that, because ESWS occur frequently (twice every tide) and are associated with large bed shear stress and bed-level changes, these conditions are likely to play an important role in morphological changes of intertidal flats. Our study shows that ESWS have a key influence on intertidal flat hydrodynamics and sediment dynamics. Thus our results are the basis for an improved understanding of the coastal morphodynamic processes on intertidal flats.

Morphodynamics of world's river deltas are increasingly affected by human activities, which are of great ecological, economic and social implications. However, impacts of human interventions in deltaic regions are insufficientlyunderstood, especially superimposed upon diminishing sediment supplies. This study uses the heavily interfered Yangtze River delta as an example to address this issue. The morphodynamic impacts of the Deepwater Navigation Channel Project (DNCP) during 1997–2013 are investigated through process-basedmodeling approach (Delft3D) and bathymetric data analysis. The DNCP was implemented in the mouth bar area of the Yangtze River delta including the twin dikes and 19 groynes with the total length of 132.0 km. Hydrodynamic simulations indicate that the training walls resulted in weaker tidal flow and longer slack period at the East Hengsha Shoal (EHS) and stronger tidal flow at the subaqueous delta. Thus, the EHS is characterized as a sediment accumulation zone after the completion of the training walls. Subsequently, morphologicalmodeling shows enhanced accretion at the EHS and enhanced erosion at the subaqueous delta when the training walls are taken into account. Numerical experiments further demonstrate that the above changes are mainly attributed to the seaward half of the northern training walls constructed in 2002–2005. This is probably the reason for the observed accretion peak of the EHS in 2002–2007 and the gradual increase in the erosion rate of the subaqueous delta after 2002. The schematized paths of sediment transport after the DNCP indicate thatsediment eroded from the subaqueous delta serves as an important source for accretion of the mouth bar area. It is suggested that siltation promoting projects within the mouth bar area increased shallow shoal accretion and aggravated erosion at the subaqueous delta. With the overall erosion of the Yangtze River delta due to river sediment reduction, large-scale estuarine engineering projects substantially increase the complicacy of its morphodynamic pattern, which merits close attention for sustainable delta management.

Identifying the pattern of delta morphological change under decreasing sediment flux due to dam construction is essential for sustainable management in such densely populated coastal areas. In this study, we investigated the morphological processes of the Yangtze mouth bar and prodelta based on bathymetric data on a decadal-interannual scale (1958, 1978, 1997, 2002, 2007, 2010, 2013 and 2015). We found that strong accretion (205.1 Mm3 yr−1) occurred during 1958–1978, when a high sediment load (465 Mt yr−1) was supplied by the Yangtze. Afterwards, the net accumulation rate decreased to 31.9 Mm3 yr−1 in 1978–1997 and 114.6 Mm3 yr−1 in 1997–2002 as a result of riverine sediment loads decreasing to 390 Mt yr−1 and 314 Mt yr−1, respectively. Surprisingly, the net accumulation rate increased to 130.8 Mm3 yr−1 in 2002–2007, though the sediment load sharply decreased to 177 Mt yr−1. This anomaly was attributed to the construction of training walls within the mouth bar area, which induced significant accretion in groyne-sheltered areas and nearby regions. Along with a further decrease in sediment load, the entire study area converted to net erosion of −200.4 Mm3 yr−1 in 2007–2010 and −152.2 Mm3 yr−1 in 2010–2013. Stronger erosion in the former period was partly caused by intensive dredging activities in the mouth bar area. The critical sediment discharge for the Yangtze mouth bar and prodelta to retain net accretion was estimated to be ca. 218 Mt yr−1. If deducting the impacts of estuarine engineering projects on accretion/erosion during 1997–2010, the critical sediment discharge is adjusted to ca. 234 Mt yr−1. In combination with previously reported accretion-erosion conversion elsewhere in the Yangtze Delta, we inferred that most portion of the subaqueous delta has most likely converted from net accretion to net erosion in response to fluvial sediment decline, and the mouth bar area showed the latest conversion among portions of the delta. Integrated assessment and adaptive strategies are urgently required for the Yangtze Delta to survive the coming erosional stage.

Human society and ecosystems worldwide are increasinAagly threatened by water shortages. Despite numerous studies of climatic impacts on water availability, little is known about the influences of socioeconomic development on streamflow and water sustainability. Here, we show that the streamflow from the Yellow River to the sea has decreased by more than 80% in total over the last 60 years due to increased water consumption by agricultural, industrial and urban developments (76% of the streamflow decrease, similarly hereinafter), decreased precipitation (13%), reservoir construction (6%) and revegetation (5%). We predict that if the past trends in streamflow will continue, year-round dry-up in the lower Yellow River will commence in the late 2020s or early 2030s, unless effective countermeasures such as water diversion from the Yangtze River are taken. These results suggest that streamflow in semiarid basins is highly vulnerable to human impacts and that streamflow decline would in turn hinder further socioeconomic development and endanger river-sea ecosystems.

Accelerating sea-level rise and decreasing riverine sediment supply are widely considered to lead to global losses of deltaic marshes and their valuable ecosystem services. However, little is known about the degree to which the related erosion of the seaward delta front can provide sediments to sustain salt marshes. Here, we present data from the mesomacrotidal Yangtze Delta demonstrating that marshes have continued to accrete vertically and laterally, despite rapid relative sea-level rise (similar to 10 mm yr(-1)) and a > 70% decrease in the Yangtze River sediment supply. Marsh progradation has decelerated at a lower rate than fluvial sediment reduction, suggesting an additional source of sediment. We find that under favorable conditions (e.g., a mesomacrotidal range, strong tidal flow, flood dominance, sedimentary settling lag/scour lag effects, and increasing high-tide level), delta-front erosion can actually supply sediment to marshes, thereby maintaining marsh accretion rates in balance with relative sea-level rise. Comparison of global deltas illustrates that the ability of sediment remobilization to sustain marshes depends on coastal processes and varies by more than an order of magnitude among the world's major deltas.

