Polygalacin D inhibits the growth of hepatocellular carcinoma cells through BNIP3L-mediated mitophagy and endogenous apoptosis pathways.

Platycodon grandiflorum (Jacq.) A. DC. is a famous medicinal plant commonly used in East Asia. Triterpene saponins isolated from P. grandiflorum are the main biologically active compounds, among which polygalacin D (PGD) has been reported to be an anti-tumor agent. However, its anti-tumor mechanism against hepatocellular carcinoma is unknown. This study aimed to explore the inhibitory effect of PGD in hepatocellular carcinoma cells and related mechanisms of action. We found that PGD exerted significant inhibitory effect on hepatocellular carcinoma cells through apoptosis and autophagy. Analysis of the expression of apoptosis-related proteins and autophagy-related proteins revealed that this phenomenon was attributed to the mitochondrial apoptosis and mitophagy pathways. Subsequently, using specific inhibitors, we found that apoptosis and autophagy had mutually reinforcing effects. In addition, further analysis of autophagy showed that PGD induced mitophagy by increasing BCL2 interacting protein 3 like (BNIP3L) levels.In vivo experiments demonstrated that PGD significantly inhibited tumor growth and increased the levels of apoptosis and autophagy in tumors. Overall, our findings showed that PGD induced cell death of hepatocellular carcinoma cells primarily through mitochondrial apoptosis and mitophagy pathways. Therefore, PGD can be used as an apoptosis and autophagy agonist in the research and development of antitumor agents.

N2 fixation in urbanization area rivers: spatial-temporal variations and influencing factors.

While nitrogen (N2) fixation is an important process in nitrogen (N) biogeochemical cycling, supplying a significant portion of the N in natural ecosystems, few quantitative constraints exist concerning its contribution to the N enrichment and export from river ecosystems. This study estimates the N2 fixation rates of urban rivers in the Yangtze Estuary area using acetylene reduction. The results demonstrate that the prominent spatiotemporal variability of river N2 fixation rates is driven by various environmental factors. River N2 fixation rates are significantly higher in the summer (90.57 ± 14.60 ngN·L-1·h-1) than in the winter (57.98 ± 15.73 ngN·L-1·h-1). Spatially, rivers draining urban and suburban areas have higher N2 fixation rates than those draining rural areas. The N2 fixation rates are positively correlated with the N2 fixing cyanobacteria density, water temperature, light, and the water phosphorus (P) concentration, but they are negatively correlated with the dissolved N concentration (NH4+-N and NO3--N). The N2 fixation rates annually range from 53.20 to 89.24 ngN·L-1·h-1 for all of the sampling rivers, which is equivalent to a depth integrated (0-0.6 m) N input of 0.163-0.274 gN·m-2·a-1. The determined annual N input via N2 fixation is generally higher than that of marine systems, but it is lower than that of eutrophic lakes. This study provides robust evidence that N2 fixation can supply a substantial portion of the N input to human-impacted river ecosystems, which has not been sufficiently accounted for when determining the N mass balance of riverine ecosystems. A high N2 fixation rate may increase the ratio of N to P input to river systems, and therefore render P the limiting factor in aquatic eutrophication.

Baicalein inhibits mitochondrial apoptosis induced by oxidative stress in cardiomyocytes by stabilizing MARCH5 expression.

Abnormal mitochondrial fission and mitophagy participate in the pathogenesis of many cardiovascular diseases. Baicalein is a key active component in the roots of traditional Chinese medicinal herb Scutellaria baicalensis Georgi. It has been reported that baicalein can resist cardiotoxicity induced by several stress, but the mechanisms of baicalein operate in the protection of cardiomyocytes need to be researched further. Here we report that baicalein can promote cell survival under oxidative stress by up-regulating the expression level of MARCH5 in cardiomyocytes. Pre-treatment cells or mice with baicalein can stabilize the expression of MARCH5, which plays a crucial role in the regulation of mitochondrial network and mitophagy. Overexpressed MARCH5 is able to against H2 O2 and ischaemia/reperfusion (I/R) stress by suppressing mitochondrial fission and enhancing mitophagy, and then attenuate cells apoptosis. Altogether, our present study investigated that baicalein exerts a protective effect through regulating KLF4-MARCH5-Drp1 pathway, our research also provided a novel theoretical basis for the clinical application of baicalein.

Phosphorus loads from different urban storm runoff sources in southern China: a case study in Wenzhou City.

Storm runoff from six types of underlying surface area during five rainfall events in two urban study areas of Wenzhou City, China was investigated to measure phosphorus (P) concentrations and discharge rates. The average event mean concentrations (EMCs) of total phosphorus (TP), total dissolved phosphorus (TDP), and particulate phosphorus (PP) ranged from 0.02 to 2.5 mg · L(-1), 0.01 to 0.48 mg · L(-1), and 0.02 to 2.43 mg · L(-1), respectively. PP was generally the dominant component of TP in storm runoff, while the major form of P varied over time, especially in roof runoff, where TDP made up the largest portion in the latter stages of runoff events. Both TP and PP concentrations were positively correlated with pH, total suspended solids (TSS), and biochemical oxygen demand (BOD)/chemical oxygen demand (COD) concentrations (p<0.01), while TDP was positively correlated with BOD/COD only (p<0.01). In addition, the EMCs of TP and PP were negatively correlated with maximum rainfall intensity (p<0.05), while the EMCs of TDP positively correlated with the antecedent dry weather period (p<0.05). The annual TP emission fluxes from the two study areas were 367.33 and 237.85 kg, respectively. Underlying surface type determined the TP and PP loadings in storm runoff, but regional environmental conditions affected the export of TDP more significantly. Our results indicate that the removal of particles from storm runoff could be an effective measure to attenuate P loadings to receiving water bodies.