Spatio-temporal patterns of zooplankton community in the Yellow River estuary: Effects of seasonal variability and water-sediment regulation.

Zooplankton community is ecological important because of its high sensitivity to environmental changes especially in estuarine areas. The Yellow River estuary (YRE) in China is the fifth biggest estuary in the world with significant seasonal characteristics and anthropogenic influence of Water-Sediment Regulation (WSR). This study investigated the spatio-temporal patterns of zooplankton in the YRE to explore the response of zooplankton to seasonal variation and WSR. Results suggested that the temporal patterns of zooplankton were mainly characterized by seasonal shift of dominant species. Hierarchical cluster analysis and non-metric multidimensional scaling determined summer, summer-autumn and winter-spring three zooplankton assemblages. Zooplankton spatial distributions represented seasonal consistency, in which the abundance generally showed a decreasing gradient from the river mouth to sea. WSR caused a high species replacement rate in July-August (80.36%) and a dramatic abundance decline from 4224.60 ind./m3 to 1541.10 ind./m3 with persistency and hysteresis effect. The high zooplankton abundance moved seaward in spatial distribution after WSR. Summer spatial pattern was determined with two and three zooplankton station assemblages, which was more clear after WSR. Redundancy analysis identified SSS, SST and transparency as important factors structuring zooplankton spatio-temporal patterns, in which SSS was the key one. The results provide a necessary reference for understanding the response of zooplankton community in estuarine areas to spontaneous changes and anthropogenic factors, and can help the protection of estuarine ecosystems and the formulation of hydrological regulatory policies.

25-hydroxyvitamin D3 inhibits oxidative stress and ferroptosis in retinal microvascular endothelial cells induced by high glucose through down-regulation of miR-93.

BACKGROUND: The decrease of vitamin D plays a critical role in diabetes mellitus (DM)-induced oxidative stress and vascular endothelial injury. Therefore, we investigated the effect and mechanism of 25-hydroxyvitamin D3 (25 (OH) D3) on oxidative stress and ferroptosis induced by high glucose in human retinal microvascular endothelial cells (hRMVECs). And the objective of this paper was to propose a new strategy for the prevention and treatment of diabetic retinopathy (DR). METHODS: First, hRMVECs were transfected with mimics NC or miR-93. After that, cells were treated with 100 nM / 500 nM 25 (OH) D3 and then cultured in a high glucose (30 mM) environment. Subsequently, qRT-PCR was employed to detect the expression level of miR-93; CCK-8 for the proliferation of cells in each group; biochemical tests for the level of intracellular reactive oxygen species (ROS), malondialdehyde (MDA), reduced glutathione (GSH) and ferrous ion (Fe2+); and Western blot for the expression of ferroptosis-related proteins glutathione peroxidase 4 (GPX4) and SLC7A11). RESULTS: Under a high glucose environment, 25 (OH) D3 at 100 nM/500 nM could significantly promote the proliferation of hRMVECs, remarkably decrease the level of intracellular ROS/MDA, and up-regulate the level of GSH. Besides, 25 (OH) D3 greatly reduced Fe2+ level in the cells while increased protein level of GPX4 and SLC7A11. Subsequently, we found that high glucose induced miR-93 expression, while 25 (OH) D3 markedly decreased high glucose-induced miR-93 overexpression. Furthermore, overexpression of miR-93 inhibited the functions of 25 (OH) D3 by activating ROS (ROS and MDA were up-regulated while GSH was down-regulated) and inducing Fe2+ (Fe2+ level was up-regulated while GPX4 and SLC7A11 level was down-regulated) in cells. CONCLUSION: 25 (OH) D3 may inhibit oxidative stress and ferroptosis in hRMVECs induced by high glucose via down-regulation of miR-93.

The Invention of WM382, a Highly Potent PMIX/X Dual Inhibitor toward the Treatment of Malaria.

Drug resistance to first-line antimalarials-including artemisinin-is increasing, resulting in a critical need for the discovery of new agents with novel mechanisms of action. In collaboration with the Walter and Eliza Hall Institute and with funding from the Wellcome Trust, a phenotypic screen of Merck's aspartyl protease inhibitor library identified a series of plasmepsin X (PMX) hits that were more potent than chloroquine. Inspired by a PMX homology model, efforts to optimize the potency resulted in the discovery of leads that, in addition to potently inhibiting PMX, also inhibit another essential aspartic protease, plasmepsin IX (PMIX). Further potency and pharmacokinetic profile optimization efforts culminated in the discovery of WM382, a very potent dual PMIX/X inhibitor with robust in vivo efficacy at multiple stages of the malaria parasite life cycle and an excellent resistance profile.