The activity of benthic organisms can strongly influence sediment dynamics in an intertidal flat. However, few studies have conducted a quantitative assessments of the effect of benthic organisms on erosion-accretion processes under field conditions. The aim of this study was to quantify the effects of the benthic clam Meretrix meretrix Linnaeus (M. meretrix) on bed erodibility and sediment erosion-accretion processes in an intertidal flat. Within the cultivation zone at site A, M. meretrix is present in large numbers (up to 137 individuals per square meter). On the other hand, site B is located outside the cultivation zone. At this site, which is only 500 m away from site A alongshore, M. meretrix forms a sparse population with only 3.7 individuals per square meter. The results showed that the critical shear stress for erosion, denoted by τce, was 0.22 and 0.32 N/m2 at sites A and B, respectively, and the magnitudes of bed-level change were significantly higher at site A than site B. These results reveal the large effect of M. meretrix on decreasing τce, augmenting the erosion rate when the bed shear stress due to combined currents and waves, denoted by τcw, was higher than τce, and conversely enhancing the accretion rate when τcw < τce. The changes induced in these parameters are likely to have a large impact on model predictions of bed erodibility, sedimentary processes, and morphological evolution. Thus, integrated field measurements of hydrodynamic and bed-level changes, accompanied by simultaneous biological sampling, may help to improve the parameterization of hydro-sedimentary and morphodynamic models for shallow-water environments. Fil: Shi, Benwei. East China Normal University; China. Tongji University; China Fil: Pratolongo, Paula Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina Fil: Du, Yongfen. Nanjing Normal University; China Fil: Li, Jiasheng. Nanjing University; China Fil: Yang, S. L.. East China Normal University; China Fil: Wu, Jihua. Fudan University; China Fil: Xu, Kehui. State University of Louisiana; Estados Unidos Fil: Wang, Ya Ping. East China Normal University; China

Changes in riverine suspended and riverbed sediments have environmental, ecological and social implications. Here, we provide a holistic review of water and sediment transport and examine the human impacts on the flux, concentration and size of sediment in the Yangtze River in recent decades. We find that most of the fluvial sediment has been trapped in reservoirs, except for the finest portion. Furthermore, soil-conservation since the 1990s has reduced sediment yield. From 1956-1968 (pre-dam period) to 2013–2015 (post-dams and soil-conservation), the sediment discharge from the sub-basins decreased by 91%; in the main river, the sediment flux decreased by 99% at Xiangjiaba (upper reach), 97% at Yichang (transition between upper and middle reaches), 83% at Hankou (middle reach), and 77% at Datong (tidal limit). Because the water discharge was minimally impacted, the suspended sediment concentration decreased to the same extent as the sediment flux. Active erosion of the riverbed and coarsening of surficial sediments were observed in the middle and lower reaches. Fining of suspended sediments was identified along the river, which was counteracted by downstream erosion. Along the 700-km-long Three Gorges Reservoir, which retained 80% of the sediment from upstream, the riverbed gravel or rock was buried by mud because of sedimentation after impoundment. Along with these temporal variations, the striking spatial patterns of riverine suspended and riverbed sediments that were previously exhibited in this large basin were destroyed or reversed. Therefore, we conclude that the human impacts on sediment in the Yangtze River are strong and systematic.

After more than 50,000 dams were built in the Yangtze basin, especially the Three Gorges Dam (TGD) in 2003, the sediment discharge to the East China Sea decreased from 470 Mt/yr before dams to the current level of ~140 Mt/yr. The delta sediment's response to this decline has interested many researchers. Based on a dataset of repeated samplings at 44 stations in this study, we compared the surficial sediment grain sizes in the southern Yangtze subaqueous delta front for two periods: pre-TGD (1982) and post-TGD (2012). External factors of the Yangtze River, including water discharge, sediment discharge and suspended sediment grain size, were analysed, as well as wind speed, tidal range and wave height of the coastal ocean. We found that the average median size of the sediments in the delta front coarsened from 8.0 µm in 1982 to 15.4 µm in 2012. This coarsening was accompanied by a decrease of clay components, better sorting and more positive skewness. Moreover, the delta morphology in the study area changed from an overall accretion of 1.0 cm/yr to an erosion of − 0.6 cm/yr. At the same time, the riverine sediment discharge decreased by 70%, and the riverine suspended sediment grain size increased from 8.4 µm to 10.5 µm. The annual wind speed and wave height slightly increased by 2% and 3%, respectively, and the tidal range showed no change trend. Considering the increased wind speed and wave height, there was no evidence that the capability of the China Coastal Current to transport sediment southward has declined in recent years. The sediment coarsening in the Yangtze delta front was thus mainly attributed to the delta's transition from accumulation to erosion which was originally generated by river damming. These findings have important implications for sediment change in many large deltaic systems due to worldwide human impacts.

Understanding erosion and accretion dynamics during an entire tidal cycle is important for assessing their impacts on the habitats of biological communities and the long-term morphological evolution of intertidal mudflats. However, previous studies often omitted erosion and accretion during very shallow-water stages (VSWS, water depths 0.2 m (i.e., probe submerged) are considered. These findings suggest that the magnitude of bed-level changes during VSWS should not be neglected when modeling morphodynamic processes. Our results are useful in understanding the mechanisms of micro-topography formation and destruction that often occur at VSWS, and also improve our understanding and modeling ability of coastal morphological changes.

