Arsenic trioxide regulates the glycolytic pathway to treat acute promyelocytic leukemia by inhibiting RPL22L1.

OBJECTIVE: To investigate the relationship between the treatment of acute promyelocytic leukemia (APL) with arsenic trioxide (ATO) and glycolysis, as well as its underlying molecular mechanism. METHODS: The GEO database was used to analyze alterations in the expression of RPL22L1 in APL patients and its correlation with glycolysis. The levels of RPL22L1 and glycolysis were assessed in 9 paired clinical samples. NB4 cells and NB4 cells with knockdown of RPL22L1 were treated with ATO. The protein and mRNA of RPL22L1 were detected using RT-PCR and Western blot, and the content was determined by using glucose, pyruvate, and lactate detection kits. Finally, detection of cell proliferation using CCK8, migration by scratch assay, and apoptosis by flow cytometry, and the biological function of ATO in NB4 cells was examined. RESULTS: The expression of RPL22L1 in GSE213742 and GSE234103 datasets exhibited a significant increase in human APL cells, specifically NB4 cells. RPL22L1 in GSE213742 and GSE234103 gene expression matrix was significantly elevated in human APL cells NB4 cells, and further analysis found RPL22L1 showed a strong positive correlation with glycolysis. Cellular experiments showed that ATO inhibited RPL22L1 in NB4 cells and inhibited glycolysis in APL cells. The ATO played a pivotal role in suppressing the proliferation, migration, as well as invasion of NH4 cells. CONCLUSION: ATO regulates the blycolytic pathway in APL by inhibiting RPL22L1 expression, and this may contribute to its therapeutic effects.

Pancancer Analysis of Revealed TDO2 as a Biomarker of Prognosis and Immunotherapy.

Background: Tryptophan 2,3-dioxygenase (TDO) encoded by TDO2, a rate-limiting enzyme in the kynurenine pathway, catabolizes tryptophan to kynurenine, evades immune surveillance, and promotes tumor growth. Although accumulating evidence suggests a crucial role of TDO2 during tumor formation and development, systematic evaluation of TDO2 across human cancers has rarely been reported. Methods: To shed more light on the role of TDO2 in human cancer, we explored the expression profiles of TDO2 and identified its prognostic value in pancancer analysis through TCGA, CCLE, and GTEx databases. We further utilized TCGA data to evaluate the association between TDO2 and tumor immunological features, such as mismatch repair (MMR), tumor immune infiltration, immune checkpoint-related genes, tumor mutational burden (TMB), microsatellite instability (MSI), and DNA methyltransferase (DNMT). Results: TDO2 exhibited different expression levels in various cancer cell lines. Frequently, TDO2 was detected to be highly expressed in the majority of cancers. In addition, high TDO2 expression was correlated with an unfavorable prognosis for patients in KIRP, LGG, TGCT, and UVM. Moreover, high TDO2 expression level positively correlated with higher immune infiltration, especially dendritic cells. Additionally, there is a close relationship between TDO2 and immune checkpoint-related gene markers, such as LAIR1, CD276, NRP1, CD80, and CD86. Finally, correlation analysis has demonstrated a high-correlation between TDO2 and TMB, MSI, MMR, and DNMT of multiple cancer types. Conclusion: Therefore, our results suggest that TDO2 can function as a potential prognostic biomarker due to its role in tumor immunity regulation.

Pelvic incidence: A study of a spinopelvic parameter in MRI evaluation of pelvic organ prolapse.

PURPOSE: This study aims to compare pelvic incidence (PI), a skeletal angle formed by the first sacral vertebrae and femoral heads, in women with and without pelvic organ prolapse (POP) and to explore the correlation of PI with the progression of POP, through 3D reconstruction of MRI scans. METHOD: The case-control study enrolled 48 prolapse patients and 48 paired subjects by collecting and screening clinical information including age, BMI, vaginal deliveries, and levator ani defect scores. PI values were measured in 3D reconstruction models based on MRI scans, and the mean and standard deviation values of PI in both groups were calculated. Receiver operating characteristic (ROC) analysis and logistic regression were used to quantify relationships between PI and prolapse. Additionally, by performing a cross-section study of 69 patients with POP, correlations between PI values and descending vaginal locations were assessed by multivariate linear regression models. RESULTS: Compared with the control group, the patient group has a significantly larger average PI (48.68 ±â€¯10.77˚ vs 42.20 ±â€¯8.55˚, P=0.002). ROC analysis for the classification of prolapse based on PI has an area under the curve of 70.1 % (P < 0.001). Logistic regression identified a larger PI value as a risk factor of prolapse with an odds ratio of 2.90 (95 %CI: 1.46-5.74, P = 0.002) for PI per increasing 10˚. Point Ba and Bp represent the most distal positions of any part of the upper anterior and posterior vaginal walls, respectively. In the patient group, internally, Ba and Bp would descend 0.62 (95 %CI: 0.24-1.00, P=0.002) cm and 0.74 (95 %CI 0.22-1.26, P=0.006) cm for every 10° increase in PI, respectively. The coefficients of the partial correlation of PI for Ba and Bp are 0.381 (P = 0.002) and 0.336 (P = 0.006). CONCLUSIONS: PI is significantly related to morbidity and progression of POP, especially for the anterior and posterior pelvic compartments. As an individual constant value of the spinopelvic skeletal shape, a larger PI value is a risk factor and should be evaluated carefully in medical imaging of POP.

Nonlinear optical properties of near-infrared region Ag2S quantum dots pumped by nanosecond laser pulses.

This study investigates near-infrared region Ag2S quantum dots (QDs) and their nonlinear optical response under 532 nm nanosecond laser pulses. Our experimental result shows that nonlinear transmission is reduced from 0.084 to 0.04. The observed narrowing behavior of the output pulse width shows superior optical limiting. We discuss the physical mechanisms responsible for the nonlinear optical response of the QDs. The average size of the nanocrystals was 5.5 nm. Our results suggest the possibility of using these Ag2S QDs for photoelectric, biosensor, optical ranging, and self-adaptive technologies.

Creating ligand-free silicon germanium alloy nanocrystal inks.

Particle size is widely used to tune the electronic, optical, and catalytic properties of semiconductor nanocrystals. This contrasts with bulk semiconductors, where properties are tuned based on composition, either through doping or through band gap engineering of alloys. Ideally, one would like to control both size and composition of semiconductor nanocrystals. Here, we demonstrate production of silicon-germanium alloy nanoparticles by laser pyrolysis of silane and germane. We have used FTIR, TEM, XRD, EDX, SEM, and TOF-SIMS to conclusively determine their structure and composition. Moreover, we show that upon extended sonication in selected solvents, these bare nanocrystals can be stably dispersed without ligands, thereby providing the possibility of using them as an ink to make patterned films, free of organic surfactants, for device fabrication. The engineering of these SiGe alloy inks is an important step toward the low-cost fabrication of group IV nanocrystal optoelectronic, thermoelectric, and photovoltaic devices.