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Emerging evidence suggests a link between alterations in the gut microbiome and adverse health outcomes in the hosts exposed to environmental pollutants. Yet, the causal relationships and underlying mechanisms remain largely undefined. Here we show that exposure to biotoxins can affect gut pathobiome assembly in amphibians, which in turn triggers the toxicity of exogenous pollutants. We used Xenopus laevis as a model in this study. Tadpoles exposed to tropolone demonstrated notable developmental impairments and increased locomotor activity, with a reduction in total length by 4.37%–22.48% and an increase in swimming speed by 49.96%–84.83%. Fusobacterium and Cetobacterium are predominant taxa in the gut pathobiome of tropolone-exposed tadpoles. The tropolone-induced developmental and behavioral disorders in the host were mediated by assembly of the gut pathobiome, leading to transcriptome reprogramming. This study not only advances our understanding of the intricate interactions between environmental pollutants, the gut pathobiome, and host health but also emphasizes the potential of the gut pathobiome in mediating the toxicological effects of environmental contaminants.

Porcine circovirus-associated diseases, caused by porcine circovirus type 2 (PCV2), are widespread and result in significant economic losses to the global swine industry. PCV2 can currently be divided into nine genotypes (PCV2a to PCV2i), with the currently dominant one being the PCV2d genotype. In this study, 2675 samples from 804 pig farms in 13 cities in Jiangsu Province, China, were collected between 2014 and 2021 and subjected to polymerase chain reaction analysis to investigate the frequency and genetic diversity of PCV2. The results showed that 41.42% (1108/2675) of samples tested positive for PCV2. The researchers further analyzed the genetic characteristics of 251 PCV2 strains and found that they belonged to the following four genotypes: PCV2a, PCV2b, PCV2d, and PCV2i. The dominant genotype was PCV2d, with a frequency of 49.80% (125/251). The detection rate of PCV2b was significantly higher than those of PCV2a and PCV2i, at 35.46% (89/251), 7.57% (19/251), and 7.17% (18/251), respectively. The percentage of different genotypes of PCV2 varied irregularly over time. We have further revealed the fingerprint of PCV2i genomic nucleotides for the first time. In conclusion, this study illustrates the high frequency and evolutionary features of PCV2 in Jiangsu Province over the past few years.

Abstract Porcine circovirus‐like virus P1, like porcine circovirus type 2 (PCV2), is a potential pathogen of post‐weaning multisystemic wasting syndrome in swine. Yaks are a valuable species and an iconic symbol of the Tibet Plateau which is the highest and largest plateau in the world. In this study, a total of 105 yak diarrheal samples, collected from 13 farms in Linzhi in the Tibet Plateau from January 2019 to December 2021, that were screened for P1 and PCV2 by polymerase chain reaction, 10.48% (n = 11) were positive for P1, 4.76% (n = 5) for PCV2, and 5.71% (n = 6) were positive for coinfection of P1 and PCV2. In addition, the whole genomes of eight P1 strains and eight PCV2 strains were sequenced. Alignment of deduced amino acid sequences of P1 ORF1 and PCV2 ORF2 gene revealed that ON012566 had one unique amino acid mutation at residues 137 (T to P). This mutation has important implication for the study of virus virulence, tissue tropism, and immune response. Phylogenetic analysis shows that the yak‐origin P1 strains in this study with cattle‐origin P1 reference strains were grouped into one cluster. The yak‐origin PCV2 (ON012566) and a buffalo‐origin PCV2 (KM116514) reference strain clustered in the same branch in the PCV2b regions. Meanwhile, the remaining PCV2 strains and buffalo‐origin PCV2 reference strain (ON012565) clustered in the PCV2d regions. To summarize, to our knowledge, this is the first report on the molecular prevalence and genome characteristics of P1 and PCV2 in yaks in the world and will contribute to further study of the molecular epidemiology, source, and evolution of P1 and PCV2 strains.