The environmental impact of the Three Gorges Dam has been a subject of vigorous academic, political and social debate since its inception. This includes the key issue of post-dam river channel erosion, which was predicted by the feasibility study to extend to the river mouth. In this paper we examine the geomorphic response of the channel of the middle Yangtze for 660 km downstream of the dam. Using data on channel characteristics, bed material and sediment transport, we show that in the decade following the dam closure, pre-dam seasonal erosion has been replaced by year-round erosion, a pattern most marked at the upstream end of the study area. The sediment carrying capacity of the river channel has been largely reduced below the dam. The locus of bed scour has moved progressively downstream, ceasing as the bed material became too coarse to be transported (e.g. D50: 0.29 mm pre-dam coarsened to 20 mm below the dam by 2008). About 400 km below the dam there is a reduction in channel slope that changes the sediment carrying capacity from 0.25 kg m−3 to only about 0.05 kg m−3, which is insufficient to move bed sediment. The new long-term hydro-morphological equilibrium that will be established in this section of the middle Yangtze will prevent the further incision downstream initiated by the Three Gorges Dam. The results suggest that the full extent of adverse environmental impact predicted by the pre-dam studies will not eventuate.

The variation in suspended sediment concentration (SSC) has an important impact on the protection of estuarine shoal wetlands and the maintenance of waterways. Typhoons (tropical cyclones), one of the most severe meteorological disasters, frequently occur along the southeastern coasts of China and substantially affect the spatial-temporal distribution of SSC in the Yangtze Estuary. In this study, the spatial-temporal distribution of SSC was observed at high frequency through hourly geostationary satellite remote sensing during four typhoon events, namely, Typhoons Damrey/Saola (August 2012), Soulik (July 2013), Matmo (July 2014) and Dujuan (September 2015). Such observation is difficult to achieve through in situ approaches due to the unsafe working conditions created by typhoon winds. Moreover, wind speed, wave height and period, and bottom shear stress (BSS) data combined with turbidity data were used to analyze the causes of typhoon-induced SSC variations. The results indicated that the average wind-driven significant wave height during typhoons was 2.1-fold higher than that in pre-typhoon periods. In the lower mouth of the Yangtze Estuary and in Hangzhou Bay, the SSC increased by 0.14–0.33 g/L, whereas in the upper mouth, the SSC was less affected by wind. The significant increase in SSC persisted for 1–2 days following typhoon transit. With the assistance of the FVCOM model, it was observed that the enhanced wave-current dynamics and increased BSS during the typhoons were the main reasons for the sharp increase in SSC. Moreover, it was inferred from the satellite images that sediment exchange occurs between channels and shoals during a typhoon, which affects the SSC distribution for up to one month.

The Yangtze River has experienced a sharp sediment decrease as a result of extensive dam constructions since the 1980s, similar to the sediment decline in the Mississippi River since the 1950s. Historical land losses in the Mississippi Delta have been reported extensively, but this issue in the Yangtze Delta is still under debate. Here we presented the morphological responses of deltaic wetlands to the sediment decline with the comparison of hydrodynamic forces in the Yangtze and Mississippi deltas. We found that the wetlands of the Yangtze Delta continued their expansion even after the sediment decline since 2003 when the Three Gorges Dam began operation, in contrast to the historical scenario in the Mississippi. Based on observations at water depth around 10 m in both of the open subaqueous deltas, the bed shear stresses caused by waves and currents (τcw) during neap and spring tides were 0.18–0.30 N/m2 in the Yangtze Delta and 0.09–0.10 N/m2 in the Mississippi Delta under fair weather conditions. The periods of τcw > τcr (the critical bed shear stress for erosion) occupied on average 80% of a tidal cycle in the Yangtze Delta but only 47% of a cycle in the Mississippi Delta. The rates of relative sea-level rise and riverine sediment decrease in these two deltas are similar, but the sediment-supply capacity to the deltaic wetlands from the Yangtze's subaqueous delta is much larger than that of the Mississippi Delta. Thus, we infer that in contrast to the historical land loss after sediment decline in the Mississippi Delta, the Yangtze deltaic wetlands stand still with a good opportunity to survive for years to decades with the aid of abundant sediment from the subaqueous delta due to higher capacity of seabed erodibility by stronger coastal hydrodynamics.

Deltas are widely threatened by sediment starvation and climate change. Erosion potential is an important indicator of delta vulnerability. Here, we investigate the erosion potential of the Yangtze Delta. We found that over the past half century the Yangtze’s sediment discharge has decreased by 80% due to the construction of >50,000 dams and soil conservation, whereas the wind speed and wave height in the delta region have increased by 5–7%, and the sea level has risen at a rate of 3 mm/yr. According to hydrodynamic measurements and analyses of seabed sediments, the period when bed shear stress due to combined current-wave action under normal weather conditions exceeds the critical bed shear stress for erosion (τ cr ) accounts for 63% of the total observed period on average and can reach 100% during peak storms. This explains why net erosion has occurred in some areas of the subaqueous delta. We also found that the increase with depth of τ cr is very gradual in the uppermost several metres of the depositional sequence. We therefore expect that the Yangtze subaqueous delta will experience continuous erosion under sediment starvation and climate change in the next decades of this century or even a few centuries.

