Integration of transcriptomics and metabolomics analysis for unveiling the toxicological profile in the liver of mice exposed to uranium in drinking water.

Uranium is a contaminate in the underground water in many regions of the world, which poses health risks to the local populations through drinking water. Although the health hazards of natural uranium have been concerned for decades, the controversies about its detrimental effects continue at present since it is still unclear how uranium interacts with molecular regulatory networks to generate toxicity. Here, we integrate transcriptomic and metabolomic methods to unveil the molecular mechanism of lipid metabolism disorder induced by uranium. Following exposure to uranium in drinking water for twenty-eight days, aberrant lipid metabolism and lipogenesis were found in the liver, accompanied with aggravated lipid peroxidation and an increase in dead cells. Multi-omics analysis reveals that uranium can promote the biosynthesis of unsaturated fatty acids through dysregulating the metabolism of arachidonic acid (AA), linoleic acid, and glycerophospholipid. Most notably, the disordered metabolism of polyunsaturated fatty acids (PUFAs) like AA may contribute to lipid peroxidation induced by uranium, which in turn triggers ferroptosis in hepatocytes. Our findings highlight disorder of lipid metabolism as an essential toxicological mechanism of uranium in the liver, offering insight into the health risks of uranium in drinking water.

Single-cell profiling reveals differences between human classical adenocarcinoma and mucinous adenocarcinoma.

Colorectal cancer is a highly heterogeneous disease. Most colorectal cancers are classical adenocarcinoma, and mucinous adenocarcinoma is a unique histological subtype that is known to respond poorly to chemoradiotherapy. The difference in prognosis between mucinous adenocarcinoma and classical adenocarcinoma is controversial. Here, to gain insight into the differences between classical adenocarcinoma and mucinous adenocarcinoma, we analyse 7 surgical tumour samples from 4 classical adenocarcinoma and 3 mucinous adenocarcinoma patients by single-cell RNA sequencing. Our results indicate that mucinous adenocarcinoma cancer cells have goblet cell-like properties, and express high levels of goblet cell markers (REG4, SPINK4, FCGBP and MUC2) compared to classical adenocarcinoma cancer cells. TFF3 is essential for the transcriptional regulation of these molecules, and may cooperate with RPS4X to eventually lead to the mucinous adenocarcinoma mucus phenotype. The observed molecular characteristics may be critical in the specific biological behavior of mucinous adenocarcinoma.

PAH residue and consumption risk assessment in four commonly consumed wild marine fishes from Zhoushan Archipelago, East China Sea.

The concentration, constitution, distribution, possible sources, and associated consumption risks of polycyclic aromatic hydrocarbons (PAHs) in four marine fishes in the Zhoushan Archipelago were investigated. The concentrations of PAHs in the edible muscle of these four fishes ranged from 34.7 to 108 ng/g wet weight. Four-ring and six-ring PAH congeners constitute the most and least percentages of the total PAHs, respectively. The highest PAH concentrations were found in Mugil cephalus, followed by Sebastiscus marmoratus, Lateolabrax maculatus, and Collichthys lucidus. The highest PAH concentrations were found at the sampling island Liuheng, followed by Gouqi, Qushan, Dongji, and Zhujiajian. PAH concentrations in wet weight were remarkably different among these four fish species but not among different locations. High-molecular-weight congeners predominated the PAH composition pattern in most of the samples. Results showed that the consumption of M. cephalus might have potential carcinogenic risk. This study provided baseline data on PAH concentrations in seafood and consequent human consumption risk.

Large-scale sequencing of flatfish genomes provides insights into the polyphyletic origin of their specialized body plan.

The evolutionary and genetic origins of the specialized body plan of flatfish are largely unclear. We analyzed the genomes of 11 flatfish species representing 9 of the 14 Pleuronectiforme families and conclude that Pleuronectoidei and Psettodoidei do not form a monophyletic group, suggesting independent origins from different percoid ancestors. Genomic and transcriptomic data indicate that genes related to WNT and retinoic acid pathways, hampered musculature and reduced lipids might have functioned in the evolution of the specialized body plan of Pleuronectoidei. Evolution of Psettodoidei involved similar but not identical genes. Our work provides valuable resources and insights for understanding the genetic origins of the unusual body plan of flatfishes.

Development of Human Lung Induction Models for Air Pollutants' Toxicity Assessment.

