Rhodium-Catalyzed Direct Bis-cyanation of Arylimidazo[1,2-α]pyridine via Double C-H Activation.

An efficient Cp*Rh(III)-catalyzed selective bis-cyanation of arylimidazo[1,2-α]pyridines with N-cyano-N-phenyl-p-methylbenzenesulfonamide via N-directed ortho double C-H activation has been developed. The reaction proceeds with broad functional group tolerance to furnish various cyanated imidazopyridines in high yields. The current methodology exhibits unique characteristics, including high bis-cyanation selectivity, operational convenience, and gram-scale production.

Toxicogenomic assessment of hydroxylated metabolites of PBDEs on cetaceans: An in vitro study.

Despite their ban, polybrominated diphenyl ethers (PBDEs) are frequently detected in various environmental compartments including marine and coastal ecosystems due to their persistence, bio-accumulative, high production volumes, and widespread use. One of the major concerns from PBDEs is the transformation products, such as hydroxylated polybrominated diphenyl ethers (OH-BDEs), which are more bioactive than the parent compounds. For example, 6-hydroxy-2,2',4',4-tetrabromodiphenyl ether (6-OH-BDE-47) is a typical metabolite of PBDEs and cause endocrine system disruption, developmental toxicity, and neurotoxicity in different species. Despite being widely detected in marine environments, investigations on the toxicological mechanisms of 6-OH-BDE-47 in cetaceans remain scarce. High concentrations of PBDEs accumulate in cetaceans due to the long lifespan and large fat reserve. The accumulated PBDEs have become the major source of OH-BDEs in cetaceans. We exposed immortalized fibroblast cell lines from the skin of pygmy killer whales (PKW-LWHT) and Indo-Pacific finless porpoises (FP-LWHT) to 6-OH-BDE-47 and analyzed changes in cellular function using transcriptomic data, along with enzymatic activity. Exposure to the body-relevant body burdens of 6-OH-BDE-47 (250 and 500 ng mL-1) significantly decreased cell viability. Differentially expressed genes in FP-LWHT exposed to 6-OH-BDE-47 were primarily enriched in the pathways associated with steroid metabolism. Total cholesterol was decreased by 6-OH-BDE-47, whereas low-density lipoprotein cholesterol and triglyceride levels were significantly increased in FP-LWHT cells. In contrast, glycolysis was the main enriched function of differentially expressed genes in PKW-LWHT cells exposed to 6-OH-BDE-47, and the enzyme activity of phosphofructokinase and hexokinase was upregulated. Thus, even though the cell viability of both cell lines from these two species was significantly suppressed by 6-OH-BDE-47, the cellular response or affected cellular function was different between the Pygmy killer whale and the Indo-Pacific Finless Porpoise, suggesting a diverse response towards OH-BDEs exposure.

Interspecies differences in mammalian susceptibility to legacy POPs and trace metals using skin fibroblast cells.

The susceptibility to trace metals and legacy POPs is different between terrestrial and marine mammals. In this study, we established the first cell line from Indo-Pacific finless porpoises and compared the cellular responses of skin fibroblast cells from Pygmy killer whales, Pantropic spotted dolphins, Indo-Pacific finless porpoises, mice, and humans following exposure to copper, methylmercury, cadmium, PCB126, PCB153, and BDE47 to better understand the interspecies sensitivities of mammals to chemical pollutants. We conducted a risk assessment by comparing no-observed effect concentrations (NOEC), lowest-observed effect concentrations (LOEC), and half maximal effective concentrations (EC50) from cell viability assays and previously reported pollutant body burdens in mammals. Based on the in vitro data, Indo-Pacific finless porpoises were more sensitive to copper and methylmercury than other mammals. PCB153 exposure reduced cell viability in all mammals except humans, while PCB126 was more potent, with 13.33 µg/mL exposure reducing cell viability in all mammals. In contrast, BDE47 exposure reduced cell viability only in terrestrial mammals in addition to pantropic spotted dolphin. Based on the in vitro data and the natural context of metal concentrations, both methylmercury and cadmium posed a higher risk to cetaceans than human, while copper posed a lower risk to cetaceans. All three legacy POPs (PCB126, PCB153, and BDE47) posed minor risk to cetaceans for short-term exposure. This study demonstrated that a species-specific in vitro model may provide more accurate information on the potential risk of pollutants to mammals. However, due to the bioamplification of POPs and their potential impact on the endocrine system and immune system of cetaceans, risk assessment with long-term exposure with more in vitro models should be further studied.

Insights on Gut and Skin Wound Microbiome in Stranded Indo-Pacific Finless Porpoise (Neophocaena phocaenoides).

The gut microbiome is a unique marker for cetaceans' health status, and the microbiome composition of their skin wounds can indicate a potential infection from their habitat. Our study provides the first comparative analysis of the microbial communities from gut regions and skin wounds of an individual Indo-Pacific finless porpoise (Neophocaena phocaenoides). Microbial richness increased from the foregut to the hindgut with variation in the composition of microbes. Fusobacteria (67.51% ± 5.10%), Firmicutes (22.00% ± 2.60%), and Proteobacteria (10.47% ± 5.49%) were the dominant phyla in the gastrointestinal tract, while Proteobacteria (76.11% ± 0.54%), Firmicutes (22.00% ± 2.60%), and Bacteroidetes (10.13% ± 0.49%) were the dominant phyla in the skin wounds. The genera Photobacterium, Actinobacillus, Vibrio, Erysipelothrix, Tenacibaculum, and Psychrobacter, considered potential pathogens for mammals, were identified in the gut and skin wounds of the stranded Indo-Pacific finless porpoise. A comparison of the gut microbiome in the Indo-Pacific finless porpoise and other cetaceans revealed a possible species-specific gut microbiome in the Indo-Pacific finless porpoise. There was a significant difference between the skin wound microbiomes in terrestrial and marine mammals, probably due to habitat-specific differences. Our results show potential species specificity in the microbiome structure and a potential threat posed by environmental pathogens to cetaceans.