Hydrodynamics and sediment dynamics vary greatly in tide-dominated estuaries worldwide, but there is a paucity of data of large tide-dominated estuary systems due to difficulties of observation in a large spatial scale. In this study, we investigate sediment dynamic transitions in a 660-km long section between the tidal limit and mouth of the Yangtze River. We found that tidal effects are almost undetectable in the uppermost 100-km section, but the mean tidal range gradually increases downstream to nearly 3 m at the river mouth. Flow is generally unidirectional in the uppermost 400-km section, although its velocity changes in response to flood/ebb tidal dynamics; in the lowest 250-km section, flow is bidirectional, and ebb flow durations decrease towards the sea. In the lowermost 100 km, the ebb flow durations decreases to below 60%, and the flow is dominated by tidal currents. Salinity is only detectable in the lowest 100-km section due to the dominance of Yangtze River water discharge. Bed sediments mainly include sand in the uppermost 500-km section, whereas mud dominates in the remaining areas. In contrast, the median grain size of the suspended sediments was found to be greater in the lowest 100-km section (8–13 μm) than in the upper sections (5–6 μm) due to strong exchanges between suspended and near bed sediments. The suspended sediment concentration (SSC) was found to be low ( 1 g/L and both surface-bottom and intratidal variabilities occurred. The rates of sediment parameter changes were rapid in the river-sea transitional zone, and this zone may shift upstream and downstream in response to the relative contributions of the river, tides and waves. A conceptual model of the river-sea transition of sediment dynamics for the Yangtze estuary was established, and this model shed light on quantitative studies of sediment dynamics in other large tide-impacted estuaries worldwide.

As the effects of global warming on climate have a wide spatial variability, regional studies of temporal climate trends are critical. This study investigates the effect of global warming on temperature and precipitation trends in the Yellow, Yangtze and Pearl River basins (the Three Basins) of China over the past 58 years (1956–2013). Over this time period, the mean warming rate in the Three Basins (0.22 °C/10 yr) was close to that for the global land surface (0.21 °C/10 yr). However, the warming rate showed high spatial variability across the study region, ranging from 0.05 °C/10 yr to 0.49 °C/10 yr. These rates tend to increase with latitude and elevation and toward very large cities (e.g., Shanghai). The warming rate in the Three Basins varied by season, it was lower in summer (0.14 °C/10 yr) and higher in winter (0.29 °C/10 yr). In spite of the warming trend, no statistically significant increase or decrease in precipitation was found for the Three Basins over the past 58 years.

Coastal currents that originate from large rivers play a key role in delivering sediment to shelf regions. Quantifying their transport capability is therefore essential to understanding the sediment budgets and the consequent deposition or erosion of coastal areas. In February 2012, we observed the sediment transport carried by the Min-Zhe Coastal Current that originates from the Yangtze River mouth and calculated a flux of 18.7 tons per second on a cross-shore section. In this period the coastal current was at a typical status, which allowed us to estimate a total annual sediment transport of 0.27billion tons southward. This result was more than three times the present annual Yangtze River sediment discharge, suggesting that considerable net sediment removal occurs in the coastal regions. The sediment transport 0.27 billion tons/year is probably the deposition/erosion threshold for the East China Sea coast north of our study site. Analysis of historical Yangtze River sediment influx records showed, that the onset and acceleration of coastal erosion was closely linked with the operation of the Three Gorges Dam (TGD) upstream of the Yangtze River.

Wind is an important regulator of coastal erosion and accretion processes that have significant ecological and engineering implications. Nevertheless, previous studies have mainly focused on storm−generated changes in the bed level. This paper aims to improve the understanding of wind−induced erosion–accretion cycles on intertidal flats under normal (non−stormy) weather conditions using data that relates to the wave climate, near−bed 3D flow velocity, suspended sediment concentration, and bed−level changes on a mudflat at the Yangtze Delta front. The following parameters were calculated at 10−minute intervals over 10 days: the wind wave orbital velocity (Uδ), bed shear stress from combined current–wave action, erosion flux, deposition flux, and predicted bed−level change. The time series of measured and predicted bed−level changes both show tidal cycles and a 10−day cycle. We attribute the tidal cycles of bed−level changes to tidal dynamics, but we attribute the 10−day cycle of bed−level changes to the interaction between wind speed/direction and neap−spring cyclicity. We conclude that winds can significantly affect bed−level changes in mudflats even during non−stormy weather and under macro−mesotidal conditions and that the bed−level changes can be predicted well using current–wave–sediment combined models. This article is protected by copyright. All rights reserved.

Accurate estimations for the bed shear stress are essential to predict the erosion and deposition processes in estuaries and coasts. This study used high-frequency in situ measurements of water depths and near-bed velocities to estimate bed shear stress on an open intertidal flat in the Yangtze Delta, China. To determine the current-induced bed shear stress (τc) the in situ near-bed velocities were first decomposed from the turbulent velocity into separate wave orbital velocities using two approaches: a moving average (MA) and energy spectrum analysis (ESA). τc was then calculated and evaluated using the log-profile (LP), turbulent kinetic energy (TKE), modified TKE (TKEw), Reynolds stress (RS), and inertial dissipation (ID) methods. Wave-induced bed shear stress (τw) was estimated using classic linear wave theory. The total bed shear stress (τcw) was determined based on the Grant–Madsen wave–current interaction model (WCI). The results demonstrate that when the ratio of significant wave height to water depth (Hs/h) is greater than 0.25, τcw is significantly overestimated because the vertical velocity fluctuations are contaminated by the surface waves generated by high winds. In addition, wind enhances the total bed shear stress as a result of the increases in both τw and τc generated by the greater wave height and reinforcing of vertical turbulence, respectively. From a comparison of these various methods, the TKEw method associated with ESA decomposition was found to be the best approach because: (1) this method generates the highest mean index of agreement; (2) it uses vertical velocities that are less affected by Doppler noise; and (3) it is less sensitive to the near-bed stratification structure and uncertainty in bed location and roughness.