There is an urgent need for reliable and effective models to study air pollution health effects on human lungs. Here, we report the utilization of human pluripotent stem cell (hPSC) induction models for human lung progenitor cells (hLPs) and alveolar type 2 epithelial cell-like cells (ATLs) for the toxicity assessment of benzo(a)pyrene, nano-carbon black, and nano-SiO2, as common air pollutants. We induced hPSCs to generate ATLs, which recapitulated key features of human lung type 2 alveolar epithelial cells, and tested the induction models for cellular uptake of nanoparticles and toxicity evaluations. Our findings reveal internalization of nano-carbon black, dose-dependent uptake of nano-SiO2, and interference with surfactant secretion in ATLs exposed to benzo(a)pyrene/nano-SiO2. Thus, hLP and ATL induction models could facilitate the evaluation of environmental pollutants potentially affecting the lungs. In conclusion, this is one of the first studies that managed to adopt hPSC pulmonary induction models in toxicology studies.

Antiviral nanoagents: More attention and effort needed?

The recent COVID-19 outbreak has increasingly engaged researchers in the search for effective antiviral drugs as well as therapeutic treatment options. The shortcomings of existing antiviral agents such as narrow spectrum and low bioavailability, can be overcome through the use of engineered nanomaterials, which, therefore, are considered as a significant next-generation therapeutic option. Thus, the development of novel antiviral nanoagents will certainly help address several future challenges and knowledge gaps.

Elevated non-essential metals and the disordered metabolism of essential metals are associated to abnormal pregnancy with spontaneous abortion.

Spontaneous abortion is a considerable threat to the physiology and mental health of the mother. The etiology of spontaneous abortion is multifactorial with complicated mechanisms, of which overexposure to non-essential metals (especially heavy metals) has been proposed to be associated with adverse birth outcomes. However, significant knowledge gaps remain to be filled in, such as the deleterious profile of non-essential metals and their interplay with essential metals in abnormal pregnancy. Under this setting, we aimed to address these challenges by conducting a cross-sectional study on 56 patients with spontaneous abortion in the 1st trimester, by comparing to 55 healthy pregnant women in 1st the trimester and 41 non-pregnant healthy women. Overexposure to a few non-essential metals, such as arsenic (As), antimony (Sb) and bismuth (Bi), was found in patients with spontaneous abortion, and likewise, some essential elements, such as magnesium (Mg), copper (Cu), vanadium (V), strontium (Sr) and tin (Sn), were also found to be elevated under spontaneous abortion. Further evidence of abnormal pregnancy was induced by a reduced level of internal hormones necessary for normal gestation, such as estradiol (E2) and progesterone (PRGE) in women with spontaneous abortion. Lactate dehydrogenase (LDH) and thyroid-stimulating hormone (TSH) levels were slightly increased in patients with spontaneous abortion. Comprehensive correlation analyses were carried out to identify the crucial factors that result in abortion. Our data stratified the important variables in decreasing order: PRGE, As, Mg, Sb, Sr, Sn, Bi and pregnant times in the progress of spontaneous abortion. Moreover, labyrinthine associations were uncovered between PRGE, non-essential metals and essential elements in causing spontaneous abortion. Therefore, our combined data unveiled the likely synergistic implications of elevated non-essential metals and the disordered metabolism of essential metals in abnormal pregnancy.

Low-dose PCB126 compromises circadian rhythms associated with disordered glucose and lipid metabolism in mice.

It has been documented that 3, 3', 4, 4', 5-pentachlorobiphenyl (PCB126) elicits diverse detrimental effects on human health including metabolic syndrome and non-alcoholic fatty-liver disease (NAFLD), through a wide array of non-carcinogenic mechanisms, which require further detailed investigations. The circadian clock system consists of central clock machinery (located in the suprachiasmatic nucleus in the hypothalamus) and the peripheral clocks (located in nearly all peripheral tissues). Peripheral clocks in the liver play fundamental roles in maintaining liver homeostasis, including the regulation of energy metabolism and the expression of enzymes that fine-tune the absorption and metabolism of xenobiotics. However, the molecular basis of whether PCB126 disrupts liver homeostasis (e.g., glucose and lipid metabolism) by dysregulating the circadian clock system is still unknown. Thus, we performed a set of comprehensive analyses of glucose and lipid metabolism in the liver tissues from low-dose PCB126-treated mice. Our results demonstrated that PCB126 diminished glucose and cholesterol levels in serum and elevated glucose and cholesterol levels in the liver. Moreover, PCB126 compromised PGC1α and PDHE1α, which are the driving force for mitochondrial biogenesis and entry of pyruvate into the tricarboxylic acid (TCA) cycle, respectively, and resulted in the accumulation of glucose, glycogen and pyruvate in the liver after PCB126 exposure. Additionally, PCB126 blocked hepatic cholesterol metabolism and export pathways, leading to an elevated localization of hepatic cholesterol. Mechanistic investigations illustrated that PCB126 greatly altered the expression profile of core clock genes and their target rhythm genes involved in orchestrating glucose and cholesterol metabolism. Together, our results demonstrated that a close correlation between PCB126-disturbed glucose and lipid metabolism and disordered physiological oscillation of circadian genes.

