[Factors Influencing the Variation in Phytoplankton Functional Groups in Fuchunjiang Reservoir].

To explore the distribution characteristics, blooming risk mechanism and driving factors of phytoplankton community structure in Fuchunjiang Reservoir. The variation characteristics of phytoplankton, zooplankton and physicochemical indicators in Fuchunjiang Reservoir and its upper and lower reaches were investigated in 2020 and 2021. Based on the phytoplankton functional groups, non-metric multidimensional scale analysis, redundancy analysis and other statistical methods, the seasonal succession characteristics and driving factors of phytoplankton functional groups were analyzed. A total of 18 phytoplankton functional groups were identified, in of which 10 were predominant. The composition of phytoplankton functional groups in the Fuchunjiang Reservoir was significant different. Spatially, the upstream were dominated by group C and P while the represent species were Cyclotella and Aulacoseira,reflecting the mixed meso-eutrophic environments. However, group P was the main group in Fuchunjiang reservoir, and the dominance decreased gradually along the stream direction. Meanwhile, in the downstream, MP has an absolute advantage at Qiantang River estuary. It reflected the environmental characteristics of frequent disturbance and high turbidity of tide-sensing rivers. In addition, the predominant functional groups demonstrated strong seasonal variations. The dominant functional groups were diverse in summer and consisted of P+L0+J+M+S1+H1+MP. In addition to group P (Aulacoseira), which was dominant throughout the year, it also included several groups represented by cyanobacteria and chlorophyta, reflecting the environmental characteristics of changeable habitats and vigorous productivity. In autumn, the succession was dominated by H1 group represented by Dolichospermum and the representative function groups were P and H1, reflecting the hydrological background of reduced flow and static flow. In winter, the increase of Cyclotella led to the predominance of group C, which was dominated by P+C, reflecting the changing conditions of weakened water exchange and intensified eutrophication problems. In spring, the dominant functional groups were gradually enriched and were composed of C, D, P, and MP, which also reflected the changing environmental habitat characteristics which caused by increasing rainfall and air temperature. According to the results of the C-R-S growth strategy, the Fuchunjiang Reservoir has been in the R strategy for a long time, which was consistent with the habitat characteristics of Fuchunjiang Reservoir and its upper and lower reaches with high disturbance and low stress. In addition, C strategy and S strategy appeared in some reaches, reflecting the variability of water quality and hydrology. RDA analysis showed that water temperature, discharge, zooplankton biomass, permanganate index, total nitrogen and total phosphorus were significantly correlated with the seasonal succession of phytoplankton functional groups (P < 0.05), and temperature and flow pattern were probably the most critical factors for the succession. Studies have shown that the impact of hydrometeorological processes on phytoplankton in the Fuchunjiang Reservoir is crucial:high temperature and changing discharge during the summer may lead to cyanobacterial blooms in the Fuchunjiang reservoir; To reduce the risk of algal blooms, it is still necessary to increase the control of nitrogen and phosphorus load in rivers, and fully consider the coordination of water conservancy dispatch methods.

LW-213 induces immunogenic tumor cell death via ER stress mediated by lysosomal TRPML1.

Dying tumor cells release biological signals that exhibit antigenicity, activate cytotoxic T lymphocytes, and induce immunogenic cell death (ICD), playing a key role in immune surveillance. We demonstrate that the flavonoid LW-213 activates endoplasmic reticulum stress (ERS) in different tumor cells and that the lysosomal calcium channel TRPML1 mediates the ERS process in human cellular lymphoma Hut-102 cells. Apoptotic tumor cells induced by ERS often possess immunogenicity. Tumor cells treated with LW-213 exhibit damage-associated molecular patterns (DAMPs), including calreticulin translocation to the plasma membrane and extracellular release of ATP and HMGB1. When co-cultured with antigen-presenting cells (APCs), LW-213-treated tumor cells activated APCs. Two groups of C57BL/6J mice were inoculated with Lewis cells: a "vaccine group", which demonstrated that LW-213-treated tumor cells promote the maturation of dendritic cells and increase CD8+ T cells infiltration in the tumor microenvironment and a "pharmacodynamic group", treated with a combination of LW-213 and PD1/PD-L1 inhibitor (BMS-1), which reduced tumor growth and significantly prolonged the survival time of mice in the "pharmacodynamic group". Therefore, LW-213 can be developed as a novel ICD inducer, providing a new concept for antitumor immunotherapy.

[Influence of Denitrification on Cyanobacterial Blooms Trends in Lake Taihu, China].

