Treatment options for metastatic castrate-resistant prostate cancer (mCRPC) are limited and typically are centered on docetaxel-based chemotherapy. We previously reported that elevated miR-375 levels were significantly associated with poor overall survival of mCRPC patients. In this study, we evaluated if miR-375 induced chemo-resistance to docetaxel through regulating target genes associated with drug resistance. We first compared miR-375 expression level between prostate cancer tissues and normal prostate tissues using data from The Cancer Genome Atlas (TCGA). To examine the role of miR-375 in docetaxel resistance, we transfected miR-375 using a pre-miRNA lentiviral vector and examined the effects of exogenously overexpressed miR-375 on cell growth in two prostate cancer cell lines, DU145 and PC-3. To determine the effect of overexpressed miR-375 on tumor growth and chemo-resistance in vivo, we injected prostate cancer cells overexpressing miR-375 into nude mice subcutaneously and evaluated tumor growth rate during docetaxel treatment. Lastly, we utilized qRT-PCR and Western blot assay to examine two miR-375 target genes, SEC23A and YAP1, for their expression changes after miR-375 transfection. By examining 495 tumor tissues and 52 normal tissues from TCGA data, we found that compared to normal prostate, miR-375 was significantly overexpressed in prostate cancer tissues (8.45-fold increase, p value = 1.98E-23). Docetaxel treatment induced higher expression of miR-375 with 5.83- and 3.02-fold increases in DU145 and PC-3 cells, respectively. Interestingly, miR-375 appeared to play a dual role in prostate cancer proliferation. While miR-375 overexpression caused cell growth inhibition and cell apoptosis, elevated miR-375 also significantly reduced cell sensitivity to docetaxel treatment in vitro, as evidenced by decreased apoptotic cells. In vivo xenograft mouse study showed that tumors with increased miR-375 expression were more tolerant to docetaxel treatment, demonstrated by greater tumor weight and less apoptotic cells in miR-375 transfected group when compared to empty vector control group. In addition, we examined expression levels of the two miR-375 target genes (SEC23A and YAP1) and observed significant reduction in the expression at both protein and mRNA levels in miR-375 transfected prostate cancer cell lines. TCGA dataset analysis further confirmed the negative correlations between miR-375 and the two target genes (r = −0.62 and −0.56 for SEC23A and YAP1, respectively; p < 0.0001). miR-375 is involved in development of chemo-resistance to docetaxel through regulating SEC23A and YAP1 expression. Our results suggest that miR-375 or its target genes, SEC23A or YAP1, might serve as potential predictive biomarkers to docetaxel-based chemotherapy and/or therapeutic targets to overcome chemo-resistance in mCRPC stage.

Dibutyl phthalate (DBP) poses a severe threat to aquatic ecosystems, introducing hazards to both aquatic species and human health. The ecotoxic effects of DBP on aquatic organisms have not been fully investigated. This study investigates acute toxicity, oxidative damage, and antioxidant enzyme parameters in neonate and adultDaphnia magnaexposed to DBP. The obtained results show comparable DBP toxic responses in neonates and adults. The median lethal concentrations (LC₅₀) of DBP in neonates exposed for 24 and 48 h were 3.48 and 2.83 mg/L, respectively. The LC₅₀of adults for the same DBP exposure durations were 4.92 and 4.31 mg/L, respectively. Increased hydrogen peroxide and malondialdehyde were found in neonates and adults at both 24 and 48 h, while the total antioxidant capacity decreased. Superoxide dismutase activity increased significantly in neonates and adults exposed to 0.5 mg/L DBP, and subsequently diminished at higher DBP concentrations and prolonged exposure. Catalase and glutathione S-transferases activities both decreased markedly in neonates and adults. The changes observed were found to be time and concentration dependent. Overall, these data indicated that the acute toxic effects of DBP exposure on neonates were more pronounced than in adults, and oxidative injury may be the main mechanism of DBP toxicity. These results provide a functional link for lipid peroxidation, antioxidant capacity, and antioxidant enzyme levels in theDaphnia magnaresponse to DBP exposure.

