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.

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.

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.

High-quality solidification microstructure during directional solidification relies on precise temperature gradient control, so accurate calculation of the temperature field is critical. In this study, a 3D transient global heat transfer model of directional solidification by the Bridgman method based on the finite difference method is developed. The radiation heat in this model is calculated by the discrete transfer method, and a modified method of external surface area for irregular geometric models is proposed to reduce the zigzag shape caused by finite difference grids. Considering the radiative heat transfer between any surface elements of all materials in the directional solidification furnace, a dynamic ray tracing algorithm is developed to simulate the entire process of directional solidification. Then, the simulated results are compared with the theoretical results and experimental results, respectively. Finally, based on the present model and method, the simulation program developed is applied to the directional solidification of actual castings. The simulated results are in good agreement with the experimental results, which indicate that the model and method developed in this study is effective and practical.

Casting microstructure evolution is difficult to describe quantitatively by only a separate simulation of dendrite scale or grain scale, and the numerical simulation of these two scales is difficult to render compatible. A three-dimensional cellular automaton model couplling both dendritic scale and grain scale is developed to simulate the microstructure evolution of the nickel-based single crystal superalloy DD406. Besides, a macro–mesoscopic/microscopic coupling solution algorithm is proposed to improve computational efficiency. The simulation results of dendrite growth and grain growth of the alloy are obtained and compared with the results given in previous reports. The results show that the primary dendritic arm spacing and secondary dendritic arm spacing of the dendritic growth are consistent with the theoretical and experimental results. The mesoscopic grain simulation can be used to obtain results similar to those of microscopic dendrites simulation. It is indicated that the developed model is feasible and effective.