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This study aims to construct a nomogram model for predicting poor prognosis in acute leukemia with trisomy 8. A retrospective analysis was conducted on 244 patients with primary acute leukemia with trisomy 8 who received treatment in our hospital, and they were randomly divided into the modeling group (122 cases, including 78 cases with good prognosis and 44 cases with poor prognosis) and the verification group (122 cases). R software was used to construct a nomogram model for predicting poor prognosis in acute leukemia with trisomy 8. The results of multivariate analysis showed that age >51 years old, and white blood cell count ≤20 × 109/L were risk factors for poor prognosis in acute leukemia patients with trisomy 8 (P < 0.05), and chemotherapy + transplantation was a protective factor for poor prognosis in acute leukemia patients with trisomy 8 (P < 0.05). The nomogram for poor prognosis of acute leukemia patients with trisomy 8 was constructed using the above four risk predictors. The Hosmer-Lemeshow goodness of fit test was = 6.371, P = 0.497, and the area under the ROC curve was 0.817 (95%CI: 0.742-0.892). The slope of the calibration curve of external validation was close to 1, Hosmer-Lemeshow goodness of fit test was $\chi ^2$ χ 2 = 6.507, P = 0.448, and the area under the ROC curve was 0.834 (95%CI: 0.748-0.921). The nomogram model constructed in this study for predicting poor prognosis among acute leukemia patients with trisomy 8 demonstrates excellent discrimination and consistency. [ABSTRACT FROM AUTHOR]

Nitration of tyrosine at the tenth residue (Tyr10) in amyloid-β (Aβ) has been reported to reduce its aggregation and neurotoxicity in our previous studies. However, the exact mechanism remains unclear. Here, we used Aβ1–42 peptide with differently modified forms at Tyr10 to investigate the molecular mechanism to fill this gap. By using immunofluorescent assay, we confirmed that nitrated Aβ was found in the cortex of 10-month-old female triple transgenic mice of Alzheimer's disease (AD). And then, we used the surface-enhanced Raman scattering (SERS) method and circular dichroism (CD) to demonstrate that the modification and mutation of Tyr10 in Aβ have little impact on conformational changes. Then, with the aids of fluorescence assays of thioflavin T and 4,4′-dianilino-1,1′-binaphthyl-5,5′-disulfonic acid, transmission electron microscopy (TEM), atomic force microscopy (AFM), and dynamic light scattering (DLS), we found that adding a large group to the phenolic ring of Tyr10 of Aβ could not inhibit Aβ fibrilization and aggregation. Nitration of Aβ reduces its aggregation mainly because it could induce the deprotonation of the phenolic hydroxyl group of Tyr10 of Aβ at physiological pH. We proposed that the negatively charged Tyr10 caused by nitration at physiological pH could interact with the salt bridge between Glu11 and His6 or His13 and block the kink around Tyr10, thereby preventing Aβ fibrilization and aggregation. These findings provide us new insights into the relationship between Tyr10 nitration and Aβ aggregation, which would help to further understand that keeping the balance of nitric oxide in vivo is important for preventing AD. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the relationship between N-acetylglucosaminyltransferase V (GnT-V) and radiation sensitivity of prostate cancer (PCa) cells both in vitro and in vivo. Firstly, the GnT-V expression was studied in 84 cases of PCa tissues, in which higher level of GnT-V was detected more frequently in the advanced tumors. Secondly, the GnT-V stably suppressed cell lines PCa/1079 (Lncap/1079 and PC3/1079) were constructed from PCa cell lines (Lncap and PC3) in vitro. Attenuation of GnT-V inhibited cell proliferation, migration and increased apoptosis, which resulted in enhanced radiation sensitivity of PCa cells. The underlying mechanism may be relevant to the increasing ratio of Bax/Bcl-2, the blocking transcription of NF-κB and the reduction of cell cycle G2-M arrest. Finally, in in vivo study, compared with control groups, the irradiated PCa xenograft nude mice of PCa/1079 indicated to reduce tumor-growth rate and enhance survival time. Summary, our studies showed that inhibition of GnT-V probably improved PCa cells’ radiation sensitivity. [ABSTRACT FROM AUTHOR]

Protein aggregation is a major challenge in the development of therapeutic monoclonal antibodies (mAbs). Several stressors can cause protein aggregation, including temperature shifts, mechanical forces, freezing-thawing cycles, oxidants, reductants, and extreme pH. When antibodies are exposed to low pH conditions, aggregation increases dramatically. However, low pH treatment is widely used in protein A affinity chromatography and low pH viral inactivation procedures. In the development of an IgG4 subclass antibody, mAb1-IgG4 showed a strong tendency to aggregate when temporarily exposed to low pH conditions. Our findings showed that the aggregation of mAb1-IgG4 under low pH conditions is determined by the stability of the Fc. The CH2 domain is the least stable domain in mAb1-IgG4. The L309E, Q311D, and Q311E mutations in the CH2 domain significantly reduced the aggregation propensity, which could be attributed to a reduction in the hydrophobicity of the CH2 domain. Protein stabilizers, such as sucrose and mannose, could also attenuate low pH-induced mAb1-IgG4 aggregation by shielding hydrophobic areas and increasing protein stability. Our findings provide valuable strategies for managing the aggregation of protein therapeutics with a human IgG4 backbone., Competing Interests: QW, CC, KC, LS, QL, and JL were employed by the company Zhuhai United Laboratories Co., Ltd. CC, SW, and HH were employed by the company The United Biotechnology (Zhuhai Hengqin) Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Cao, Wei, He, Chen, Su, Liu, Li, Lai and Li.)