Ocean salinity is often used as a dynamical tracer for investigating the Kuroshio intrusion into the South China Sea (SCS). In this study, we found that the upper-ocean water in the SCS had a freshening trend since the early 1990s. Salinity in the upper 100 m of the SCS ( S SCS ) decreased by ~0.24 psu in the period 1993–2012, yielding a negative trend of −0.012 psu yr −1 . The maximum freshening occurred in the surface layer west of the Luzon Strait, and freshening gradually lessened from northeast to southwest and with depth, indicating the important influence of the Kuroshio intrusion. Quantitative analysis of salinity budget from the surface to 100 m depth in the SCS suggests that the weakened Kuroshio intrusion is the leading factor controlling the S SCS freshening, while the increased air-sea freshwater flux plays a minor role. Based on GODAS (Global Ocean Data Assimilation System) model output, the Luzon Strait transport (LST) in the upper 100 m decreased in a negative trend of −0.12 Sv yr −1 (1 Sv=10 6 m 3 s −1 ) from 1993 to 2012, corresponding to a freshening trend of the S SCS at a rate of −0.011 psu yr −1 . Both the LST and S SCS changes are closely related to the Pacific Decadal Oscillation (PDO). Our findings demonstrate that the strength of the Kuroshio intrusion into the SCS weakened markedly since the PDO phase shifted in 1990s, which resulted in the pronounced freshening of the SCS water.

This paper reviews the morphological change in the Yangtze River delta due to increasing human impacts from three major aspects. The first is the reduction of sediment supply to the ocean due to dam construction, soil conservation, and sand mining within the Yangtze River basin. The reduced sediment supply has decreased the progradation rate of the delta and triggered erosion in the front of the delta. The second impact relates to the reclamation of intertidal wetlands by human activities. Since the 1950s, approximately 1100 km 2 of intertidal land has been embanked, resulting in the disappearance of salt marshes and even the entire intertidal zone along some sections of the coastline. The third change in the delta due to human interference is the construction of deep-waterway structures at the mouth bar, which has greatly modified the local hydrodynamics and morphology. Sediment accretion has increased significantly in these areas as a result of sheltering by these deep-waterway structures. This review shows that human activities have severely altered the natural balance among the hydrodynamics and sediment supply, affecting the morphological features of the Yangtze River watershed and delta. Human impacts on the morphological evolution of deltaic coasts in general are becoming an increasingly concern, and more attention should be paid to the management and mitigation of these effects.

Ischemic stroke is a cerebrovascular disease with high morbidity, high mortality, and high disability, representing a serious threat to human life and health. Clinically, the extensive injury caused by ischemic stroke results from ischemia-reperfusion (I/R) injury thrombolytic treatment. However, there are few reports on the use of medications in the subacute stage of cerebral I/R. Baicalein (5,6,7-trihydroxyflavone) is a biologically active ingredient extracted from the root of Scutellaria baicalensis Georgi. In the present study, we investigated the therapeutic effect of baicalein administered in the subacute phase of cerebral I/R injury in a rat model of ischemia induced by occlusion of the middle cerebral artery (MCA). Rats were treated daily with baicalein (200 mg/kg, i.g.) in the subacute phase (24 h after reperfusion) for 7 days. The results showed that baicalein significantly reduced neurobehavioral deficits and decreased brain infarct volume from 18.99% to 7.41%. Immunofluorescence analysis of the ischemic penumbra showed that baicalein significantly reduced expression of the M1 marker, cluster of differentiation (CD) 16 and CD86, and increased expression of the M2 marker, CD 163 and CD206, indicating that baicalein inhibited M1 transformation and promoted M2 transformation of microglia/macrophage to inhibit neuroinflammation. Moreover, baicalein suppressed NF-κB signaling by reducing IκBα phosphorylation and nuclear translocation of NF-κB/p65, which decreased the release of the pro-inflammatory factors IL-6, IL-18, and TNF-α. In addition, baicalein reduced phosphorylation of JNK, ERK and p38, which are involved modulation of microglia/macrophage M1/M2 polarization. Western blot analysis of apoptosis- and autophagy-related proteins showed that baicalein increased the Bcl-2/Bax ratio and reduced caspase-3 expression to decrease neuronal apoptosis and ameliorate neuronal loss. Baicalein also decreased the LC3-II/LC3-I ratio and promoted phosphorylation of the PI3K/Akt/mTOR signaling pathway which implied inhibition of autophagy. These observations suggest that baicalein exerts neuroprotective effects by reducing neuroinflammation, apoptosis and autophagy, and protects against cerebral I/R injury in the subacute phase in vivo.

The prediction of the erosion of mudflats is hampered by inaccurate estimates of the erodibility distribution of the sediment bed. To investigate how erodibility varies in space and what the vertical distribution over the sediment depth is, comprehensive observations of the sediment properties, hydrodynamics and bed-level changes were conducted on an intertidal flat in the Western Scheldt Estuary, the Netherlands. The erosion potential on a mudflat is determined by the critical shear stress for erosion (τe), erosion rate coefficient (M) and local hydrodynamic conditions. A clear difference in hydrodynamic forcing was observed, leading to significant bed level variations at the low water line, where erosion often occurs during very shallow water condition, and a nearly constant bed level at the upper part. The erosion parameters τe and M could be determined over a sediment bed of 12 cm at the low water line. The erosion coefficient M can be considered constant with depth, although there is a large spreading. A clear vertical variation of τe was found: τe increased significantly downward from 0.10 Pa at the sediment surface to 1.13 Pa at 12 cm below the surface. Additionally, there was a strong indication that the presence of diatoms enhanced τe in the upper 2 mm of sediment by five times of the abiotic τe (from 0.09 Pa to 0.46 Pa). These findings lead to the following improvement for predicting morphological changes of tidal mudflats: (1) very shallow conditions should be better simulated, (2) the vertical distribution of τe should be considered. Otherwise, erosion rates can be overestimated, especially during extreme events, because exposure of the deeper well-consolidated layer likely occurs; and (3) an appropriate description of the effect of diatoms should be considered as part of the bottom boundary condition.

