Zhao Guo

Klebsiella pneumoniae is an important gram-negative opportunistic pathogen that causes a variety of infectious diseases, including urinary tract infections, bacteremia, pneumonia, and liver abscesses. With the emergence of multidrug-resistant (MDR) and hypervirulent K. pneumoniae (hvKP) strains, the rapid spread of these clinical strains in geography is particularly worrying. However, the detailed mechanisms of virulence and antibiotic resistance in K. pneumoniae are still not very clear. Therefore, studying and elucidating the pathogenic mechanisms and drug resistance mechanism of K. pneumoniae infection are important parts of current medical research. In this paper, we systematically summarized the virulence, biofilm, and antibiotic tolerance mechanisms of K. pneumoniae, and explored the application of whole genome sequencing and global proteomics, which will provide new clues for clinical treatment of K. pneumoniae.

The mesoscopic grain model is a multiscale model which takes into account both the dendrite growth mechanism and the vast numerical computation of the actual castings. Due to the pursuit of efficient computation, the mesoscopic grain calculation accuracy is lower than that of dendrite growth model. Improving the accuracy of mesoscopic grain model is a problem to be solved urgently. In this study, referring to the calculation method of solid fraction in microscopic dendrite growth model, a cellular automata model of 3D mesoscopic grain evolution for solid fraction calculated quantitatively at the scale of cell is developed. The developed model and algorithm validation for grain growth simulation is made by comparing the numerical results with the benchmark experimental data and the analytical predictions. The results show that the 3D grain envelopes simulated by the developed model and algorithm are coincident with the shape predicted by the analytical model to a certain extent. Then, the developed model is applied to the numerical simulation of solidification process of nickel-based superalloys, including equiaxed and columnar dendritic grain growth. Our results show good agreement with the related literature.

Histone ubiquitination regulates sperm formation and is important for nucleosome removal during spermatogenesis. RNF8 is an E3 ubiquitin ligase, and RAD6B is an E2 ubiquitin-conjugating enzyme. Both proteins participate in DNA damage repair processes via histone ubiquitination. Loss of RNF8 or RAD6B can lead to sterility in male mice. However, the specific mechanisms regulating these ubiquitin-mediated processes are unclear. In this study, we found that RNF8 knockout mice were either subfertile or sterile based on the numbers of offspring they produced. We explored the mechanism by which RAD6B and RNF8 knockouts cause infertility in male mice and compared the effects of their loss on spermatogenesis. Our results demonstrate that RAD6B can polyubiquitinate histones H2 A and H2B. In addition, RNF8 was shown to monoubiquitinate histones H2 A and H2B. Furthermore, we observed that absence of histone ubiquitination was not the only reason for infertility. Senescence played a role in intensifying male sterility by affecting the number of germ cells during spermatogenesis. In summary, both histone ubiquitination and senescence play important roles in spermatogenesis.