Determination of carbohydrate content in kenaf degumming wastewater and converting them to carbon dots.

The traditional textile degumming process produces abundant wastewater, which contains a lot of monosaccharides and oligosaccharides. It is of great economic and environmental significance to utilize these carbohydrates in high value. In this study, high performance liquid chromatography (HPLC) was used to analyze the carbohydrate components in kenaf degumming wastewater, and then the production of C-dots using the wastewater was explored. The results showed that the types and content in the degumming wastewater were monosaccharides (glucose, xylose and arabinose) and oligosaccharides (dextran, xylan and araban). The carbohydrate (mainly glucan and xylan) content in wastewater accounted for 91.16 % of the total carbohydrates weight loss in kenaf degumming process. By using hydrolysis and hydrothermal reaction on kenaf degumming wastewater, blue-green carbon dots (C-dots) with good performance were prepared and successfully applied to anti-counterfeiting printing. In particular, the as-prepared C-dots prepared from kenaf degumming wastewater with urea added (WUC-dots) showed an excitation-dependent photoluminescence (PL) spectrum and quantum yield (QY) of 2.4 % in aqueous solution. The fluorescent code exhibited a clear outline, excitation-tunable color and good stability, showing a great potential for anti-counterfeiting system.

Decreasing hydrophobicity or shielding hydrophobic areas of CH2 attenuates low pH-induced IgG4 aggregation.

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.

Establishment and validation of prognostic nomogram in acute leukemia with trisomy 8.

OBJECTIVE: This study aims to construct a nomogram model for predicting poor prognosis in acute leukemia with trisomy 8. METHODS: 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. RESULTS: 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 χ2 = 6.507, P = 0.448, and the area under the ROC curve was 0.834 (95%CI: 0.748-0.921). CONCLUSION: The nomogram model constructed in this study for predicting poor prognosis among acute leukemia patients with trisomy 8 demonstrates excellent discrimination and consistency.

Insights Into the Mechanism of Tyrosine Nitration in Preventing ß-Amyloid Aggregation in Alzheimer's Disease.

Nitration of tyrosine at the tenth residue (Tyr10) in amyloid-ß (Aß) has been reported to reduce its aggregation and neurotoxicity in our previous studies. However, the exact mechanism remains unclear. Here, we used Aß1-42 peptide with differently modified forms at Tyr10 to investigate the molecular mechanism to fill this gap. By using immunofluorescent assay, we confirmed that nitrated Aß 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 Aß 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 Aß could not inhibit Aß fibrilization and aggregation. Nitration of Aß reduces its aggregation mainly because it could induce the deprotonation of the phenolic hydroxyl group of Tyr10 of Aß 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 Aß fibrilization and aggregation. These findings provide us new insights into the relationship between Tyr10 nitration and Aß aggregation, which would help to further understand that keeping the balance of nitric oxide in vivo is important for preventing AD.

Inhibition of N-acetylglucosaminyltransferase V enhances sensitivity of radiotherapy in human prostate cancer.

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.

Genetic polymorphisms in inflammatory response genes and their associations with breast cancer risk.

AIM: To explore the association of NFKB1 c.-798_-795delATTG (rs28362491), NFKBIA c.-949C>T (rs2233406), IL-8 c.-352A>T (rs4073), IL-10 c.-854T>C (rs1800871), TNF c.-418G>A (rs361525), and TNF c.-488G>A (rs1800629) polymorphisms with breast cancer risk in an East Chinese population. METHODS: We conducted a case-control study including 975 study participants (474 breast cancer patients and 501 female controls without cancer) and genotyped the polymorphisms employing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic regression was used to assess the association of the polymorphisms with breast cancer risk. RESULTS: We found that the ins/del and del/del genotypes of NFKB1 polymorphism and TT genotype of IL-10 polymorphism significantly increased breast cancer risk (NFKB1 ins/del odds ratio [OR] 1.69, 95% [CI] 1.23-2.33, P=0.001; NFKB1 del/del OR 2.42, 95% CI 1.72-3.42, P<0.001; IL-10 TT OR 2.36, 95% CI 1.58-3.52, P<0.001). On the other hand, the TT genotype of IL-8 polymorphism, GA and AA genotypes of TNF c.-418G>A polymorphism, and GA genotype of TNF c.-488G>A polymorphism significantly reduced breast cancer risk (IL-8 TT OR 0.48, 95% CI 0.33-0.72, P<0.001; TNF c.-418 GA OR 0.58, 95% CI 0.41-0.80, P=0.001; TNF c.-418 AA OR 0.38, 95% CI 0.14-0.98, P=0.044; TNF c.-488 GA OR 0.68, 95% CI 0.48-0.96, P=0.029). When stratified by menopausal status, the CT genotype of NFKBIA polymorphism significantly reduced the risk among pre-menopausal women (OR 0.63, 95% CI 0.40-0.99, P=,043), but not among post-menopausal women. CONCLUSIONS: NFKB1, NFKBIA, IL-8, IL-10, and TNF polymorphisms could serve as useful predictive biomarkers for breast cancer risk among women in East China.

The role of N-acetylglucosaminyltransferases V in the malignancy of human hepatocellular carcinoma.

To investigate the role of N-acetylglucosaminyltransferases V (GnT-V) in the malignancy of human hepatocellular carcinoma (HCC), the GnT-V stably suppressed cell line HepG2 GnT-V/1564 was constructed from HepG2. The proliferation, migration, invasion, metastasis of HepG2 GnT-V/1564 was investigated both in vitro and in vivo. The clinical pathological significance of GnT-V expression was also studied in 140 cases of HCC tissues. This study showed that down-regulation of GnT-V inhibited the proliferation, migration and invasion of the HepG2 cells. In addition, GnT-V expression was shown in 138 cases of 140 (98.6%) HCC samples, in 3 cases of 31 (9.7%) in liver cirrhosis cases and in 1 cases of 20 (5.0%) in normal liver tissues. Besides, a higher level of GnT-V was observed more frequently in the advanced tumors with higher T stage and histological grade. These data suggested that GnT-V expression was positively related with malignancy in HCC and GnT-V may be both a differentiation marker and a potential target for the treatment of HCC.