Decabromodiphenyl ethane (DBDPE), a widely used novel brominated flame retardant, is gaining concerns due to rapidly increased contents in various environmental and biota samples. In the present study, zebrafish (Danio rerio) embryos were exposed to 2.91, 9.71, 29.14 and 97.12 μg/L of DBDPE until 120 h post-fertilization (hpf) to investigate the potential developmental neurotoxicity and underlying mechanisms. Chemical analysis revealed concentration-dependently increased body burdens of DBDPE in zebrafish larvae, with bioaccumulation factors (BCFs) ranging from 414 to 726. Embryonic exposure to DBDPE caused hyperactivity without affecting the development of secondary motoneuron axons and muscle fibers. However, further results implicated that DBDPE may affect the locomotor regulatory network via different mechanisms at lower and higher concentrations. On the one hand, embryonic exposure to 2.91 μg/L DBDPE transiently promoted spontaneous coiling contractions, but showed no effects on touch-response and swimming activity in zebrafish larvae. The whole-body contents of neurotransmitters were significantly decreased. Significant decreased protein abundances of α1-TUBULIN and SYN2a and molecular docking results pointed out possible interactions of DBDPE with these two proteins. However, these changes may be unconcerned with the transient hyperactivity, and the exact molecular mechanisms need further investigation. On the other hand, 29.14 and 97.12 μg/L DBDPE exposure caused longer-lasting effects in promoting spontaneous coiling contractions, and also touch-response and swimming activity. At the same time, increased ACh contents (without changes of other neurotransmitters) and ChAT activity and inhibited transcription of nAChRs were observed at higher concentrations. Molecular docking indicated direct interaction of DBDPE with ChAT. The results suggested that DBDPE induced hyperactivity at higher concentrations was probably involved with disrupted cholinergic system, with ChAT as a potential target. Given that the body burden of DBDPE in lower concentration group was comparable with those detected in wild fish, the current results may provide useful information for ecological risk assessment.

A growing body of evidence has demonstrated the significance of the gut microbiota in host health, while the association between gut microbiota dysbiosis and multiple diseases is yet elusive in the scenario of exposure to widely used pesticides. Here, we show that gut microbiota dysbiosis involves in host's abnormal lipid metabolism and consequently the non-alcoholic fatty liver disease in Xenopus laevis upon exposure to cis-bifenthrin, one of the most prevalent pyrethroid insecticides in the world. With the guidance of gut microbiota analysis, we found that cis-bifenthrin exposure significantly perturbed the gut microbial community, and the specific taxa that served as biomarkers were identified. Metabolomics profiling and association analysis further showed that a significant change of intestinal metabolites involved in lipid metabolic pathways were induced along with the microbiota dysbiosis upon exposure to cis-bifenthrin. Detailed investigation showed an altered functional regulation of lipids in the liver after cis-bifenthrin exposure and the accumulation of lipid droplets in hepatocytes. Specifically, a change in deoxycholic acid alters bile acid hepatoenteral circulation, which affects lipid metabolism in the liver and ultimately causes the development of fatty liver disease. Collectively, these findings provide novel insight into the gut microbiota dysbiosis upon pesticide exposure and their potential implication in the development of chronic host diseases related to liver metabolic syndrome.

Abstract Background Porcine circovirus-like virus P1 is a relatively new kind of virus that is closely related to the post-weaning multisystemic wasting syndrome, congenital tremors, and abortions in swine. The molecular mechanisms of P1 virus infection and pathogenesis are fully unknown. To analyze P1 and its host interactions, we used a yeast two-hybrid (Y2H) assay to identify cellular proteins interacting with the Cap of the P1 virus. In this study, the Cap of the P1 virus exhibited no self-activation and toxicity to yeast cells and was used as bait to screen the Y2H library prepared from the pancreas tissue. Results Five cellular proteins (EEP, Ral GDS, Bcl-2-L-12, CPS1, and one not identified) were found to interact with P1 Cap. The interaction between Cap and Ral GDS was confirmed by co-immunoprecipitation. Conclusions Our data are likely to support the future investigation of the underlying mechanism of P1 infection and pathogenesis.