Denitrification is a major process in aquatic ecosystems, and it competes with cyanobacterial growth for nitrogen. However, the effect of denitrification on cyanobacterial blooms under the background of climate change remains unclear. This study explored the interaction between lake denitrification and formation of cyanobacterial blooms, using the historical water quality monitoring data of North Lake Taihu over five years from 2017 to 2021 and via incubation experiments of cyanobacteria and sediment denitrification. The monitoring data showed that algal biomass (Chla as a proxy) primarily peaked during summer and autumn. The seasonal variations in total N concentration showed a completely opposite trend than that of algal biomass, which peaked in winter and spring. Nitrate was the major component of dissolved inorganic nitrogen, and the nitrate concentration was approximately zero in summer and autumn. The total phosphorus concentration varied in the same way as the Chla concentration. The experimental results showed that Cyanobacteria did not grow when the temperature was below 20℃. In comparison, denitrification showed a significant linear relationship with temperatures between 10-25℃ (R2=0.99) and reached the maximum value of (62.98±21.36) µmol·(kg·h)-1 in Lake Taihu at 25℃. Additionally, the nitrate concentration threshold at the maximum denitrification rate was 4 mg·L-1. Cyanobacteria assimilate nitrate for growth, thereby reducing the concentration of nitrate required for denitrification. This study indicated that the advance in lake temperature warming due to climate change may result in earlier growth of cyanobacteria, thereby leading to large amounts of N being assimilated by algae before denitrification, further affecting the dynamics of cyanobacterial blooms. The present results are scientifically important for explaining the mechanism of cyanobacterial bloom rebound in Lake Taihu under the background of recent climate changes.

Polysulfide Protects Against Diabetic Cardiomyopathy Through Sulfhydration of Peroxisome Proliferator-Activated Receptor-γ and Sirtuin 3.

Aims: Diabetic cardiomyopathy (DCM) is characterized by cardiac dysfunction and heart failure. However, the effective therapy for DCM is still lacking. Polysulfide contains chains of sulfur atoms, and accumulative evidence has shown that it actively participates in mammalian physiology or pathophysiology. Nevertheless, the potential effects and mechanisms of polysulfide in DCM need further investigation. In the present study, Na2S4, a polysulfide donor, was employed to investigate the therapeutic effects of polysulfide in DCM. Results: Our results showed that Na2S4 protected cardiomyocytes against high glucose (HG)-induced cardiomyocyte injury. The pathological changes in DCM including cell death, oxidative stress, mitochondrial dysfunction and cardiac hypertrophy were improved by Na2S4 treatment. The left ventricular contractile function in streptozotocin (STZ)-induced diabetic mice was significantly improved by Na2S4. Mechanistically, Na2S4 upregulated and sulfhydrated peroxisome proliferator-activated receptor-γ (PPARγ) and sirtuin 3 (SIRT-3) in cardiomyocytes. Suppression of PPARγ or SIRT-3 with their specific inhibitors or blockade of sulfhydration abolished the protective effects of Na2S4. Moreover, mutations of PPARγ or SIRT-3 at specific cysteines diminished the benefits of Na2S4 in HG-challenged cardiomyocytes. Innovation and Conclusion: We demonstrated that Na2S4 prevented the development of DCM via sulfhydration of both PPARγ and SIRT-3. Our results imply that polysulfide may be a potential and promising agent to treat DCM. Antioxid. Redox Signal. 38, 1-17.

[Effects of Land Use on Nutrient Concentrations in the Inflow River of Lake Taihu, China].

Land use is an important factor affecting non-point nutrient loading. Here, the Wuxi River basin was selected to analyze the influence of sub-basin land use on nutrient concentrations using remotely sensed land use data and monthly river water quality variables from October 2019 to September 2020. The results showed that the water quality of the river was closely related to land-use type. Specifically, dryland farmland, villages, and building land have a strong promoting influence on nitrogen, phosphorus, organic carbon, and phytoplankton chlorophyll a. The proportion of orchard land was also positively correlated with river nutrient concentrations. A negative correlation was observed between the proportion of forest land and nutrient concentrations. Moreover, the proportion of the water area in rivers and reservoirs was negatively correlated with the total dissolved nitrogen and nitrate concentrations in the river, and the proportion of the water area in natural pits and fishponds was negatively correlated with river nitrate and ammonia concentrations. Furthermore, the proportion of river and fishpond areas was positively correlated with the concentration of dissolved total phosphorus, dissolved organic carbon, and the permanganate index, while the proportion of the natural pond area was positively correlated with the concentration of particulate phosphorus and phytoplankton chlorophyll a. The influence of land-use types on water quality was also affected by distance from the river. This research indicates that the appropriate utilization of land and wetlands is key to controlling non-point nutrient loading in the river network, including Lake Taihu. Specifically, the self-purification capacity of wetland waters should be incorporated into nutrient control schemes, and special attention should be paid to the reduction of non-point source pollution in the drylands along the downstream riverbanks and urbanized areas.

[Long-term Changes and Drivers of Ecological Security in Shahe Reservoir, China].