Salt stress is one of the most serious abiotic factors that inhibit plant growth. Dunaliella salina has been recognized as a model organism for stress response research due to its high capacity to tolerate extreme salt stress. A proteomic approach based on isobaric tags for relative and absolute quantitation (iTRAQ) was used to analyze the proteome of D. salina during early response to salt stress and identify the differentially abundant proteins (DAPs). A total of 141 DAPs were identified in salt-treated samples, including 75 upregulated and 66 downregulated DAPs after 3 and 24 h of salt stress. DAPs were annotated and classified into gene ontology functional groups. The Kyoto Encyclopedia of Genes and Genomes pathway analysis linked DAPs to tricarboxylic acid cycle, photosynthesis and oxidative phosphorylation. Using search tool for the retrieval of interacting genes (STRING) software, regulatory protein–protein interaction (PPI) networks of the DAPs containing 33 and 52 nodes were built at each time point, which showed that photosynthesis and ATP synthesis were crucial for the modulation of early salinity-responsive pathways. The corresponding transcript levels of five DAPs were quantified by quantitative real-time polymerase chain reaction (qRT-PCR). These results presented an overview of the systematic molecular response to salt stress. This study revealed a complex regulatory mechanism of early salt tolerance in D. salina and potentially contributes to developing strategies to improve stress resilience.

The Manila clam Ruditapes philippinarum is one of the most important commercial bivalve species consumed in China. Evaluated metal burden in bivalve molluscs can pose potential risks to public health as a result of their frequent consumption. In this study, concentrations of 10 trace elements (Cu, Zn, Mn, Se, Ni, Cd, Cr, Pb, Hg and As) were determined in samples of the bivalve Ruditapes philippinarum, collected from nine mariculture zones along the coast of China between November and December in 2010, in order to evaluate the status of elemental metal pollution in these areas. Also, a public health risk assessment was untaken to assess the potential risks associated with the consumption of clams. The ranges of concentrations found for Cu, Zn, Mn, Se, Ni, Cd, Cr, Pb, Hg and As in R. philippinarum were 12.1–38.0, 49.5–168.3, 42.0–68.0, 4.19–8.71, 4.76–14.32, 0.41–1.11, 0.94–4.74, 0.32–2.59, 0.03–0.23 and 0.46–11.95 mg·kg⁻¹ dry weight, respectively. Clear spatial variations were found for Cu, Zn, Cr, Pb, Hg and As, whereas Mn, Se, Ni, and Cd did not show significant spatial variation. Hotspots of trace element contamination in R. philippinarum can be found along the coast of China, from the north to the south, especially in the Bohai and Yellow Seas. Based on a 58.1 kg individual consuming 29 g of bivalve molluscs per day, the values of the estimated daily intake (EDI) of trace elements analyzed were significantly lower than the values of the accepted daily intake (ADI) established by Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives (JFAO/WHO) and the guidelines of the reference does (RfD) established by the United States Environmental Protection Agency (USEPA). Additionally, the risk of trace elements to humans through R. philippinarum consumption was also assessed. The calculated hazard quotients (HQ) of all trace elements were less than 1. Consequently, there was no obvious public risk from the intake of these trace elements through R. philippinarum consumption.

As cement manufacturing accounts for 8% of global CO₂ emissions, there is an urgent need to tackle the environmental impacts of cement production and address the decarbonization of construction materials. Adopting supplementary cementitious materials (SCMs), including fly ash, slag, silica fume, etc., can be used as a partial replacement for ordinary Portland cement (OPC) to reduce CO₂ emissions related to the OPC industry, while providing benefits for waste valorization. This study aims to explore the sustainable utilization of a waste oyster shell powder (OSP)–lithium slag (LS)–ground granulated blast furnace slag (GGBFS) ternary SCM system in green concrete. The effect of OSP fineness on compressive strength, hydration products, pore structure, and transport properties in ternary SCM-based mortars was studied using a wide array of experimental techniques, including thermogravimetric analysis (TGA), scanning electron microscopy (SEM) analysis, Mercury intrusion porosimetry (MIP), the water absorption test and the rapid chloride penetration test (RCPT). The results revealed that the concrete with the ternary SCMs showed equivalent compressive strength compared to reference specimens. The water absorption and chloride ion charge of the RCPT in the concrete containing the ternary SCMs decreased by up to 30% and 81.4%, respectively. It was observed that the specimens incorporating the OSP with a mesh size of 3000 exhibited the highest compressive strength and the most refined microstructure.