Mechanism of the Synergistic Toxicity of Ampicillin and Cefazoline on Selenastrum capricornutum.

Ampicillin (AMP) and cefazolin (CZO) are commonly used ß-lactam antibiotics which are extensively globally produced. Additionally, AMP and CZO are known to have relatively high ecotoxicity. Notably, the mix of AMP and CZO creates a synergistic effect that is more harmful to the environment, and how exposure to AMP-CZO can induce synergism in algae remains virtually unknown. To yield comprehensive mechanistic insights into chemical toxicity, including dose-response relationships and variations in species sensitivity, the integration of multiple endpoints with de novo transcriptomics analyses were used in this study. We employed Selenastrum capricornutum to investigate its toxicological responses to AMP and CZO at various biological levels, with the aim of elucidating the underlying mechanisms. Our assessment of multiple endpoints revealed a significant growth inhibition in response to AMP at the relevant concentrations. This inhibition was associated with increased levels of reactive oxygen species (ROS) and perturbations in nitrogen metabolism, carbohydrate metabolism, and energy metabolism. Growth inhibition in the presence of CZO and the AMP-CZO combination was linked to reduced viability levels, elevated ROS production, decreased total soluble protein content, inhibited photosynthesis, and disruptions in the key signaling pathways related to starch and sucrose metabolism, ribosome function, amino acid biosynthesis, and the production of secondary metabolites. It was concluded from the physiological level that the synergistic effect of Chlorophyll a (Chla) and Superoxide dismutase (SOD) activity strengthened the growth inhibition of S. capricornutum in the AMP-CZO synergistic group. According to the results of transcriptomic analysis, the simultaneous down-regulation of LHCA4, LHCA1, LHCA5, and sodA destroyed the functions of the photosynthetic system and the antioxidant system, respectively. Such information is invaluable for environmental risk assessments. The results provided critical knowledge for a better understanding of the potential ecological impacts of these antibiotics on non-target organisms.

Toxicity interactions of azole fungicide mixtures on Chlorella pyrenoidosa.

It is acknowledged that azole fungicides may release into the environment and pose potential toxic risks. The combined toxicity interactions of azole fungicide mixtures, however, are still not fully understood. The combined toxicities and its toxic interactions of 225 binary mixtures and 126 multi-component mixtures on Chlorella pyrenoidosa were performed in this study. The results demonstrated that the negative logarithm 50% effect concentration (pEC50 ) of 10 azole fungicides to Chlorella pyrenoidosa at 96 h ranged from 4.23 (triadimefon) to 7.22 (ketoconazole), while the pEC50 values of the 351 mixtures ranged from 3.91 to 7.44. The high toxicities were found for the mixtures containing epoxiconazole. According to the results of the model deviation ratio (MDR) calculated from the concentration addition (MDRCA ), 243 out of 351 (69.23%) mixtures presented additive effect at the 10% effect, while the 23.08% and 7.69% of mixtures presented synergistic and antagonistic effects, respectively. At the 30% effect, 47.29%, 29.34%, and 23.36% of mixtures presented additive effects, synergism, and antagonism, respectively. At the 50% effect, 44.16%, 34.76%, and 21.08% of mixtures presented additive effects, synergism, and antagonism, respectively. Thus, the toxicity interactions at low concentration (10% effect) were dominated by additive effect (69.23%), whereas 55.84% of mixtures induced synergism and antagonism at high concentration (50% effect). Climbazole and imazalil were the most frequency of components presented in the additive mixtures. Epoxiconazole was the key component induced the synergistic effects, while clotrimazole was the key component in the antagonistic mixtures.

Role of BCL2L10 in regulating buffalo (Bubalus bubalis) oocyte maturation.

It has been reported that BCL2L10 is abundantly and specifically expressed in adult human and mouse oocytes and played a very important role in oocytes maturation and early embryonic development. This study is to investigate the expression pattern of BCL2L10 in buffalo ovaries and its effect on the in vitro maturation of buffalo oocytes, so as to dissect mechanism of oocytes maturation and provide theoretical guidance for improvement of the in vitro maturation of buffalo oocytes. The results showed that BCL2L10 gene was enriched in ovary and the expression of BCL2L10 was oocyte specific and up-regulated during oocyte maturation. BCL2L10 protein and mRNA were detectable in buffalo early embryos, upregulated at 2-cell to 8-cell stages and down-regulated in the later stages. Knockdown of BCL2L10 by RNA interference resulted in a significant decrease in the maturation rate (33.5%) and cleavage rate (37.52%) of buffalo oocytes coupled with up-regulation of apoptosis-related gene Caspase-9. We concluded that BCL2L10 is a candidate associated with buffalo oocyte maturation.