Monthly datasets of ecological indicators from 2010 to 2020 in Shahe Reservoir, Tianmuhu, China, were examined to reveal the long-term variations in water ecological security and its driving factors. The results of Secchi disk depth(SD) measurements revealed significantly spatial variation(P<0.05) within the reservoir. The highest SD was recorded in the downstream-linked reservoir, and the lowest SD was recorded in the upstream tributaries. In contrast, the values of other water ecological indicators were higher in the upstream tributaries than in the transition region and the downstream-linked reservoir area. In summer and autumn, the SD was low, while the concentrations of total phosphorous(TP), chlorophyll a(Chl-a), the permanganate index, and cyanobacterial biomass(BMc) were high. During the thermal stratification period from May to September, the concentrations of 2-methylisoborneol(MIB) and Chl-a were highest at a depth of 4 m, while diatom biomass(BMb) and BMc reached their maximum at depths of 2 m and 0.5 m, respectively. Therefore, spatial and temporal variations should be fully considered when evaluating aquatic ecological security. Focusing on spring and summer, when the risk of water ecological security was high, Chl-a combined with SD and MIB along with their correlation with other water quality indexes, was used to evaluate and optimize the ecological security of Shahe Reservoir. The evaluation results showed that the aquatic ecological security of the reservoir was excellent over the last 10 years; however, annual fluctuations have been large and the evaluation scores were spatially variable. While seasonal sampling strategies focusing on three layers depths are economical and reliable for lake regions with thermal stratification, our results indicate that tailored monitoring may be required to determine the aquatic ecological security of lakes and reservoirs. In Shahe Reservoir, the decrease in the SD and the increase in MIB caused by high TP and algal blooms were the most important drivers of ecological service function in the reservoir. Furthermore, hydrometeorological factors may also play important roles in the aquatic ecological security of reservoirs.

[Spatial Differences and Influencing Factors of Denitrification and ANAMMOX Rates in Spring and Summer in Lake Taihu].

Denitrification and ANAMMOX are the main nitrogen removal processes in lakes, which are of great significance for maintaining the nitrogen balance. Lake Taihu is a large, shallow lake. There are great spatial and temporal differences in the nutrient levels and algal blooms, which will affect the rates of denitrification and ANAMMOX. In order to understand the spatial and temporal variations in the denitrification and ANAMMOX rates and their influencing factors in Lake Taihu, undisturbed sediment cores were collected from Meiliang Bay, Gonghu Bay, Zhushan Bay, Dapukou Bay, Xukou Bay, and the center of Lake Taihu in the spring and summer of 2020. The results showed that the spatial distribution of the denitrification and ANAMMOX rates varied greatly in different areas of Lake Taihu in spring. The denitrification and ANAMMOX rates were (27.74±8.45)-(142.43±35.54) µmol·(m2·h)-1 and (2.35±1.06)-(17.95±8.66) µmol·(m2·h)-1, respectively. The contribution of ANAMMOX to nitrogen removal was relatively low, ranging from (7.82±1.71)% to (11.20±1.53)%. In summer, the denitrification and ANAMMOX rates were (165.68±62.14) µmol·(m2·h)-1 and (33.56±10.66) µmol·(m2·h)-1, respectively. The nitrogen removal rates were relatively low in other areas where the denitrification and ANAMMOX rates were (25.47±10.46)-(42.50±16.46) µmol·(m2·h)-1 and (2.65±0.94)-(5.95±2.65) µmol·(m2·h)-1, respectively. The contribution of ANAMMOX to nitrogen removal was (13.62±1.95)%-(7.24±1.78)%. The denitrification rate in summer was generally lower than that in spring, while the ANAMMOX rate did not decrease significantly compared with that in spring. The statistical analysis showed that the denitrification and ANAMMOX rates were significantly correlated with the substrate nitrogen concentration (P<0.01), which indicated that the nitrogen concentration was the main factor causing the difference in the nitrogen removal rates in different lake regions. In addition, there was a significant positive correlation between the contribution rate of ANAMMOX and the concentration of chlorophyll-a (P<0.05), thereby indicating that cyanobacteria blooms have a great influence on the change in the contribution of ANAMMOX to nitrogen removal.

[Changes in Algal Particles and Their Water Quality Effects in the Outflow River of Taihu Lake].

