Multi-omics profiling combined with molecular docking reveals immune-inflammatory proteins as potential drug targets in colorectal cancer.

Colorectal cancer is globally ranked as the third most common malignant tumor. Its development involves a complex biological process driven by various genetic and epigenetic alterations. To elucidate the biological significance of the extensive omics data, we conducted comparative multi-omics studies on colorectal cancer patients at different clinical stages. Bioinformatics methods were applied to analyze multi-omics datasets and explore the molecular landscape. Drug prediction and molecular docking also were conducted to assess potential therapeutic interventions. In vitro experiments were used to validate the inhibitory effect on the migration and proliferation of cell lines. The results indicate up-regulated proteins involved in immune-inflammatory related pathways, while biomarkers related to muscular contraction and cell adhesion are significantly down-regulated. Drug prediction, coupled with in vitro experiments, suggests that AZ-628 may act as a potential drug to inhibit the proliferation and migration of CRC cell lines HCT-116 and HT-29 by regulating the aforementioned key biological pathways or proteins. Complementing these findings, metabolomics analysis unveiled a down-regulation of key carbon metabolism pathways, alongside an up-regulation in amino acid metabolism, particularly proline metabolism. This metabolic shift may reflect an adaptive response in cancer cells, favoring specific amino acids to support their growth. Together, these integrated results provide valuable insights into the intricate landscape of tumor development, highlighting the crossroads of immune regulation, cellular structure, and metabolic reprogramming in the tumorigenic process and providing valuable insights into cancer pathology.

Establishment of pregnant-specific intervals for hemoglobin (Hb) A2, HbF and cut-off points for HbA2 for thalassemia in Chongqing, China.

OBJECTIVES: To analyze pregnant-specific intervals for hemoglobin A2 (HbA2), hemoglobin fetal (HbF), and cut-off points of HbA2 for thalassemia in Chongqing, China. METHODS: Between September 2015 and April 2019, the study recruited 10039 individuals of reproductive age. Of which, 4399 healthy normal individuals were selected to determine reference values for HbA2 and HbF. The remaining 5640 individuals suspected of thalassemia were included to explore the cut-off points of HbA2 for thalassemia. RESULTS: The reference values of HbA2 in males was 2.3-3.2%, in females was 2.1-3.1%, and in pregnant women was 1.9-3.1%. While the reference values of HbF in males was 0.0-0.0%, in females was 0.0-0.9%, and in pregnant women was 0.0-4.3%. Approximately 2.3% cut-off points for pregnant women was determined to be optimal for α-thalassemia screening. In the entire group, 2.5% was best for all α-thalassemia screenings. The cut-off for ß-thalassemia screening using HbA2 was 3.2% for the entire group. CONCLUSION: The reference interval of HbA2 for pregnant females group was significantly lower than other groups. Therefore, we recommend cut-off points of HbA2 for α-thalassemia at 2.3% for pregnant women. While partitioning was not needed due to gender. Gender and pregnancy had little effect on the cut-off points of HbA2 for ß-thalassemia carrier.

[Hematological Characteristics of Different Genotypes of Thalassemia among Reproductive Population in Chongqing].

OBJECTIVE: To investigate the hematological characteristics and genotype distribution of thalassemia among people at reproductive age in Chongqing. METHODS: Hematology analysis and capillary electrophoresis were performed in 29 145 participants at reproductive age. The patients with positive results were confirmed by thalassemia genotyping. Genotype distribution and characteristics of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and hba2 levels in thalassemia patients were analyzed. RESULTS: --SEA/αα (45.10%), -α3.7/αα (39.31%) and -α4.2/αα (8.46%) were the most common genotypes of α-thalassemia, while CD17 (HBB: c. 52A>T) (31.67%), CD41-42 (HBB: c. 126-129 del TTCT) (26.87%) and IVS-Ⅱ-654 (HBB: c. 316-197 C>T) (24.21%) were the most common genotypes of ß-thalassemia in Chongqing. In α-thalassemia ααCS/αα showed the lowest hba2 value (2.18±0.23)%, while --SEA/αα showed the lowest MCV (71.9±8.5) fl and MCH (22.7±3.3) pg value. The patients in ßE (HBB: c. 79G>A) group showed comparatively higher values of MCV and MCH and significantly lower HbA and hba2 values than the other genotypes. There was no significant difference in HbA, hba2, MCV, MCH levels of the patients between pregnant group and non-pregnant group. CONCLUSIONS: In Chongqing, there are differences in hematological characteristics among patients with different thalassemia genotypes. There is no significant effect of pregnancy on HbA, hba2, MCV and MCH has been found.

Managing Defects Density and Interfacial Strain via Underlayer Engineering for Inverted CsPbI2 Br Perovskite Solar Cells with All-Layer Dopant-Free.

Inorganic perovskite CsPbI2 Br has advantages of excellent thermal stability and reasonable bandgap, which make it suitable for top layer of tandem solar cells. Nevertheless, solution-processed all-inorganic perovskites generally suffer from high-density defects as well as significant tensile strain near underlayer/perovskite interface, both leading to compromised device efficiency and stability. In this work, the defect density as well as interfacial tensile strain in inverted CsPbI2 Br perovskite solar cells (PeSCs) is remarkably reduced by using a bilayer underlayer composed of dopant-free 2,2',7,7'-tetrakis(N,N-dip-methoxyphenylamine)-9,9'-spirobifluorene (Spiro-OMeTAD) and copper phthalocyanine 3,4',4″,4'″-tetrasulfonated acid tetrasodium salt (TS-CuPc) nanoparticles. As compared to control devices with pristine Spiro-OMeTAD, devices based on Spiro-OMeTAD/TS-CuPc exhibit remarkably improved photovoltaic performance and enhanced thermal/humidity stability due to the better perovskite crystallization, improved interfacial passivation, and hole-collection as well as efficient interfacial strain release. As a result, a champion efficiency of 14.85% can be achieved, which is approaching to the best reported for dopant-free and inverted all-inorganic PeSCs. The work thus provides an efficient strategy to simultaneously regulate the defects density and strain issue related to inorganic perovskites.

[Influence of Iron Deficiency on the Index of Thalassemia Screening].

OBJECTIVE: To investigate the influence of iron deficiency on the index of thalassemia screening. METHODS: 876 blood samples of the couples at childbearing age, who underwent red blood cell analysis, hemoglobin electrophoresis, ferritin and gene diagnosis were selected. The samples were divided into normal, iron deficiency, αthalassemia, α-thalassemia combining with iron deficiency, ß-thalassemia and ß-thalassemia combining with iron deficiency group. The differences of hematology index and hemolobin value A2 between each groups were analyzed. RESULTS: The value of Hb, MCV, MCH, MCHC in iron deficiency, αthalassemia, α-thalassemia combining with iron deficiency, ß-thalassemia and ß-thalassemia combining with iron deficiency group all were lower than that of normal group, while the value of RDW-CV was higher, in which the difference between ß-thalassemia was the highest. The distribution of HbA2 among each groups was not significantly different expect of ß-thalassemia. There was no significant correlation between HbA2 and ferritin level. CONCLUSION: RDW-CV increases in both iron deficiency and thalassemia. Iron deficiency has no significant effect on the level of hemoglobin A2.