Diagnostic significance of metallothionein members in recognizing cadmium exposure in various organs under low-dose exposure.

Metallothioneins (MTs) are known to protect cells against oxidative stress, especially providing protection against cadmium (Cd) toxicity. To date, besides liver and kidney, the expression profiles of MT members have not been thoroughly determined in a full-spectrum of organs, especially under low-dose exposure settings. Furthermore, their diagnostic value has not been evaluated in reflecting the Cd exposure in diverse organs. In the present study, we unearthed the expression profiles of five MT members in diverse organs from mice upon low-dose Cd exposure. Compared to most organs, the deposition of Cd in cartilage has been overlooked in the past, implying the potential Cd toxicity to the joint. In contrast to MT1 and MT2 (MT1/2), the expression levels of MT3, MTL5 and MT4 were minimal with or without Cd treatment. Distinct from Cd mass, the levels of MT1/2 were similar in heart and lung to that of kidney. Our study signified the rationale of MT1/2 induction in recognizing Cd exposure extent in diverse organs including liver, kidney, heart and lung. Importantly, MT1/2 expression was induced in liver and lung cells even upon low-dose Cd exposure. Thus, our combined data unraveled the expression of MT members across various organs in Cd-exposed mice, and pinpointed their diagnostic value in characterizing Cd poisoning.

PAHs and PCBs residues and consumption risk assessment in farmed yellow croaker (Larimichthys crocea) from the East China Sea, China.

Large yellow croaker (Larimichthys crocea) purchased from five different farming sites in Zhoushan Archipelago and Xiangshan Harbor in the East China Sea, China were analyzed for polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs). Concentrations of PAHs and PCBs in the edible muscle of L. crocea ranged from 83.14 to 174.68 ng/g wet weight (or 266.89 to 695.24 ng/g dry weight) and 3.89 to 17.40 ng/g wet weight (or 15.50 to 54.25 ng/g dry weight), respectively. Incremental lifetime cancer risk (ILCR) associated with the dietary intake of PAHs and PCBs in L. crocea was assessed. Results showed that levels of PAHs in L. crocea were high enough to cause potential carcinogenic risks for human consumption, while, levels of PCBs in fish samples were of low significant carcinogenic risk.

Silver Nanoparticles Compromise Female Embryonic Stem Cell Differentiation through Disturbing X Chromosome Inactivation.

The widespread use of silver nanoparticles (AgNPs) has raised substantial health risks to human beings. Despite a wealth of progress on toxicity studies, the understanding of the adverse effects on fetuses, embryos, and early stage cells is still rather limited, particularly under low-dose exposure settings. Moreover, nearly all previous studies ascribed AgNP-induced toxic effects to oxidative stress. Differently, we here unearthed a mechanism, namely, interruption of X chromosome inactivation (XCI) in female mouse embryonic stem cells (mESCs). Albeit with no observable cytotoxicity, significant differentiation retardation was found in female mESCs upon low-dose AgNP exposure. Mechanistic investigations uncovered expedited inactivation for the inactive X chromosome (Xi) and attenuated maintenance of the active X chromosome (Xa) state during mESC differentiation upon the challenge of low-dose AgNPs, indicative of disordered XCI. Thereby, a few X-linked genes (which are closely involved in orchestrating ESC differentiation) were found to be repressed, partially attributable to reinforced enrichment of histone modification ( e. g., histone 3 lysine 27 trimethylation, H3K27me3) on their promoter regions, as the result of disordered XCI. In stark contrast to female mESCs, no impairment of differentiation was observed in male mESCs under low-dose AgNP exposure. All considered, our data unearthed that AgNPs at low concentrations compromised the differentiation program of female mESCs through disturbing XCI. Thus, this work would provide a model for the type of studies necessary to advance the understandings on AgNP-induced developmental toxicity.

Chromosomal level reference genome of Tachypleus tridentatus provides insights into evolution and adaptation of horseshoe crabs.