Connected rivers are a common engineering method to ensure the ecological health of urban water. However, for the lakes with serious cyanobacteria blooms, the algal particles are carried by the outflow of the lake and will have a significant impact on water quality. The location at which the Liangxi river meets Meiliang Bay of Lake Taihu was selected to explore the influence of the eutrophic lake on the connected rivers, and high-frequency monitoring was conducted in summer for three consecutive years to analyze the changes in the flux of cyanobacterial bloom particles in rivers and their impact on river water quality. The results show that:① The improvement of the algal cyanobacteria bloom in Meiliang Bay and the operation of the pressure-controlled algae well at the entrance of the river significantly reduced the concentration of chlorophyll a and the flux of algae particles in the Liangxi River. The average value of the concentration of chlorophyll a and the flux of algae particles in the river in summer 2019 were 54.34 µg·L-1 and 84.7 t·d-1, respectively, and significantly lower than those of 2017; ② Water diversion had a significant effect on improving the water quality of the receiving water. Except for DTP, the nitrogen and phosphorus concentrations of the remaining forms of the Liangxi River showed a downward trend from 2017 to 2019, indicating that the water quality of the Liangxi river improved after water transfer; ③ A large amount of cyanobacterial blooms entering the channel significantly increased the particulate nitrogen and phosphorus content of the water. From 2017 to 2019, the nitrogen and phosphorus in the Liangxi River were mainly PN and PP, accounting for 62.5% and 70.8% of TN and TP, respectively; ④ The water quality of the Beijing-Hangzhou Grand Canal and other connected rivers has not been affected by the algal particles in Meiliang Bay. In August 2019, the chlorophyll a content in the canal water decreased by 65% compared with that of June, indicating that cyanobacterial bloom particles have not accumulated in the Grand Canal; ⑤ On the premise that the cyanobacteria bloom in the lake has not been effectively improved, the algae particles carried by the water diversion will have an impact on the water quality and landscape of the local reach connecting the river.

LW-213 induces cell apoptosis in human cutaneous T-cell lymphomas by activating PERK-eIF2α-ATF4-CHOP axis.

Cutaneous T-cell lymphoma (CTCL) is characterized by a heterogeneous group of extranodal non-Hodgkin lymphomas, in which monoclonal T lymphocytes infiltrate the skin. LW-213, a derivative of wogonin, was found to induce cell apoptosis in chronic myeloid leukemia (CML). In this study, we investigated the effects of LW-213 on CTCL cells and the underlying mechanisms. We showed that LW-213 (1-25 µM) dose-dependently inhibited human CTCL cell lines (Hut-102, Hut-78, MyLa, and HH) with IC50 values of around 10 µM, meanwhile it potently inhibited primary leukemia cells derived from peripheral blood of T-cell lymphoma patients. We revealed that LW-213-induced apoptosis was accompanied by ROS formation and the release of calcium from endoplasmic reticulum (ER) through IP3R-1channel. LW-213 selectively activated CHOP and induced apoptosis in Hut-102 cells via activating PERK-eIF2α-ATF4 pathway. Interestingly, the degree of apoptosis and expression of ER stress-related proteins were alleviated in the presence of either N-acetyl cysteine (NAC), an ROS scavenger, or 2-aminoethyl diphenylborinate (2-APB), an IP3R-1 inhibitor, implicating ROS/calcium-dependent ER stress in LW-213-induced apoptosis. In NOD/SCID mice bearing Hut-102 cell line xenografts, administration of LW-213 (10 mg/kg, ip, every other day for 4 weeks) markedly inhibited the growth of Hut-102 derived xenografts and prolonged survival. In conclusion, our study provides a new insight into the mechanism of LW-213-induced apoptosis, suggesting the potential of LW-213 as a promising agent against CTCL.

Polysulfide-mediated sulfhydration of SIRT1 prevents diabetic nephropathy by suppressing phosphorylation and acetylation of p65 NF-κB and STAT3.

Diabetic kidney disease is known as a major cause of chronic kidney disease and end stage renal disease. Polysulfides, a class of chemical agents with a chain of sulfur atoms, are found to confer renal protective effects in acute kidney injury. However, whether a polysulfide donor, sodium tetrasulfide (Na2S4), confers protective effects against diabetic nephropathy remains unclear. Our results showed that Na2S4 treatment ameliorated renal dysfunctional and histological damage in diabetic kidneys through inhibiting the overproduction of inflammation cytokine and reactive oxygen species (ROS), as well as attenuating renal fibrosis and renal cell apoptosis. Additionally, the upregulated phosphorylation and acetylation levels of p65 nuclear factor κB (p65 NF-κB) and signal transducer and activator of transcription 3 (STAT3) in diabetic nephropathy were abrogated by Na2S4 in a sirtuin-1 (SIRT1)-dependent manner. In renal tubular epithelial cells, Na2S4 directly sulfhydrated SIRT1 at two conserved CXXC domains (Cys371/374; Cys395/398), then induced dephosphorylation and deacetylation of its targeted proteins including p65 NF-κB and STAT3, thereby reducing high glucose (HG)-caused oxidative stress, cell apoptosis, inflammation response and epithelial-to-mesenchymal transition (EMT) progression. Most importantly, inactivation of SIRT1 by a specific inhibitor EX-527, small interfering RNA (siRNA), a de-sulfhydration reagent dithiothreitol (DTT), or mutation of Cys371/374 and Cys395/398 sites at SIRT1 abolished the protective effects of Na2S4 on diabetic kidney insulting. These results reveal that polysulfides may attenuate diabetic renal lesions via inactivation of p65 NF-κB and STAT3 phosphorylation/acetylation through sulfhydrating SIRT1.

[Effect of Heavy Rainfall on Nitrogen and Phosphorus Concentrations in Rivers at River-net Plain].