Porcine circovirus-like virus P1 can infect many kinds of animals and mainly causes postweaning multisystemic wasting syndrome. In China, the genetic diversity, variation, and evolutionary processes of this virus have not been described yet. To improve our knowledge of its genetic diversity, evolution, and gene flow, we performed a bioinformatics analysis using the available nucleotide sequences of the P1 virus; among them, 12 nucleotide sequences were from ten pig farms in Jiangsu Province in this epidemiological survey, and 84 sequences were downloaded from GenBank. The P1 sequences showed a rich composition of AT nucleotides. Analyses of the complete genomic sequences were polymorphic and revealed high haplotype (gene) diversity and nucleotide diversity. A phylogenetic analysis based on the NJ method showed that all P1 virus sequences formed two distinct groups: A and B. High genetic differentiation was observed between strains from groups A and B. The codon usage pattern of P1 was affected by dinucleotide compositions. Dinucleotide UU/CC was overrepresented, and dinucleotide CG was underrepresented. The mean evolutionary rate of the P1 virus was estimated to be 3.64 × 10−4 nucleotide substitutions per site per year (subs/site/year). The neutrality tests showed negative values. The purifying selection and recombination events may play a major driving role in generating the genetic diversity of the P1 population. The information from this research may be helpful to obtain new insights into the evolution of P1.

C14H10N10O2, monoclinic, P21/n (no. 14), a = 9.6366(19) Å, b = 9.5098(19) Å, c = 16.095(3) Å, β = 103.59(3)°, V = 1433.7(5) Å3, Z = 4, Rgt(F) = 0.0579, wRref(F2) = 0.1309, T = 153(2) K.

C26H16CuN12O2, monoclinic, C2/c (no. 15), a = 18.800(4) Å, b = 21.224(4) Å, c = 14.436(3) Å, β = 112.094(6)°, V = 5337.1(18) Å3, Z = 8, Rgt(F) = 0.0468, wRref(F2) = 0.1287, T = 296(2) K.

Retinal ganglion cells (RGCs) are the sole output neurons conveying visual stimuli from the retina to the brain, and dysfunction or loss of RGCs is the primary determinant of visual loss in traumatic and degenerative ocular conditions. Currently, there is a lack of RGC-specific Cre mouse lines that serve as invaluable tools for manipulating genes in RGCs and studying the genetic basis of RGC diseases. The RNA-binding protein with multiple splicing (RBPMS) is identified as the specific marker of all RGCs. Here, we report the generation and characterization of a knock-in mouse line in which a P2A-CreERT2 coding sequence is fused in-frame to the C-terminus of endogenous RBPMS, allowing for the co-expression of RBPMS and CreERT2. The inducible Rbpms-CreERT2 mice exhibited a high recombination efficiency in activating the expression of the tdTomato reporter gene in nearly all adult RGCs as well as in differentiated RGCs starting at E13.5. Additionally, both heterozygous and homozygous Rbpms-CreERT2 knock-in mice showed no detectable defect in the retinal structure, visual function, and transcriptome. Together, these results demonstrated that the Rbpms-CreERT2 knock-in mouse can serve as a powerful and highly desired genetic tool for lineage tracing, genetic manipulation, retinal physiology study, and ocular disease modeling in RGCs.