Xiaoxuming decoction (XXMD), a classic traditional Chinese medicine (TCM) prescription, has been used as a therapeutic in the treatment of stroke in clinical practice for over 1200 years. However, the pharmacological mechanisms of XXMD have not yet been elucidated. The purpose of this study was to develop neuroprotective models for identifying neuroprotective compounds in XXMD against hypoxia-induced and H2O2-induced brain cell damage. In this study, a phenotype-based classification method was designed by machine learning to identify neuroprotective compounds and to clarify the compatibility of XXMD components. Four different single classifiers (AB, kNN, CT, and RF) and molecular fingerprint descriptors were used to construct stacked naïve Bayesian models. Among them, the RF algorithm had a better performance with an average MCC value of 0.725±0.014 and 0.774±0.042 from 5-fold cross-validation and test set, respectively. The probability values calculated by four models were then integrated into a stacked Bayesian model. In total, two optimal models, s-NB-1-LPFP6 and s-NB-2-LPFP6, were obtained. The two validated optimal models revealed Matthews correlation coefficients (MCC) of 0.968 and 0.993 for 5-fold cross-validation and of 0.874 and 0.959 for the test set, respectively. Furthermore, the two models were used for virtual screening experiments to identify neuroprotective compounds in XXMD. Ten representative compounds with potential therapeutic effects against the two phenotypes were selected for further cell-based assays. Among the selected compounds, two compounds significantly inhibited H2O2-induced and Na2S2O4-induced neurotoxicity simultaneously. Together, our findings suggested that machine learning algorithms such as combination Bayesian models were feasible to predict neuroprotective compounds and to preliminarily demonstrate the pharmacological mechanisms of TCM.

The Yangtze Estuary in China has been intensively influenced by human activities including altered river and sediment discharges in its catchment and local engineering projects in the estuary over the past half century. River sediment discharge has significantly decreased since the 1980s because of upstream dam construction and water-soil conservation. We analyzed bathymetric data from the Yangtze Estuary between 1958 and 2010 and divided the entire estuary into two sections: inner estuary and mouth bar area. The deposition and erosion pattern exhibited strong temporal and spatial variations. The inner estuary and mouth bar area underwent different changes. The inner estuary was altered from sedimentation to erosion primarily at an intermediate depth (5–15 m) along with river sediment decline. In contrast, the mouth bar area showed continued accretion throughout the study period. The frequent river floods during the 1990s and simultaneously decreasing river sediment probably induced the peak erosion of the inner estuary in 1986–1997. We conclude that both sediment discharge and river flood events played important roles in the decadal morphological evolution of the Yangtze Estuary. Regarding the dredged sediment, the highest net accretion rate occurred in the North Passage where jetties and groins were constructed to regulate the navigation channel in 1997–2010. In this period, the jetties induced enhanced deposition at the East Hengsha Mudflat and the high accretion rate within the mouth bar area was maintained. The impacts of estuarine engineering projects on morphological change extended beyond their sites.

This paper is concerned with delta evolution in response to human activities in the Pearl River estuary. Utilizing more than 50 years data bathymetric data, together with simulation fluvial discharge data, the net accretion rate in the Lingdingyang subaqueous delta decreased from 16.6 mm/y over the period 1955–1964 to 1.6 mm/y for the period 1998–2008 because there was a dramatic downward trend in the sediment load. In particular, the closure of the Longtan Dam (LTD) in 2006 resulted in the sediment load entering the Pearl River falling from 75 Mt/y (annual average: 1954–2006) to 25.2 Mt/y, a decrease of ∼67%. Another reason may be sand mining in the Lingdingyang estuary. Based on the linear relationship between sediment load and accumulation rate, an annual average sediment load of 21.7 Mt/y carried into the Lingdingyang estuary is the critical threshold value that separates delta progradation from recession. However, the outer subaqueous delta in the Modaomen estuary underwent deposition in the same period, because there is no obvious change in sediment load into the area during 1954–2008. In the coming decades, ongoing human interferences will reduce the fluvial sediment load entering the sea, which probably will result in a phase of general delta recession replacing delta progradation.

Many estuaries worldwide are modified, primarily driven by economic gain or safety. These works, combined with global climate changes heavily influence the morphologic development of estuaries. In this paper, we analyze the impact of human activities on the morphodynamic developments of the Scheldt Estuary and the Wadden Sea basins in the Netherlands and the Yangtze Estuary in China at various spatial scales, and identify mechanisms responsible for their change. Human activities in these systems include engineering works and dredging activities for improving and maintaining the navigation channels, engineering works for flood protection, and shoreline management activities such as land reclamations. The Yangtze Estuary is influenced by human activities in the upstream river basin as well, especially through the construction of many dams. The tidal basins in the Netherlands are also influenced by human activities along the adjacent coasts. Furthermore, all these systems are influenced by global changes through (accelerated) sea-level rise and changing weather patterns. We show that the cumulative impacts of these human activities and global changes may lead to exceeding thresholds beyond which the morphology of the tidal basins significantly changes, and loses its natural characteristics. A threshold is called tipping point when the changes are even irreversible. Knowledge on such thresholds or tipping points is important for the sustainable management of these systems. We have identified and quantified various examples of such thresholds and/or tipping points for the morphodynamic developments at various spatial and temporal scales. At the largest scale (mega-scale) we consider the sediment budget of a tidal basin as a whole. A smaller scale (macro-scale) is the development of channel structures in an estuary, especially the development of two competing channels. At the smallest scale (meso-scale) we analyze the developments of tidal flats and the connecting channels.