Celastrol Inhibits the Proliferation and Decreases Drug Resistance of Cisplatin- Resistant Gastric Cancer SGC7901/DDP Cells.

BACKGROUND: This study aimed to determine the effect and mechanism of Celastrol inhibiting the proliferation and decreasing the drug resistance of cisplatin-resistant gastric cancer cells. OBJECTIVE: The objective of this study was to explore the effect and mechanism of Celastrol on proliferation and drug resistance of human gastric cancer cisplatin-resistant cells SGC7901/DDP. METHODS: The thiazole blue (MTT) method was used to detect the sensitivity of human gastric cancer cisplatinresistant cells SGC7901/DPP to cisplatin and Celastrol to determine the Drug Resistance Index (DRI). According to the half Inhibitory Concentration (IC50) value, the action of the concentration of the following experimental drugs was set to reduce the cytotoxicity. Annexin V-FITC/PI double staining method was used to detect the apoptosis of SGC7901/DDP cells induced by Celastrol. Western Blot was used to examine the expression levels of P-glycoprotein (P-gp), Multidrug Resistance Associated Protein 1 (MRP1), Breast Cancer Resistance Associated Protein (Breast Cancer Resistance)-relative protein (BCRP), and mechanistic Target of Rapamycin (mTOR) pathway-related proteins. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression levels of P-gp, MRP1, and BCRP. RESULTS: (1) Compared with the control group (we set the untreated group as the control group), the proliferation of the SGC7901/DPP cells was significantly inhibited after treating with 0.1-6.4µmol/L Celastrol in a time- and concentration-dependent manner (P<0.05). The Drug Resistance Index (DRI) of the SGC7901/DPP cells to DDP was 5.64. (2) Compared with the control group, Celastrol could significantly inhibit the proliferation and induce the apoptosis of the SGC7901/DPP cells (P<0.05). (3) The mRNA and protein expression levels of P-gp, MRP1, and BCRP in the SGC7901/DPP cells were significantly higher than those in the SGC7901 cells. However, after treating with Celastrol, the expression levels of P-gp, MRP1, and BCRP in the SGC7901/DPP cells were significantly reduced (P<0.05). (4) Compared with the control group, the Celastrol treatment also reduced the expression of the mTOR signaling pathway-related proteins, suggesting that the mTOR signaling pathway may be involved in the process of Celastrol inhibiting the proliferation of the SGC7901/DDP cells and reducing their drug resistance. (5) Significantly, the combination of Celastrol and DDP reduced the expression of P-gp, MRP1, and BCRP in the SGC7901/DPP cells. CONCLUSION: Celastrol can inhibit the proliferation of the SGC7901/DDP cells, induce their apoptosis, and reduce the expression of drug resistance genes, probably by inhibiting the expression of the proteins related to the mTOR signaling pathway.

Habitat hierarchies distribution of Sargassum muticum in Lidao bay, Shandong, China based on habitat suitability index model.

We used the habitat suitability index (HSI) model to determine the habitat suitability of Sargassum muticum in Lidao bay, Shandong Province. Eight environmental factors, including temperature, salinity, depth, turbidity, sediment, inorganic nitrogen concentration, phosphate concentration, distance from seaweed bed, were used as input variables for HSI model. The weight of each factor was defined by the analytic hierarchy process (AHP). We implemented the distribution of S. muticum suitable habitat along the coast of Lidao bay with the HSI model, based on the investigation of the environmental factors in spring and autumn 2018. The results showed that most of the S. muticum natural habitats were identified as excellent habitat and suitable habitat, accounting for 14.2% in spring and 18.6% in autumn. The distribution of habitat hierarchies varied across seasons, while habitat hierarchies showed spatial intersections in different seasons. There were significant seasonal differences in the factor suitability indices of temperature and phosphate concentration, which accounted for the seasonal HSI variations of S. muticum in Lidao bay. The S. muticum HSI model could be used to detect the habitat hierarchies distribution of S. muticum, and also to find its potential suitable habitat, which could provide a reference for future resource conservation and artificial proliferation of S. muticum.

CD133+/CD166+ human gastric adenocarcinoma cells present the properties of neoplastic stem cells and emerge more malignant features.