Abstract  It is well known that mathematical programs with equilibrium constraints (MPEC) violate the standard constraint qualifications such as Mangasarian–Fromovitz constraint qualification (MFCQ) and hence the usual Karush–Kuhn–Tucker conditions cannot be used as stationary conditions unless relatively strong assumptions are satisfied. This observation has led to a number of weaker stationary conditions, with Mordukhovich stationary (M-stationary) condition being the strongest among the weaker conditions. In nonlinear programming, it is known that MFCQ leads to an exact penalization. In this paper we show that MPEC GMFCQ, an MPEC variant of MFCQ, leads to a partial exact penalty where all the constraints except a simple linear complementarity constraint are moved to the objective function. The partial exact penalty function, however, is nonsmooth. By smoothing the partial exact penalty function, we design an algorithm which is shown to be globally convergent to an M-stationary point under an extended version of the MPEC GMFCQ. [ABSTRACT FROM AUTHOR]

C14H10N10O2, monoclinic, P21/n (no. 14), a = 9.6366(19) Å, b = 9.5098(19) Å, c = 16.095(3) Å, β = 103.59(3)°, V = 1433.7(5) Å3, Z = 4, Rgt(F) = 0.0579, wRref(F2) = 0.1309, T = 153(2) K. [ABSTRACT FROM AUTHOR]

C26H16CuN12O2, monoclinic, C2/c (no. 15), a = 18.800(4) Å, b = 21.224(4) Å, c = 14.436(3) Å, β = 112.094(6)°, V = 5337.1(18) Å3, Z = 8, Rgt(F) = 0.0468, wRref(F2) = 0.1287, T = 296(2) K. [ABSTRACT FROM AUTHOR]

C26H16CuN12O2, monoclinic, C2/c (no. 15), a = 18.800(4) Å, b = 21.224(4) Å, c = 14.436(3) Å, β = 112.094(6)°, V = 5337.1(18) Å3, Z = 8, Rgt(F) = 0.0468, wRref(F2) = 0.1287, T = 296(2) K. [ABSTRACT FROM AUTHOR]

C14H10N10O2, monoclinic, P21/n (no. 14), a = 9.6366(19) Å, b = 9.5098(19) Å, c = 16.095(3) Å, β = 103.59(3)°, V = 1433.7(5) Å3, Z = 4, Rgt(F) = 0.0579, wRref(F2) = 0.1309, T = 153(2) K. [ABSTRACT FROM AUTHOR]

C4H10BaN8O6, triclinic, P1 (No. 2), a=7.6249(18) Å, b=7.8460(16) Å, c=11.723(3) Å, α=70.520(8)°, β=85.079(10)°, =64.007(7)°, V=592.792 ų, Z=2, Rgt(F)=0.0332, wRref(F²)=0.0734, T=153 K. [ABSTRACT FROM AUTHOR]

C6H6N12O16 . 0.33 H2O, orthorhombic, Pbca (no. 61), a=9.5152(7) Å, b=13.2551(11) Å, c=23.6736(18) Å, V=2985.8(7) ų, Z=4, Rgt(F)=0.0727, wRref(F²)=0.1268, T=293(2) K. [ABSTRACT FROM AUTHOR]

C4H7N8NaO4, monoclinic, C2/c (no. 15), a = 19.42(2) Å, b = 6.514(5) Å, c = 15.38(1) Å, β = 93.23(2)°, V = 1942.9 Ų, Z = 8, Rgt(F) = 0.0631, wRref(F²) = 0.1660, T = 293 K. [ABSTRACT FROM AUTHOR]

C4H7N8NaO4, monoclinic, C2/c (no. 15), a = 19.42(2) Å, b = 6.514(5) Å, c = 15.38(1) Å, β = 93.23(2)°, V = 1942.9 Ų, Z = 8, Rgt(F) = 0.0631, wRref(F²) = 0.1660, T = 293 K. [ABSTRACT FROM AUTHOR]

C6H6N12O16 . 0.33 H2O, orthorhombic, Pbca (no. 61), a=9.5152(7) Å, b=13.2551(11) Å, c=23.6736(18) Å, V=2985.8(7) ų, Z=4, Rgt(F)=0.0727, wRref(F²)=0.1268, T=293(2) K. [ABSTRACT FROM AUTHOR]