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The nucleosome remodeling and deacetylase (NuRD) complex is essential for gene expression and cell fate determination, and missense mutations of NuRD caused neurodevelopmental diseases. However, the molecular pathogenesis of clinic NuRD variants is unknown. Here, we introduced a clinic CHD3 (L915F) variant into Caenorhabditis eleganshomologue LET-418, impairing germline and vulva development and ultimately causing animal sterility. Our ATAC-seq and RNA-seq analyses revealed that this variant generated an abnormal open chromatin structure and disrupted the expression of developmental genes. Through genetic suppressor screens, we uncovered that intragenic mutations, likely renovating NuRD activity, restored animal viability. We also found that intergenic mutations in nucleosome remodeling factor NURF that counteracts NuRD rescued abnormal chromatin structure, gene expression, and animal sterility. We propose that two antagonistic chromatin-remodeling factors coordinate to establish the proper chromatin status and transcriptome and that inhibiting NURF may provide insights for treatment of NuRD mutation-related diseases.

In this paper, the stressing state modeling analysis of the residual strain data of H-steel columns reveals three characteristic points that exist during the failure of H-steel columns. Also, the correctness of the stressing state analysis method, residual, and buckling characteristic pairs was verified. First, the experimental residual strains were transformed into generalized strain energy density (GSED) values as the state variables for establishing the stressing state mode and characteristic parameters (characteristic pairs). The Mann-Kendall (M-K) criterion is applied to the normalized GSED sum-jcurves to reveal the characteristic points P, Q, and U of the evolving stressing state of the H-steel column. Characteristic point P is defined as the elastic-plastic branch point of the H-steel column, characteristic point Q is defined as the failure starting point, and characteristic point U is defined as the progressive failure point. Around the characteristic points of the H-steel columns, the directly modeled stressing state characteristic pairs, residual characteristic pairs, and buckling characteristic pairs produce significant mutation characteristics. This phenomenon verifies the correctness of the revealed H-steel column characteristic points and the rationality of this paper's stressing state modeling method. Then, it is proposed that the elastic-plastic branch point P can be directly used as the design reference point, and it is compared with the design point given by Code EN1993–1–5. In conclusion, this paper provides new ideas for analyzing steel structures and opens up the value of residual strain data in structural analysis.

This paper presents a stressing state modeling analysis of pavement strain data from phase I of the Federal Aviation Administration (FAA) construction cycle 8 (CC8). The objective is to reveal the operating characteristics and accurately determine the characteristic points of the stressing states of concrete pavements in the south and north halves under normal and overload. This study proposes a correlation stressing state modeling method to model the pavement strain data by converting the test strain data into basic, composite, and reconstructed state variables and establishing correlation characteristic pair (mode-characteristic parameter) to describe the interconnection between the measurement points. Then, the slope increment criterion is applied to the characteristic parameter curves to screen the characteristic points of concrete airport pavements and verify their mutation characteristics in the vicinity of the correlation mode and characteristic parameter curves. The characteristic points P and F were defined as the elastoplastic branching (EPB) points and the failure starting points, where the characteristic points of the overall stressing state in the north and south halves of the concrete airport pavement were (jP=55, jF=98) and (jP=38, jF=54), respectively. Furthermore, this study suggests that the characteristic points P and F are used as references for pavement design.

In response to the current coronavirus disease 2019 (COVID-19) pandemic, it is crucial to understand the origin, transmission, and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which relies on close surveillance of genomic diversity in clinical samples. Although the mutation at the population level had been extensively investigated, how the mutations evolve at the individual level is largely unknown. Eighteen time-series fecal samples were collected from nine patients with COVID-19 during the convalescent phase. The nucleic acids of SARS-CoV-2 were enriched by the hybrid capture method. First, we demonstrated the outstanding performance of the hybrid capture method in detecting intra-host variants. We identified 229 intra-host variants at 182 sites in 18 fecal samples. Among them, nineteen variants presented frequency changes >0.3 within 1–5 days, reflecting highly dynamic intra-host viral populations. Moreover, the evolution of the viral genome demonstrated that the virus was probably viable in the gastrointestinal tract during the convalescent period. Meanwhile, we also found that the same mutation showed a distinct pattern of frequency changes in different individuals, indicating a strong random drift. In summary, dramatic changes of the SARS-CoV-2 genome were detected in fecal samples during the convalescent period; whether the viral load in feces is sufficient to establish an infection warranted further investigation.