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Background: Preterm premature rupture of membranes (PPROM) contributes to over one-third of preterm births, and PPROM infants are more susceptible to infections. However, the risk factors remain poorly understood. We here aim to investigate the association of duration of premature rupture of membranes (PROM) and environmental microbiota with the gut microbiota and infection in PPROM infants. Methods: Forty-six premature infants were recruited from two hospitals, and infant fecal and environmental samples were collected. 16 s rRNA sequencing was performed to analyze the fecal and environmental microbiome. Human inflammatory cytokines in cord vein plasma were measured. Results: The gut microbiota composition of PPROM infants was different from that of non-PPROM infants, and the microbiome phenotypes were predicted to be associated with a higher risk of infection, further evidenced by the significantly increased levels of IL-6 and IL-8 in cord vein plasma of PPROM infants. The diversity of the gut microbiota in PPROM infants increased significantly as the duration of PROM excessed 12 h, and Pseudomonas contributed significantly to the dynamic changes. The Pseudomonas species in the gut of PPROM infants were highly homologous to those detected in the ward environment, suggesting that prolonged PROM is associated with horizontal transmission of environmental pathogens, leading to a higher risk of infection. Conclusions: This study highlights that the duration of PROM is associated with the accumulation of environmental pathogens in the gut of PPROM infants, which is a risk factor for nosocomial infections. Improving environmental hygiene could be effective in optimizing the clinical care of PPROM infants.

When shield TBM tunnelling in abrasive sandy ground, the rational design of cutter parameters is critical to reduce tool wear and improve tunnelling efficiency. However, the influence mechanism of cutter parameters on scraper wear remains unclear due to the lack of a reliable test method. Geometry and material optimisation are often based on subjective experience, which is unfavourable for improving scraper geological adaptability. In the present study, the newly developed WHU-SAT soil abrasion test was used to evaluate the variation in scraper wear with cutter geometry, material and hardness. The influence mechanism of cutter parameters on scraper wear has been revealed according to the scratch characteristics of the scraper surface. Cutter geometry and material parameters have been optimised to reduce scraper wear. The results indicate that the variation in scraper wear with cutter geometry is related to the cutting resistance, frictional resistance and stress distribution. An appropriate increase in the front angle (or back angle) reduces the cutting resistance (or frictional resistance), while an excessive increase in the front angle (or back angle) reduces the edge angle and causes stress concentration. The optimal front angle, back angle and edge angle for quartz sand samples are α = 25°, β = 10° and γ = 55°, respectively. The wear resistance of the modelled scrapers made of different metal materials is related to the chemical elements and microstructure. The wear resistances of the modelled scrapers made of 45#, 06Cr19Ni10, 42CrMo4 and 40CrNiMoA are 0.569, 0.661, 0.691 and 0.728 times those made of WC-Co, respectively. When the alloy hardness is less than 47 HRC (or greater than 58 HRC), scraper wear decreases slowly with increasing alloy hardness as the scratch depth of the particle asperity on the metal surface stabilizes at a high (or low) level. However, when the alloy hardness is between 47 HRC and 58 HRC, scraper wear decreases rapidly with increasing alloy hardness as the scratch depth transitions from high to low levels. The sensitive hardness interval and recommended hardness interval for quartz sand are [47, 58] and [58, 62], respectively. The present study provides a reference for optimising scraper parameters and improving cutterhead adaptability in abrasive sandy ground tunnelling.

The development of CRISPR/Cas9-mediated base editors (BEs) provided a versatile tool for precise genome editing. The recently developed xCas9-derived base editors (xBEs) that recognize the NG PAM substantially expand the targeting scope in the genome, while their editing efficiency needs to be improved. Here, we described an improved version of xBEs by fusing the BPNLS and Gam to the N terminus of xBEs (BPNLS-Gam-xBE3 and BPNLS-xABE), and this version of base editor displayed higher targeting efficiency for the majority of detected sites. By using this improved version of xBEs, we successfully created and corrected pathogenic mutations at genomic sites with the NGN protospacer-adjacent motif in human cells. Lastly, we used BPNLS-Gam-xBE3 to model pathogenic mutations in discarded human tripronuclear (3PN) zygotes, and no obvious off-targets and indels were detected. Taken together, the data in our study offer an efficient tool for precise genome editing and, thus, an enriched base editing toolkit. Keywords: CRISPR/Cas, base editor, xCas9, base editing efficiency, pathogenic mutation, Wilson disease