RESUMEN
Mouse embryonic stem cells (mESCs) sporadically transition to a transient totipotent state that resembles blastomeres of the two-cell (2C) embryo stage, which has been proposed to contribute to exceptional genomic stability, one of the key features of mESCs. However, the biological significance of the rare population of 2C-like cells (2CLCs) in ESC cultures remains to be tested. Here we generated an inducible reporter cell system for specific elimination of 2CLCs from the ESC cultures to disrupt the equilibrium between ESCs and 2CLCs. We show that removing 2CLCs from the ESC cultures leads to dramatic accumulation of DNA damage, genomic mutations, and rearrangements, indicating impaired genomic instability. Furthermore, 2CLCs removal results in increased apoptosis and reduced proliferation of mESCs in both serum/LIF and 2i/LIF culture conditions. Unexpectedly, p53 deficiency results in defective response to DNA damage, leading to early accumulation of DNA damage, micronuclei, indicative of genomic instability, cell apoptosis, and reduced self-renewal capacity of ESCs when devoid of 2CLCs in cultures. Together, our data reveal that transition to the privileged 2C-like state is a major component of the intrinsic mechanisms that maintain the exceptional genomic stability of mESCs for long-term self-renewal.
RESUMEN
BACKGROUND: The early detection of COVID-19 patients is fundamental for containing the pandemic. A reverse-transcriptase quantitative polymerase chain reaction (RT-PCR), which detects SARS-CoV-2 RNA, is the gold standard diagnostic test, although it can contribute to false-negative results. Consequently, supplementary diagnostic tests are urgently needed. METHODS: To assess the value of anti-SARS-CoV-2 antibody-based tests for confirming COVID-19, a retrospective study was conducted on 3120 inbound overseas travelers who underwent a 14-day government quarantine in Xiamen from August 2020 to October 2020. The diagnostic accuracy of the total antibody that detected the anti-SARS-CoV-2 antibody and the RT-PCR that detected SARS-CoV-2 RNA was determined in comparison to the clinical diagnosis. RESULTS: The COVID-19 positive rate was 3.14% (98/3120). The sensitivity and specificity of the RT-PCR test on the first day of quarantine were 14.29% and 100%, respectively, and the sensitivity and specificity of the total antibody were 93.88% and 99.40%, respectively. The kappa value between an RT-PCR on the first day of quarantine and a clinical diagnosis was 0.24 (95% CI, 0.14-0.35), indicating poor consistency. The kappa value between total antibodies and a clinical diagnosis was 0.88 (95% CI, 0.83-0.93), indicating perfect consistency. There were no differences in the positive rates of an RT-PCR in symptomatic COVID-19 (7.41% (2/27)) and asymptomatic COVID-19 (16.90 (12/71) (p = 0.338). Similarly, the positive rate of the total antibody tests showed no difference in symptomatic COVID-19 (96.30% (26/27)) and asymptomatic COVID-19 (92.96% (66/71)) (p = 0.676). CONCLUSION: SARS-CoV-2 antibodies are developed by the body in response to an infection or after vaccination; this can easily lead to a missed diagnosis. In the context of low sensitivity for an RT-PCR, SARS-CoV-2 antibody detection is an effective adjunct to RT-PCR detection, which can improve the diagnostic accuracy of COVID-19 and provide an effective complement to the false-negative results of an RT-PCR.
RESUMEN
The exposure risk of metal-based nanoparticles (NPs) to marine organisms and related food safety have attracted increasing attention, but the actual concentrations of these NPs in seawater and marine organisms are unknown. In this work, single particle inductively coupled plasma-mass spectrometry (spICP-MS) was used to quantify the concentrations and size distributions of NPs in different marine mollusks (oysters, mussels, scallops, clams, and ark shells) from an offshore aquaculture farm. Results showed that Ti, Cu, Zn, and Ag bearing NPs were detected in all the five mollusks with the mean sizes at 65.4-70.9, 72.2-89.6, 97.8-108.3, and 42.9-51.0 nm, respectively. The particle concentrations of Ti, Cu, Zn, and Ag bearing NPs in all mollusks (0.88-3.26 × 107 particles/g fresh weight) were much higher than that in the seawater (0.46-0.79 × 107 particles/mL), suggesting bio-accumulation of NPs. For all the five mollusks, Ag bearing NPs had the highest number-based bioconcentration factors (NBCFs) in all the tested NPs due to the smallest mean size of Ag bearing NPs in seawater (30.5 nm). In addition, the clams exhibited the lowest NBCFs of the four NPs than other mollusks. All four NPs were mainly accumulated in the gill and digestive gland, and could transfer to adductor muscle of all mollusks. Although all the four metals (Ti, Cu, Zn, Ag) in mollusks were safe for human consumption by the estimated daily intake (EDI) analysis, the risk of NPs remaining in the mollusks should be further considered when evaluating the toxicity of metals for human health. The findings could improve our understanding on the distribution and health risk of NPs in marine mollusks under offshore aquaculture.