Spermatogenesis-associated proteins at different developmental stages of buffalo testicular seminiferous tubules identified by comparative proteomic analysis.

The testicular seminiferous tubules contain Sertoli cells and different types of spermatogenic cells. They provide the microenvironment for spermatogenesis, but the precise molecular mechanism of spermatogenesis is still not well known. Here, we have employed tandem mass tag coupled to LC-MS/MS with the high-throughput quantitative proteomics technology to explore the protein expression from buffalo testicular seminiferous tubules at three different developmental stages (prepuberty, puberty, and postpuberty). The results show 304 differentially expressed proteins with a ≥2-fold change, and bioinformatics analysis indicates that 27 of these may be associated with spermatogenesis. Expression patterns of seven selected proteins were verified via Western blot and quantitative RT-PCR analysis, and further cellular localizations of these proteins by immunohistochemical or immunofluorescence analysis. Taken together, the results provide potential molecular markers of spermatogenesis and provide a rich resource for further studies on male reproduction regulation.

[Applications and progress of Fourier transform infrared spectroscopic microimaging in bone disease research].

Fourier transform infrared spectroscopy (FTIRS) and microimaging technique have been integrated together to evolve into Fourier transform infrared spectroscopic imaging (FTIRI) system. This system can provide not only the morphological information of the sample by visible image and FTIR image, but also the abundant information on the spectral, component and structure of specimen by FTIRS, especially of the heterogeneous solid mixture. The richer and more visualized information obtained by FTIRI greatly raised the research efficiency and usability of the spectral technique in biomedicine, pharmacology, forensic medicine, material science and chemistry, etc. The present paper depicts FTIRI development process, system structure, imaging principle and mode selection; and then introduces that FTIRI opened a new area of investigation for biomedicine, namely, research on bone disease by FTIRI. Then the paper illustrates the related research findings and progress in FTIRI use for osteopetrosis, osteogenesis imperfecta, osteoporosis and osteomalacia, as well as a couple of limitations. The prospective study for FTIRI in biomedical research field is also addressed.

[Comparison of antitumor efficacy between arsacetyl and arsenic trioxide in vitro].

BACKGROUND & OBJECTIVE: Recently, it was reported that some organic arsenics was stronger than inorganic arsenics in inducing carcinoma cell apoptosis. This study was designed to compare arsacetyl (ASAC), a kind of organic arsenics, with As2O3 in the effect of inhibiting proliferation and inducing apoptosis in carcinoma cells. METHODS: MTT (Methythiazolyl tetrazolium) assay and analysis of apoptosis were used to evaluate the effects of arsacetyl and As2O3 on the proliferation of SMMC-7721 and their mechanisms. Their toxicity to vessel endothelium cells (VECs) was also determined by using MTT method. RESULTS: Both As2O3 and arsacetyl significantly inhibited the proliferation of SMMC-7721, the inhibitory effect was dose- and time-dependent and arsacetyl was stronger than As2O3 [e.g. inhibitory ratio: (14.2 +/- 1.5)%, treated with 0.1 mumol/L arsacetyl for 48 h; (27.1 +/- 3.0)%, treated with 0.1 mumol/L arsacetyl for 48 h]. 1 mumol/L As2O3 and 0.1 mumol/L arsacetyl almost had no toxicity to VEC, while they induced SMMC-7721 apoptosis indicated morphologically by "small apoptopic body" formation; DNA ladders appeared on agarose gel electrophoresis. The flow cytometry assay indicated that most of the cells were arrested in S + G2/M phase and the apoptotic peak appeared. CONCLUSION: The ability of arsacetyl inducing apoptosis was stronger than As2O3, and SMMC-7721 in the G0/G1 phase may be the target of drug action.

[Protective effect of magnesium on hippocampal neurons damage induced by glutamic acid].

AIM: To investigate the effect of magnesium ion (Mg2+) on neuronic damage induced by 0.1 mmol/L glutamic acid. METHODS: The neurons isolated from hippocampus in rats were cultured for 6-9 days, and then randomly divided into three groups: A. medium alone. B. medium + glutamic acid. C. medium+ Mg2+, and + glutamic acid (30 min late). RESULTS: (1) DAs compared with A group, the survival rate of hippocampal neurons in B group was remarkably decreased in dose dependent mauner. (2) In contrast to B group, when the concentration of Mg2+ was lower, the survival rates of hippocampal neurons in C group was significantly increased. CONCLUSION: Mg2+ in lower concentration could protect hippocampal neurons from damage induced by glutamic acid.