To understand the quantitative effect of heavy rain on nitrogen and phosphorus pollution in river-net plain, daily observations of nutrient concentrations in two rivers, flowing into Lake Taihu, were conducted from 1st September, 2017 to 31st August, 2019. The daily rainfall was recorded by auto-recording meteorological stations located on the two rivers and the Taihu Laboratory for Lake Ecosystem Research. Intensive sampling in different sections of the two rivers during Super Typhoon Lekima was also conducted in August 2019. Using these datasets, the influence of heavy rainfall on various forms of nitrogen and phosphorus concentrations in the rivers, and its environmental effects, were analyzed. The results showed that 16 heavy rainfall events (19 d) were observed in two years, 50% of which occurred in the summer season. In addition, heavy rainfall accounted for as much as 41.33% of the total rainfall over the entire year. After the period of heavy rainfall, the concentrations of various forms of nitrogen and phosphorus increased, and the particulate P generally exhibited the fastest response, usually peaking on the day of heavy rainfall. In contrast, the peaks of N were delayed for 2-5 days with the occurrence of heavy rain. In general, the duration of the increase in the concentration of nutrients in the study river caused by heavy rainfall was short (usually 1-2 days), and sometimes was lower than the concentration before the rains. The Dapu River exhibited a slower response to heavy rains than the Yincun River because it has a larger and longer catchment area than the Dapu River. In addition, the effect of heavy rain on N and P concentrations was also strongly influenced by the land-use situation around the river basin. The increase of nitrogen in the reach, affected by agricultural non-point sources, was dominated by granular nitrogen, and the increase of nitrogen in the reach affected by urban non-point sources was dominated by dissolved nitrogen. The increase of phosphorus was dominated by granular phosphorus in the entire process. The conclusions of this study are as follows:In the plain river network area, the fluctuations of nitrogen and phosphorus concentrations in the river water body caused by heavy rainfall are small, and the response of various forms of nitrogen and phosphorus are significantly affected by the local environmental background. Therefore, the water quality generally exhibited limited variation. Due to the large proportion of water entering the lake during heavy rainfall events, a high level of the nutrient loading was also observed, and the occurrence of heavy rainfall was occasional. The short-term effect of heavy rainfall on the nitrogen and phosphorus loading entering the lake in the river channel in the plain river network area is therefore, also significant, and requires further investigation.

[Spatial-temporal Variations and Driving of Nitrogen and Phosphorus Ratios in Lakes in the Middle and Lower Reaches of Yangtze River].

In spring and summer of 2018, 26 lakes in the middle and lower reaches of the Yangtze River were studied to determine the temporal and spatial characteristics of nitrogen and phosphorus ratios (TN/TP) and their influencing factors. The differences in nitrogen and phosphorus ratios in different types of lakes (including water-psaaing lakes, deep reservoirs and eutrophic lakes) and in different seasons were analyzed in terms of the sources of the lakes, lake depth, suspended particulate matter concentrations, and phytoplankton levels. The average TN/TP was 21.52±14.28 in spring and 21.73±23.78 in summer. The TN/TP varied significantly in different types of lakes. The TN/TP ratios in water-passing lakes, deep reservoirs and eutrophic lakes were 20.41±9.25, 40.97±33.37, and 14.38±7.40 during spring, and were 22.62±6.48, 96.38±45.91, and 10.91±4.44 during summer, respectively. The TN/TP of the water-passing lakes and deep reservoirs increased significantly in summer, while that of the eutrophic lakes decreased significantly, which indicates that TN/TP changes and lake nutritional status are closely related. The source of nutrients in lakes and reservoirs affects the TN/TP. The TN/TP of lakes and reservoirs had a significant correlation with the lake depth in both spring and summer, indicating that lake depth is a key factor affecting the ratio of nitrogen and phosphorus. In addition, in eutrophic lakes with higher absolute nutrient concentrations, TN/TP has less effect on phytoplankton, while in deep-water lakes with lower absolute nutrient concentrations, TN/TP can determine the growth of phytoplankton limited by phosphorus. Therefore, the governance strategy of lakes in the middle and lower reaches of the Yangtze River should prioritize phosphorus control. Local digging, controlling non-point source pollution, sediment dredging, and changing fishery production methods can be applied to improve the ecological quality of the eutrophic lakes.

[Influence of Potamogeton crispus on Lake Water Environment and Phytoplankton Community Structure].

