0.05),and it shows that IL-4 does not play a major role in the occurrence of CAP.There is correlation between the serum level of IL-4 and the occurrence of CAP(r=0.48,P

ObjectiveTo elucidate the association of immune response to hepatitis B vaccination with HLA-DRB1 * 12 allele as well as the level of IL-4 and IFN-γ.MethodsSeventy-four healthy college students from Guangxi province who had non- or hypor -response to recombinant hepatitis B vaccination and 64 medium- or hyper-responders with the conditions of similar were selected randomly and involved in this study.HLA-DRB1 * 12 was detected by PCR-SSP,the level of IFN-γ and IL-4 cytokines were examined by ELISA.Results(1)The allelic frequencies of HLA-DRB1 * 12 was lower in the non- or hypor-responders than that in the medium- or hyper-responders ( 10.8％ vs 32.8％,P=0.002) ; (2)The expression level of IFN-γ in the non- or hypor-responders ( 7.21±7.92 ) ng/ml was much less than that of the medium- or hyper- responders ( 16.36± 11.00) ng/ml ( P=0.000).(3) The expression level of IL-4 in the non- or hyporresponders (3.18±4.45) ng/ml was much less than that of the medium- or hyper- responders (7.76±5.71 ) ng/ml(P=0.000).(4)No significant differences was seen between the expression level of IFN-γ in the HLA-DRB1 * 12 positive ( 13.18± 11.24) ng/ml and the negative ( 11.00± 10.29 ) ng/ml ( P =0.349 ).(5)No significant differences was seen between the expression level of IL-4 in the HLA-DRB1 * 12 positive (5.947±4.530) ng/ml and the negative (5.132±5.800) ng/ml (P=0.423).ConclusionHLA-DRB1 * 12 might be the allele enhanced immune response to hepatitis B vaccination.The expression levels of IFN-γand IL-4 correlating to Thl/Th2 cells might affect on the immune response to hepatitis B vaccination.

Objective:To conduct a multidimensional quantification and analysis of the development trajectory of both "quality" and "quantity" in China's higher education from 2001 to 2021, and lay a solid foundation for the construction of a high-quality education system.Methods:Based on macro statistical data on education in China from 2001 to 2021, a comprehensive indicator system for the development level of higher education was established. This system included six dimensions: educational conditions, financial support, institutional safeguards, scientific research, social services, and international collaboration. Methods such as entropy-weighted TOPSIS, general difference index, spatial autocorrelation, and hot spot analysis were used to evaluate the level of high-quality development of higher education and its spatial differentiation. Additionally, an obstacle degree analysis model was used to evaluate the factors hindering the high-quality development of higher education.Results:The high-quality development level of China's higher education has steadily improved, with a growth rate of 2.85%. The spatial distribution exhibited a clustering pattern, with stable hotspot regions established in the eastern region characterized by significant "spillover" effects. Concurrently, the western regions narrowed the development gap compared with other areas. Scientific research represents the primary challenge to achieving high-quality development in higher education, with an average obstacle degree of 18.46%. Books per student, fixed assets per student, foreign technology imported per institution, research & development project funds, research & development projects per institution, and personnel investment in research & development projects were important constraints on the development of higher education in China and the provinces.Conclusions:Resource sharing and linkage need to be guaranteed by policy and institutional support, and each subject of higher education should give full play to its own advantages to contribute to the high-quality development of higher education through interregional linkage development, mutual synergy, and common progress.

As a new CRISPR/Cas-derived genome engineering technology, base editing combines the target specificity of CRISPR/Cas and the catalytic activity of nucleobase deaminase to install point mutations at target loci without generating DSBs, requiring exogenous template, or depending on homologous recombination. Recently, researchers have developed a variety of base editing tools in the important industrial strain Corynebacterium glutamicum, and achieved simultaneous editing of two and three genes. However, the multiplex base editing based on CRISPR/Cas9 is still limited by the complexity of multiple sgRNAs, interference of repeated sequence and difficulty of target loci replacement. In this study, multiplex base editing in C. glutamicum was optimized by the following strategies. Firstly, the multiple sgRNA expression cassettes based on individual promoters/terminators was optimized. The target loci can be introduced and replaced rapidly by using a template plasmid and Golden Gate method, which also avoids the interference of repeated sequence. Although the multiple sgRNAs structure is still complicated, the editing efficiency of this strategy is the highest. Then, the multiple gRNA expression cassettes based on Type Ⅱ CRISPR crRNA arrays and tRNA processing were developed. The two strategies only require one single promoter and terminator, and greatly simplify the structure of the expression cassette. Although the editing efficiency has decreased, both methods are still applicable. Taken together, this study provides a powerful addition to the genome editing toolbox of C. glutamicum and facilitates genetic modification of this strain.
CRISPR-Cas Systems/genetics* ; Corynebacterium glutamicum/metabolism* ; Gene Editing ; Plasmids ; RNA, Guide/metabolism*