An understanding of erosional and depositional processes in intertidal wetland environments is of great importance to coastal geomorphologists, ecologists, and engineers. To evaluate the morphodynamic response of intertidal mudflats and saltmarshes to tidal inundation, we measured water depth, wave activity, current velocity profiles, suspended sediment concentration (SSC), and sediment composition at a dynamic mudflat–saltmarsh transition on eastern Chongming Island, at the Yangtze delta front, China. Based on these data, we calculated bed shear stresses generated by the combined current–wave action ( τ cw ), and the critical shear stress required to erode the surface sediments ( τ ce ), and so were able to calculate the erosional ( E ) and depositional ( D ) fluxes. The erodibility parameter ( M E ) and settling velocity ( w s ) used in the calculations of E and D were calibrated using daily measurements of bed-level change. Our results showed that the mudflat experienced alternating phases of net erosion and net deposition during tidal inundation. The burst-based changes in bed level ranged from −0.92 (net erosion) to +0.43 mm/10 min, and the cumulative bed-level changes over an entire tidal cycle ranged from approximately 0 to −5.4 mm (net erosion), with an average change of −3.4 mm/tide (net erosion) over five consecutive spring tides. In contrast, only net deposition was recorded on the saltmarsh during our observations. The burst-based changes in bed level ranged from around 0 to +0.56 mm/10 min, and the cumulative changes over a tidal cycle ranged from around 0 to +5 mm, with an average of +2.6 mm/tide for the five consecutive spring tides. We conclude that net erosion and net deposition during tidal cycles alternate on the mudflat, but that only net deposition occurs on the saltmarsh.

The vertical distribution of suspended sediment in continental shelf waters has significant implications for water quality, aquatic ecology, and sediment transport. Nevertheless, there have been relatively few systematic field studies aimed at determining whether a general vertical trend in suspended sediment concentration (SSC) exists, or how any such vertical trend can be expressed mathematically. In this study, based on 402 individual SSC profiles measured hourly during 16 dual-tide voyages at 8 stations in the outer Yangtze Estuary, we found that SSC followed an average depth profile that was smoothly concave-up. This average profile, and the relationship between SSC and height above the seabed, was exponential (R2>0.99). In comparison, the traditional Rouse equation based on hydrodynamics describes the measured average SSC profile poorly, in that the greater the distance from the near-bed height (where the reference SSC is taken), the greater the deviation of the simulated SSC from the measured SSC. However, in this study, a new approach was developed to overcome this flaw in the Rouse equation, which divides the equation into two parts. One part uses a reference SSC from a near-bed level, and an upwards decreasing coefficient, in the same way as the conventional Rouse equation. Conversely, the other part uses a reference SSC from at the water surface, and a downwards decreasing coefficient. Our modified hydrodynamics-based equation expresses the measured SSC well, with an R2 between the simulated and measured SSCs exceeding 0.99. According to the average SSC profiles, the near-bed SSC was 2.8 times greater than the SSC at the water surface (close to the value of 3 suggested for modeling studies in the absence of empirical data), and the depth-averaged SSC was 1.8 times greater than the SSC at the water surface. We also found that the average SSC profile showed a uniform (from water surface to seabed) decline in SSC (25%) in response to the dramatic decline in the suspended sediment load supplied by the Yangtze River over the past three decades. However, the shape and vertical ratio of the average SSC profile have changed little, which suggests that the general form of the SSC profile is determined mainly by local hydrodynamics and sediment properties, and not by fluvial sediment supply.

Although large dams have been constructed and continue to be constructed on many rivers, the lack of long-term gauging data often makes it difficult to document either reservoir sedimentation or the dams' downstream impacts. More than 50 years of water and sediment data from 20 gauging stations within the Yangtze River's basin provide us a unique opportunity to delineate the impacts from the Three Gorges Dam (TGD), the world's largest dam. During the first decade after TGD completion in 2003, 1.8 Gt of sediments were trapped in the Three Gorges Reservoir (TGR). The TGR's sediment retention rate increased from ~ 65% during the first three years of operation to ~ 85% by 2008–2012, when the TGD was in normal operation; in the low-discharge drought years of 2006 and 2011, reservoir retention exceeded 90%. Sedimentation in the TGR has been discontinuous, the most prominent depocenters being at the broad section near the up-river entrance to the reservoir and just upstream of the dam, where sediment thickness locally exceeds 60 m. Median size of the sediments trapped in the TGR is 11 μm, whereas sediments discharged from the TGR are finer than 5 μm. As a result of sediment retention in the TGR, the river downstream has been eroded at a rate of 65 Mt/yr. Riverbed sediments have coarsened considerably in the first several hundred kilometers downstream of TGD. Sediment discharge into the Yangtze estuary, as measured at the Datong downstream gauging station, decreased by 130 Mt/yr relative to the normal water years of 2001–2002, nearly 90% of which can be attributed to the TGD. With planned construction of large upstream Cascade Reservoirs, the amount of sediment entering the TGR will decline dramatically, thus reducing sedimentation in the TGR and thereby extending its lifespan; by the end of the 21st century, the TGR should have retained more than 80% of its original storage capacity. Sediment outflow from the TGR will likely be less than 15 Mt/yr, compared to 50 Mt/yr at present. Even with downstream channel erosion, the long-term average sediment discharge into the Yangtze estuary in future decades most likely will decrease to ca. 110 Mt/yr, only 20% of its level in the 1960s, and further delta erosion is expected.