The decomposition of submerged macrophytes is generally associated with dramatic changes in the water environment, such as the large release of nutrients (e.g., nitrogen and phosphorus) and organic carbon to the surrounding waters, which may result in significant changes in phytoplankton community structure. In this study, Potamogeton crispus, physicochemical variables, and phytoplankton samples were collected in 14 shallow lakes in the middle and lower Jianghuai Plain in spring (growing period of P. crispus) and summer (decomposition phase of P. crispus) of 2018. The effects of the decline of P. crispus on water quality and phytoplankton community structure were quantified. The results showed that water transparency increased significantly in spring because the growth of P. crispus inhibits sediment resuspension and macrophytes can transport the nutrients from the water column to the sediment. The values of dissolved oxygen and pH also increased significantly due the photosynthesis by macrophytes. In contrast, the decomposition of P. crispus during summer months caused a significant increase in water turbidity and organic matter. There were considerable differences in phytoplankton biomass and cyanobacterial biomass in the sites with or without P. crispus, and the corresponding ratios of cyanobacterial biomass to the total algal biomass were 18.96% and 34.05%, respectively. Higher values of cyanobacterial biomass were observed with the decomposition of P. crispus than its counterpart in summer because ① the decomposition of macrophytes provided sufficient organic matter and nutrient (nitrogen and phosphorus) resources for cyanobacterial growth; ② P. crispus decline in summer significantly increased water turbidity, which makes cyanobacteria occupy a better ecological niche and more efficiently utilize nitrogen and phosphorus.

[High-Frequency Dynamics of Water Quality and Phytoplankton Community in Inflowing River Mouth of Xin'anjiang Reservoir, China].

The tail of the reservoir is the unstable zone regarding water quality and phytoplankton community. Therefore, it is the crucial zone in aquatic ecosystem transitions. To understand the transition characteristics and driving mechanisms of water environment dynamics, high-frequency monitoring of the water environment and phytoplankton community in the tail of a deep and large reservoir, the Xin'anjiang Reservoir in southeast of China, was conducted using a water quality monitoring buoy and three-day interval water sampling during 18 months. Results show clear seasonal thermal and oxygen stratification in the river mouth of the reservoir. The nutrient and chlorophyll-a concentrations also show stratifying phenomena during the thermal stratification period. Heavy rain and inflow quickly consume the stratification. Nutrient concentrations were highly dynamic in the river mouth. The total phosphorus ranges from 0.011 mg·L-1 to 0.188 mg·L-1, and total nitrogen ranges from 0.75 mg·L-1 to 2.76 mg·L-1. Dissolved phosphorus comprised 56% of total phosphorus, and dissolved nitrogen occupied 88% of total nitrogen, respectively. Nutrient concentrations were influenced strongly by rainfall intensity and inflow rate. Total phosphorus and nitrogen concentrations were significantly related to the three-day accumulated rainfall. Nutrient concentrations in the flood season (March to June) were significantly higher than in the non-flood season (P<0.001). Seasonal phytoplankton proliferation also significantly influenced by total phosphorus concentration. The phytoplankton community changes significantly with seasons and flood events. Bacillariophytea was generally dominant throughout the year, with the predominant genus of Fragilaria spp., Cyclotella spp., Synedra spp., and Melosira spp. Cyanophyta biomass peaked in July, August, and September, with the dominant genus of Aphanizomenon spp., Microcystis spp., and Oscillatoria spp. Apart from the high temperature, storm inflow events also triggered Cyanophyta proliferation. The proliferation of Chlorophyta was similar to Cyanophyta, with the predominant genus of Pediastrum spp. and Closterium spp.. While the Cryptophyta biomass peaked during March to May, with the predominant genus of Cryptomonas spp.. Redundancy analysis shows that the influence factors of phytoplankton community dynamics include the inflow rate, temperature, water level, water transparency, total nitrogen, total phosphorus, and nitrogen to phosphorus ratio. The meteorological and hydrological factors were major factors for phytoplankton dynamics during later autumn and winter, while the nutrient will be the co-driving factors of phytoplankton community dynamics during summer and early autumn. The research confirmed the huge influence of the intensity rainfall event on the water environment in reservoirs and described the key environmental conditions for phytoplankton community dynamics. The research is useful for the design of the monitoring and forecasting system for water safety in drinking water source reservoirs.

[Influence of Nutrient Pulse Input on Nitrogen and Phosphorus Concentrations and Algal Growth in the Sediment-Water System of Lake Taihu].