Horseshoe crabs including Tachypleus tridentatus are a group of marine arthropods and living fossil species which have existed on the earth for ~500 million years. However, the genetic mechanisms underlying their unique adaptive ability are still unclear. Here, we assembled the first chromosome-level T. tridentatus genome, and proved that this genome is of high quality with contig N50 1.69 Mb. By comparison with other arthropods, some gene families of T. tridentatus experienced significant expansion, which are related to several signaling pathways, endonuclease activities, and metabolic processes. Based on the results of comparative analysis of genomics and 27 transcriptomes from nine tissues, we found that the expanded Dscam genes are located at key hub positions of immune network. Furthermore, the Dscam genes showed higher levels of expression in the yellow connective tissue (the birthplace of blood cells with strong differentiation capability) than the other eight tissues. Besides, the Dscam genes are positively correlated with the expression of the core immunity gene, clotting factor B, which is involved in the coagulation cascade reaction. The effective and unusual immune ability endowed by the expansion and expression of Dscam genes in the horseshoe crab may be a factor that makes the species have a strong environmental adaptability within ~500 million years. The high quality chromosome level genome of a horseshoe crab and unique genomic features reported in this study provide important data resources for future studies on the evolution of marine ecological systems.

Two-Dimensional Nanomaterials for Cancer Nanotheranostics.

Emerging nanotechnologies show unprecedented advantages in accelerating cancer theranostics. Among them, two-dimensional nanomaterials (2DNMs) represent a novel type of material with versatile physicochemical properties that have enabled a new horizon for applications in both cancer diagnosis and therapy. Studies have demonstrated that 2DNMs may be used in diverse aspects, including i) cancer detection due to their high propensity towards tumor markers; ii) molecular imaging for guided tumor therapies, and iii) drug and gene loading, photothermal and photodynamic cancer therapies. However, their biomedical applications raise concerns due to the limited understanding of their in vivo metabolism, transformation and possible toxicities. In this comprehensive review, the state-of-the-art development of 2DNMs and their implications for cancer nanotheranostics are presented. The modification strategies to enhance the biocompatibility of 2DNMs are also reviewed.

Complete mitochondrial genome of the needle cuttlefish Sepia aculeata (Sepioidea, Sepiidae).

In this study, we determined the complete mitochondrial genome of the needle cuttlefish Sepia aculeata. The genome was 16,219 bp in length and contained 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and 2 main non-coding regions [both are control regions (CR)]. The composition and order of genes, for the mitogenome found in S. aculeate, were similar to most other invertebrates. The overall base composition of S. aculeata is T 34.0%, C 17.0%, A 40.5% and G 8.5%, with a highly A + T bias of 74.5%. Two control regions (CR) both contain termination-associated sequences and conserved sequence blocks. This mitogenome sequence data would play an important role in the investigation of phylogenetic relationship, taxonomic resolution and phylogeography of the Sepiidae.

[Research on the identification of penis et testis cervi with molecular taxonomy].

OBJECTIVE: To make the kit with witch to identify Penis et Testis Cervi with molecular taxonomy. METHOD: The mtDNA of sika and red deer from different areas was amplified by PCR and sequenced. Compared with the mtDNA of bovine and horse from witch the false medicines were made, characteristic segments of deer were found. We selected one as the species distinctive PCR primer of deer. RESULT: The kit made up with this primer and related reagents could be used to discern Penis et Testis Cervi from the false medicine. CONCLUSION: It is a scientific, steady, accurate and convenient way to identify Penis et Testis Cervi with molecular taxonomy.

Characterization of Sarcocystis species in domestic animals using a PCR-RFLP analysis of variation in the 18S rRNA gene: a cost-effective and simple technique for routine species identification.

Thirteen restriction endonucleases were used to investigate nuclotide sequence variation in the 18S rRNA DNA of 88 individuals from ten Sarcocystis taxa collected as cysts from their intermediate hosts, swine, cattle and water buffalo. A DNA sequence of approximately 900 bp was used. A total of 26 electromorphs were detected. The electromorphs were sorted into seven different haplotypes that coincided with the six named species and an unidentified species from cattle. These findings support those of our morphological examinations, which suggested that the taxa resembling Sarcocystis hirsuta, S. hominis, both found in water buffalo, and S. sinensis found in cattle, are not new species but are in fact S. hirsuta and S. hominis as found in cattle, and S. sinensis as found in water buffalo; this finding supports the idea that these species can utilize both cattle and water buffalo as intermediate hosts and are not restricted to one or the other host group as previously thought. PCR-RFLP resolved by agarose gel electrophoresis is shown to be an easy and rapid method of discriminating between these species.