AIMS: The recurrence and metastasis of gastric cancer has always been an important factor affecting the prognosis of gastric cancer. Cancer stem cells can promote the recurrence and growth of gastric cancer. The identification and isolation of gastric cancer stem cells contribute to the origin, progress and treatment strategy of gastric cancer. The aim of this study was to identify and isolate gastric cancer stem cells, and provide targets for the treatment of gastric cancer. METHODS: Magnetic-activated cell sorting was used to isolate CD133+/CD166+ cell populations from human gastric adenocarcinoma cell lines (BGC-823 and SGC-7901). Sphere formation, cell proliferation, resistance to chemotherapy, colony formation, migration invasion and tumorigenicity in vivo of these cell populations were evaluated. Moreover, RT-qPCR and Western blot were used to investigate the expression level of the stem cell markers Nanog, Sox2, Oct-4, and c-Myc. RESULTS: CD133+/CD166+ cell subpopulations presented more malignant features than CD133-/CD166-, CD133-/CD166+, CD133+/CD166- cell populations and parental cells. Moreover, the mRNA and protein expression level of Oct-4 and c-Myc were higher in CD133+/CD166+ cells than in parental cells or other cell populations. CONCLUSION: The CD133+/CD166+ populations of human gastric cancer cell lines BGC-823 and SGC-7901 have cancer stem cell characteristics.

Integrated Transcriptome, microRNA, and Phytochemical Analyses Reveal Roles of Phytohormone Signal Transduction and ABC Transporters in Flavor Formation of Oolong Tea (Camellia sinensis) during Solar Withering.

The unique aroma and flavor of oolong tea develop during the withering stage of postharvest processing. We explored the roles of miRNA-related regulatory networks during tea withering and their effects on oolong tea quality. We conducted transcriptome and miRNA analyses to identify differentially expressed (DE) miRNAs and target genes among fresh leaves, indoor-withered leaves, and solar-withered leaves. We identified 32 DE-miRNAs and 41 target genes involved in phytohormone signal transduction and ABC transporters. Further analyses indicated that these two pathways regulated the accumulation of flavor-related metabolites during tea withering. Flavonoid accumulation was correlated with the miR167d_1-ARF-GH3, miR845-ABCC1-3/ABCC2, miR166d-5p_1-ABCC1-2, and miR319c_3-PIF-ARF modules. Terpenoid content was correlated with the miR171b-3p_2-DELLA-MYC2 and miR166d-5p_1-ABCG2-MYC2 modules. These modules inhibited flavonoid biosynthesis and enhanced terpenoid biosynthesis in solar-withered leaves. Low auxin and gibberellic acid contents and circRNA-related regulatory networks also regulated the accumulation of flavor compounds in solar-withered leaves. Our analyses reveal how solar withering produces high-quality oolong tea.

Roles of tissue plasminogen activator and its inhibitor in proliferative diabetic retinopathy.

AIM: To investigate the role of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) in proliferative diabetic retinopathy (PDR) and to discuss the correlations among t-PA, PAI and vascular endothelial growth factor (VEGF) expressions. METHODS: A total of 36 vitreous samples were collected from 36 patients with PDR (PDR group), and 17 vitreous samples from 17 patients with idiopathic macular hole were used as control. The concentrations of t-PA, PAI and VEGF in samples were determined by ELISA method. The correlations among t-PA, PAI and VEGF expressions were discussed. RESULTS: The concentrations of t-PA, PAI and VEGF in the PDR group were significantly higher than those in the control group (P<0.001). The t-PA and PAI expressions were highly correlated with the VEGF expression (P<0.001). CONCLUSION: In addition to VEGF, a variety of bioactive substances, such as t-PA and PAI, are involved in the pathogenesis involved in the angiogenesis of PDR. VEGF can activate t-PA expression, resulting in collagen tissue degradation and angiogenesis. VEGF may also activate the mechanism for endogenous anti-neovascularization.

Synthesis and biological evaluation of quinazoline and quinoline bearing 2,2,6,6-tetramethylpiperidine-N-oxyl as potential epidermal growth factor receptor(EGFR) tyrosine kinase inhibitors and EPR bio-probe agents.

4-anilinoquinazoline and 4-anilinoquinoline scaffolds bearing a 2,2,6,6-tetramethylpiperidine-N-oxyl(TEMPO) have been synthesized and evaluated for their ability to inhibit EGFR tyrosine kinase and A431 cell lines. Compared to their corresponding parent compounds, all of the new compounds bearing a TEMPO showed more efficient inhibition for EGFR and A431 cells. Furthermore, we have proved that these molecules bearing a TEMPO can exactly get into A431 cells exerting inhibitory effect that may be used for EPR detecting. In our docking model, quinazolines bearing a TEMPO on either 6- or 3-positions took different linking modes according to EGFR crystal structure. In contrast to their parent compounds, these new TEMPO-derived analogues possessed compatible inhibitory effect that might be useful as potential EGFR inhibitors and as EPR bio-probes.