Lake sediments not only act as a reservoir of nutrients, but are also a source of secondary pollution of nutrients for overlying water, which can buffer the variations in nutrients in overlying water and affect nutrient bioavailability and algal growth. In the current study, a simulation experiment was conducted using sediment cores collected in Meiliang Bay. Our aim was to elucidate the effect of nitrogen (N) and phosphorus (P) pulse input on variations in the water nutrient level and algal growth. We also clarified the migration and redistribution process of N and P between the sediment overlying water and algae. The results showed that the concentration of N in overlying water of the treatment group (with sediment) was much lower than that in controls (no sediment) when N was input at a pulse rate of 0.30 mg·(L·d)-1. The loss rate of N in the overlying water of the treatment group ranged from 0.144 mg·(L·d)-1 to 0.156 mg·(L·d)-1 and that in the control ranged from 0.021 mg·(L·d)-1to 0.039 mg·(L·d)-1. On the contrary, the denitrification rate of overlying water in the treatment group ranged from 40.793 mg·(m2·d)-1 to 44.193 mg·(m2·d)-1, accounting to 48%-52% of the external N loading. In contrast, the denitrification rate of overlying water in controls was from 0.021 mg·(L·d)-1to 0.039 mg·(L·d)-1, only accounting for 7%-13% of the external N loading. These results indicated that the sediment-water interface is the main site of denitrification in shallow lakes and plays an essential role in reducing N pollution in lakes. With respect to the pulse input of P at a rate of 0.015 mg·(L·d)-1, the majority of P (about 52%-58%) was imported into the sediment at a rate from 2.210 mg·(m2·d)-1to 2.422 mg·(m2·d)-1, and only a small proportion, approximately 23%-26%, was utilized by algae. The remaining P existed in overlying water in a dissolved state. These results implied that the sediment can buffer the external P input as an obvious "sink" effect of nutrients. Our results also showed that the sediment acts as a "source" of P when no external P was added. The release rate of P from the sediment to overlying water was from 0.310 mg·(m2·d)-1 to 0.468 mg·(m2·d)-1. In situ high-resolution analysis of ZrO-Chelex DGT showed that the DGT-P concentration in the interstitial water was much higher than that in the overlying water, and the concentration of DGT-P was significantly correlated with the concentration of DGT-Fe in interstitial water. These results indicate that changes in the redox potential may cause considerable release of internal phosphorus. In summary, our study showed that internal P in sediments can be released into the overlying water and support the growth of algae when the external nutrients are controlled. As a result, a delayed response was observed in the nutrient concentration in overlying water to external P reduction. Therefore, the dual control of N and P may have a better practical application to mitigate cyanobacteria blooms in shallow lakes.

[Spatial-temporal Distribution of Suspended Solids and Its Sedimentation Flux and Nutrients Effects in Xin'anjiang Reservoir, China].

To analyze the spatial-temporal distribution and sedimentation characteristics of suspended solids in reservoirs, high-frequency monitoring of a sediment trap and buoy, combined with three-dimensional water sampling, was conducted and analyzed in Xin'anjiang Reservoir for a year. The results showed that the turbidity data of the buoy has significant correlation with rainfall, inflow, and suspended solids (SS), particularly for SS (P<0.01, R2=0.86). There is an obvious spatial difference in SS between spring and summer, when the rainfall season occurs (river area > transition area > lake area). However, there is little difference in SS concentration between autumn and winter. There is a spatial trend of river area > transition area > lake area (with rates of 27.82, 4.34, and 0.26 g·(m2·d)-1, respectively), and a temporal trend of spring and summer > autumn and winter. The sedimentation flux of the whole lake is 2.57×106 t·a-1 combined with the investigation of the four-season SS at 60 points across the whole lake, and the settlement flux in spring and summer is higher than that in autumn and winter. The contents of particulate nitrogen (PN) in JK, XJS, and DB were 6812, 15886, and 21986 mg·kg-1, and the particulate phosphorus (PP) contents were 2545, 3269, and 3077 mg·kg-1, respectively. Statistical analysis shows that there is a good exponential relationship between moderate rainfall and turbidity growth rate in the river area of the reservoir (R2=0.81). Moreover, the continuous heavy rainfall affects turbidity in river area, but has little effect on the transition area. The concentration of SS has a good exponential decay with distance from the river to the dam (R2=0.84), especially in spring and summer. Research shows that the average annual deposition rate in Xin'anjiang Reservoir is 0.07%, lower than other large reservoirs in the country; however, there are certain risks in front of the dam because the nutrient sediments are high. The results suggest that reservoir managers should pay attention to water and soil conservation in the watershed to reduce the impact of rainfall on reservoir water quality. Meanwhile, the potential nutrient internal release risk in the downstream area before the dam should be considered.

DR-region of Na+/K+-ATPase is a target to ameliorate hepatic insulin resistance in obese diabetic mice.

Reduced hepatic Na+/K+-ATPase (NKA) activity and NKAα1 expression are engaged in the pathologies of metabolism diseases. The present study was designed to investigate the potential roles of NKAα1 in hepatic gluconeogenesis and glycogenesis in both hepatocytes and obese diabetic mice. Methods: Insulin resistance was mimicked by glucosamine (GlcN) in either human hepatocellular carcinoma (HepG2) cells or primary mouse primary hepatocytes. Obese diabetic mice were induced by high-fat diet (HFD) feeding for 12 weeks. Results: We found that both NKA activity and NKAα1 protein level were downregulated in GlcN-treated hepatocytes and in the livers of obese diabetic mice. Pharmacological inhibition of NKA with ouabain worsened, while activation of NKAα1 with an antibody against an extracellular DR region of NKAα1 subunit (DR-Ab) prevented GlcN-induced increase in gluconeogenesis and decrease in glycogenesis. Likewise, the above results were also corroborated by the opposite effects of genetic knockout/overexpression of NKAα1 on both gluconeogenesis and glycogenesis. In obese diabetic mice, hepatic activation or overexpression of NKAα1 stimulated the PI3K/Akt pathway to suppress hyperglycemia and improve insulin resistance. More importantly, loss of NKA activities in NKAα1+/- mice was associated with more susceptibility to insulin resistance following HFD feeding. Conclusions: Our findings suggest that NKAα1 is a physiological regulator of glucose homoeostasis and its DR-region is a novel target to treat hepatic insulin resistance.

