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Ziyuan Shen,1,* Fei Wang,2,* Chenlu He,1,* Dashan Li,3 Shanlin Nie,3 Zhenzhen Bian,3 Mingkang Yao,4 Yuhao Xue,5 Ying Wang,6 Weiying Gu,2 Taigang Zhu,7 Yuye Shi,5 Hao Zhang,4 Shuiping Huang,1,8 Yuqing Miao,9 Wei Sang3 On behalf of the Huaihai Lymphoma Working Group1Department of Epidemiology and Biostatistics, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Department of Hematology, The First People’s Hospital of Changzhou, Changzhou, Jiangsu, People’s Republic of China; 3Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 4Department of Hematology, Affiliated Hospital of Jining Medical University, Jining, Shandong, People’s Republic of China; 5Department of Hematology, The First People’s Hospital of Huaian, Huaian, Jiangsu, People’s Republic of China; 6Department of Personnel, Suqian First Hospital, Suqian, Jiangsu, People’s Republic of China; 7Department of Hematology, The General Hospital of Wanbei Coal-Electric Group, Suzhou, People’s Republic of China; 8Center for Medical Statistics and Data Analysis, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 9Department of Hematology, Yancheng First People’s Hospital, Yancheng, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei SangDepartment of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of ChinaTel +8613645207648Email xyfylbl515@xzhmu.edu.cnYuqing MiaoDepartment of Hematology, Yancheng First People’s Hospital, Yancheng, Jiangsu, People’s Republic of ChinaTel +8613851342032Email miaomiaomyq@163.comIntroduction: Immunonutritional status is associated with the survival of DLBCL. This multicenter retrospective study aimed to explore the prognostic value of Prognostic Nutrition Index (PNI) in DLBCL patients by using propensity score matched analy

Allostery is defined as the functional regulation at one site in a protein by activity at a distant site. Because of the ubiquitous occurrence and diverse cellular roles of allosteric proteins, designing novel allosteric proteins is of great interest for applications in synthetic biological and disease treatment. However, the engineering of allostery is often hindered by our limited understanding of the protein sequence- function relationship, especially at residue positions that are distant from functional sites or evolutionarily nonconserved. In this dissertation, the sequence-function relationship was investigated in the Escherichia coli biotin protein ligase (BirA) system, which serves as both an essential metabolic enzyme and a transcription regulator. In its repressor function, binding to the vitamin biotin allosterically activates BirA dimerization and the resulting repression complex assembly on the biotin operator sequence. Although the allosteric regulation is conserved among bifunctional biotin protein ligases such as BirA, their sequences, even those of functional importance, are highly divergent. The in vitro characterization of BirA super repressor variants reveals that the sensitivity of transcription repression response to input biotin concentration can be altered solely through substitution-perturbed dimerization. These single amino acid substitutions are located at sites scattered throughout the protein structure including some that are distal from the BirA dimerization surface. Computational simulations indicate that the long-range effect of substitutions on dimerization results from rearrangement of a residue network that contributes to the allosteric activation in BirA. Several loops on the BirA dimerization surface were characterized for their roles in the corepressor-induced dimerization. The study of nonconserved amino acid positions spanning these surface loops reveals that a broad range of functional response in dimerization and transcripti