Many deltas are likely undergoing net erosion because of rapid decreases in riverine sediment supply and rising global sea levels. However, detecting erosion in subaqueous deltas is usually difficult because of the lack of bathymetric data. In this study, by comparing bathymetric data between 1981 and 2012 and surficial sediment grain sizes from the Yangtze subaqueous delta front over the last three decades, we found severe erosion and significant sediment coarsening in recent years since the construction of Three Gorges Dam (TGD), the largest dam in the world. We attributed these morphological and sedimentary variations mainly to the human-induced drastic decline of river sediment discharge. Combined with previous studies based on bathymetric data from different areas of the same delta, we theorize that the Yangtze subaqueous delta is experiencing overall (net) erosion, although local accumulation was also noted. We expect that the Yangtze sediment discharge will further decrease in the near future because of construction of new dams and delta recession will continue to occur.

Short-term bed-level variability in tidal wetlands has important implication both for ecology and engineering. In this study, we combined in situ measurements with model simulations to quantify short-term bed-level changes on a meso-macrotidal wetland in the Yangtze River Delta. On the middle flat, we observed erosion during neap-to-mean tides under onshore moderate-to-strong winds, and bed recovery during subsequent spring tides, when winds were both offshore and weaker, suggesting that winds can overturn the neap–spring cyclicity of bed-level changes even on meso–macrotidal mudflats. The magnitude of bed-level changes was smaller on both sides of the middle flat, while the smallest changes occurred on the salt marsh. Observed bed-level changes were reconstructed using a single-point bed-level change model, which incorporates in situ measured parameters of hydrodynamics (waves and currents), suspended sediment concentrations, and bed sediment properties. We conclude that the relative importance of waves and tides in intertidal wetland erosion and accretion can vary temporally (due to changes in balance between wave and tidal energies) and spatially (because of changes in elevation and vegetation in the cross-shore profile). Our study also reflects the advantage of combination of in situ measurement with simulation in detecting short-term variability of tidal flats.

Numerous deltaic coasts in the world are eroding in response to a decline in sediment supply as a consequence of river damming. Near-bed sediment dynamics are key mechanisms of erosion and deposition. To understand the sediment dynamics of an exposed, erosional mudflat on the delta front of the Yangtze River, China, we measured wave parameters, near-bed current profiles (for 30 layers located up to 50 cm above the seabed), suspended sediment concentration (SSC) profiles (at 6, 15, 35, and 75 cm above the seabed), bed-level changes, and sediment properties, at a low flat site. We found that bed shear stresses induced by waves can be important to sediment dynamics on the mudflat, even in periods of offshore winds. SSC-measurements close to the seabed revealed the presence of a highly dynamic fluid mud layer. At the high tides, SSC at the near-bed 6-cm layer increased to > 8 kg/m3, as a result of sediment deposition from the overlying water column. During the ebb tides, however, an increase in hydrodynamic variations resulted in resuspension, and the near-bed SSC was reduced to

The sediment load of the Yangtze River (China) is decreasing because of construction of dams, of which the Three Gorges Dam (TGD) is the best known example. The rate of the decline in sediment load is well known, but changes in the sediment grain size distribution have not been given much attention. The TGD mostly traps sand and silt while clay is flushed through the reservoir. A large amount of sand is available in the Yangtze River downstream of the reservoir, and therefore the pre-dam sand concentration is not substantially reduced. The availability of silt on the Yangtze River bed is limited, and it is expected that most silt will be removed from the riverbed within one to two decades. In order to evaluate the impact of the change in grain size distribution on the tidal flats of the Yangtze Estuary, a highly schematized tidal flat model is setup. This model broadly reveals that the observed deposition rates are exceptionally large because of the high sediment concentration, the abundance of silt, the seasonal dominance of waves (shaping a concave profile), and the offshore tidal asymmetry. The model further suggests that deposition rates will be limitedly influenced by reductions in clay or fine silt but strongly impacted by reductions in median to coarse silt. The response of the downstream morphology to reservoir sedimentation therefore strongly depends on the type of trapped sediment. As a consequence, silt-dominated rivers, such as the Yangtze River and the Yellow River may be more strongly impacted than sand-dominated systems.

The grain size of river sediments changes systematically downstream from source to sink, and is influenced by catchment lithology, geomorphology, hydrology, oceanography and, in modern settings, anthropogenic impacts. Compared with small, gravel-bedded river systems, less is known about large, sandy‐bed rivers, particularly from the river source to marine sink. In the present study, we examine longitudinal changes in sediment grain size along the middle and lower Yangtze River, downstream of the Three Gorges Dam (TGD), and along the major sediment dispersal pathway into the East China Sea, over a total length of 2100 km. We also examine the spatial patterns of seabed sediment grain size in the East China Sea adjacent to the Yangtze Estuary (70,000 km 2 in area). In particular, we consider the impact of the TGD on the grain size of the riverbed and seabed sediments. Before the construction of the TGD, the relationship between median grain size and distance along the sandy bed of the middle and lower Yangtze showed a downstream fining trend that was exponential in form. After the TGD was built, erosion caused an abrupt gravel–sand transition to develop in the section immediately downstream of the TGD. In the Yangtze Estuary, flocculation and subsequent deposition of suspended riverine mud during the slack water period between flood and ebb tides led to the formation of an abrupt sand–mud transition. Muddy deposits along the major longshore sediment dispersal route also show an exponential fining trend. However, towards the open East China Sea, the modern riverine muds are replaced seawards by older sands. The mud margin there was found to have retreated landward significantly over the post-TGD period due to erosion driven by the significant decrease in sediment supply from the Yangtze River. We expect that the impact of the TGD on the grain size of bed sediments in the Yangtze River and the East China Sea will continue for some time, and the change in the grain size of bed sediments there will become more pronounced.