Role of nitroxyl (HNO) in cardiovascular system: From biochemistry to pharmacology.

Cardiovascular diseases are recognized to be a major cause of people morbidity and mortality. A host of stress signals contribute to the pathogenesis of cardiovascular disorders. Deficiency of hydrogen sulfide (H2S) or nitric oxide (NO) coordinately plays essential roles in the development of cardiovascular diseases. Recent studies have shown that interaction between the two gaseostransmitters, H2S and NO, may give rise to nitroxyl (HNO), one-electron-reduced product of NO. HNO is found to exhibit a variety of biological and pharmacological properties including positive inotropy and cardiovascular protective effects, etc. In this review, recent progresses regarding HNO generation, detection, biochemical and pharmacological functions are discussed.

Induction of caveolin-3/eNOS complex by nitroxyl (HNO) ameliorates diabetic cardiomyopathy.

Nitroxyl (HNO), one-electron reduced and protonated sibling of nitric oxide (NO), is a potential regulator of cardiovascular functions. It produces positive inotropic, lusitropic, myocardial anti-hypertrophic and vasodilator properties. Despite of these favorable actions, the significance and the possible mechanisms of HNO in diabetic hearts have yet to be fully elucidated. H9c2 cells or primary neonatal mouse cardiomyocytes were incubated with normal glucose (NG) or high glucose (HG). Male C57BL/6 mice received intraperitoneal injection of streptozotocin (STZ) to induce diabetes. Here, we demonstrated that the baseline fluorescence signals of HNO in H9c2 cells were reinforced by both HNO donor Angeli's salt (AS), and the mixture of hydrogen sulfide (H2S) donor sodium hydrogen sulfide (NaHS) and NO donor sodium nitroprusside (SNP), but decreased by HG. Pretreatment with AS significantly reduced HG-induced cell vitality injury, apoptosis, reactive oxygen species (ROS) generation, and hypertrophy in H9c2 cells. This effect was mediated by induction of caveolin-3 (Cav-3)/endothelial nitric oxide (NO) synthase (eNOS) complex. Disruption of Cav-3/eNOS by pharmacological manipulation or small interfering RNA (siRNA) abolished the protective effects of AS in HG-incubated H9c2 cells. In STZ-induced diabetic mice, administration of AS ameliorated the development of diabetic cardiomyopathy, as evidenced by improved cardiac function and reduced cardiac hypertrophy, apoptosis, oxidative stress and myocardial fibrosis without affecting hyperglycemia. This study shed light on how interaction of NO and H2S regulates cardiac pathology and provide new route to treat diabetic cardiomyopathy with HNO.

LW-213, a newly synthesized flavonoid, induces G2/M phase arrest and apoptosis in chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell neoplasm characterized by an uncontrolled proliferation of moderately and well differentiated cells of the granulocytic lineage. LW-213, a newly synthesized flavonoid compound, was found to exert antitumor effects against breast cancer through inducing G2/M phase arrest. We investigated whether LW-213 exerted anti-CML effects and the underlying mechanisms. We showed that LW-213 inhibited the growth of human CML cell lines K562 and imatinid-resistant K562 (K562r) in dose- and time-dependent manners with IC50 values at the low µmol/L levels. LW-213 (5, 10, 15 µM) caused G2/M phase arrest of K562 and K562r cells via reducing the activity of G2/M phase transition-related proteins Cyclin B1/CDC2 complex. LW-213 treatment induced apoptosis of K562 and K562r cells via inhibiting the expression of CDK9 through lysosome degradation, thus leading to the suppression of RNAPII phosphorylation, down-regulation of a short-lived anti-apoptic protein MCL-1. The lysosome inhibitor, NH4Cl, could reverse the anti-CML effects of LW-213 including CDK9 degradation and apoptosis. LW-213 treatment also degraded the downstream proteins of BCR-ABL1, such as oncoproteins AKT, STAT3/5 in CML cells, which was blocked by NH4Cl. In primary CML cells and CD34+ stem cells, LW-213 maintained its pro-apoptotic activity. In a K562 cells-bearing mice model, administration of LW-213 (2.5, 5.0 mg/kg, ip, every other day for 4 weeks) dose-dependently prolonged the survival duration, and significantly suppressed huCD45+ cell infiltration and expression of MCL-1 in spleens. Taken together, our results demonstrate that LW-213 may be an efficient agent for CML treatment.