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The aim of this study is to explore the mechanism by which ARHGAP4 regulates the proliferation and growth of colon cancer cells, and it relates to the metastasis of colorectal cancer (CRC). Various techniques including western blot, CCK8, qRT-PCR, RNA seq assay, plate cloning, subcutaneous tumorigenesis assays, and bioinformatics tools were employed to identify genes that were upregulated or downregulated upon ARHGAP4 knockdown and their involvement in tumor cell proliferation and growth. The expression of ARHGAP4 in T and M stages of CRC uses immunohistochemistry. The expression levels of ARHGAP4 were found to be high in SW620, SW480, and HCT116 cell lines, while they were being low in HT29, LoVo, and NCM460 cell lines. Depletion of ARHGAP4 resulted in inhibited proliferation and growth in SW620 cells and inhibited subcutaneous tumorigenesis in nude mice, whereas overexpression of ARHGAP4 promoted proliferation and growth in HT29 cells and promoted subcutaneous tumorigenesis in nude mice. A total of 318 upregulated genes and 637 downregulated genes were identified in SW620 cells upon ARHGAP4 knockdown. The downregulated genes were primarily associated with cell cycle pathways, while the upregulated genes were enriched in differentiation-related pathways. Notable upregulated genes involved in cell differentiation included KRT10, KRT13, KRT16, IVL, and CD24, while significant downregulation was observed in genes related to the cell cycle such as CCNA2, CDKN2C, CDKN3, CENPA, and CENPF. ARHGAP4 expression is markedly elevated in the M1 stage of CRC compared to the M0 stage, suggesting ARHGAP4 linked to the metastatic in CRC. ARHGAP4 regulates the proliferation and growth of colon cancer cells by up- and downregulated cell cycle and differentiation-related molecules, which may be related to the metastasis of CRC.
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Morphology regulation is an effective strategy for improving the sensor sensitivity of transition metal oxide nanostructures. In this work, SnO2 with three different morphologies (nanorods, nanoparticles, and nanopillars) has been synthesized by a simple one-step solvothermal process with the addition of various solute ratios at 180 °C for 6 h for detecting formaldehyde (HCHO) at the optimum working temperature of 320 °C. Compared to nanorods and nanopillars, the created SnO2 nanoparticles exhibit a much faster response time and sensitivity than other samples, showing the fastest recovery time (18 s) with the highest sensitivity of 6-100 ppm of the HCHO gas. The sensing mechanism of the sensors is investigated by Brunauer-Emmett-Teller (BET) methods and X-ray photoelectron spectroscopy (XPS) analysis, revealing that the pore size distribution and amount of OV and OC improve the charge transfer and HCHO adsorption of nanoparticle sensors. Such an effect of morphology control on sensing performance paves an idea for the development of different structure-based HCHO sensors.
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The utilization and selectivity of single atoms have garnered significant attention among researchers. However, they are easy to agglomerate because of their high surface energy. To overcome this challenge, it is crucial to seek suitable carriers to anchor single metal atoms to achieve optimal performance. In this work, the structures of transition metal single atoms embedded in hexagonal boron nitride (MB2N2, M = Fe, Co, Ni, Cu, Zn) are constructed and used for the adsorption and sensing of lithium battery thermal runaway gases (H2, CO, CO2, CH4) through the DFT method. The adsorption behavior of MB2N2 was evaluated through the adsorption energy, sensitivity, and recovery time. The calculation results indicate that CoB2N2 exhibits strong adsorption capacity for both H2 and CO. The sensitivity of FeB2N2 toward CO is as high as 3.232 × 1016. Subsequently, the adsorption mechanism was studied through TDOS and PDOS, and the results showed that hybridization between orbitals enhanced the gas adsorption performance. This study presents novel approaches for designing single-atom carriers and developing MB2N2 sensors for detecting lithium battery thermal runaway gases.
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The detection of hazardous CO gas is an important research content in the domain of the Internet of Things (IoT). Herein, we introduced a facile metal-organic frameworks (MOFs)-templated strategy to synthesize Cd-doped Co3O4 nanosheets (Cd-Co3O4 NSs) aimed at boosting the CO-sensing performance. The synthesized Cd-Co3O4 NSs feature a multihole nanomeshes structure and a large specific surface area (106.579 m2·g-1), which endows the sensing materials with favorable gas diffusion and interaction ability. Furthermore, compared with unadulterated Co3O4, the 2 mol % Cd-doped Co3O4 (2% Cd-Co3O4) sensor exhibits enhanced sensitivity (244%) to 100 ppm CO at 200 °C and a comparatively low experimental limit of detection (0.5 ppm/experimental value). The 2% Cd-Co3O4 NSs show good selectivity, reproducibility, and long-term stability. The improved CO sensitivity signal is probably owing to the stable nanomeshes construction, high surface area, and rich oxygen vacancies caused by cadmium doping. This study presents a facile avenue to promote the sensing performance of p-type metal oxide semiconductors by enhancing the surface activity of Co3O4 combined with morphology control and component regulation.
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This study aimed to analyze the differences in colorectal cancer (CRC) survival between urban and rural areas over the past 20 years, as well as investigate potential prognostic factors for CRC survival in both populations. Using registry data from Surveillance, Epidemiology, and End Results (SEER) from 2000 to 2019, 463,827 CRC cases were identified, with 85.8% in urban and 14.2% in rural areas. The mortality of CRC surpassed its survival rate by the sixth year after diagnosis in urban areas and the fifth year in rural areas. Furthermore, the 5-year overall survival (OS) of CRC increased by 2.9-4.3 percentage points in urban and 0.6-1.5 percentage points in rural areas over the past two decades. Multivariable Cox regression models identified independent prognostic factors for OS and disease-specific survival (DSS) of CRC in urban and rural areas, including age over 40, Black ethnicity, and tumor size greater than 5 cm. In addition, household income below $75,000 was found to be an independent prognostic factor for OS and DSS of CRC in urban areas, while income below $55,000 was a significant factor for rural areas. In conclusion, this study found a notable difference in CRC survival between rural and urban areas. Independent prognostic factors shared among both rural and urban areas include age, tumor size, and race, while household income seem to be area-specific predictive variables. Collaboration between healthcare providers, patients, and communities to improve awareness and early detection of CRC may help to further advance survival rates.
Subject(s)
Colorectal Neoplasms , Ethnicity , Humans , Prognosis , Rural Population , Survival Rate , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/diagnosisABSTRACT
BACKGROUND: RNA interference (RNAi) is the sequence-dependent suppression of gene expression by double-stranded RNA (dsRNA). This is a promising strategy for the control of insect pests because dsRNA can be rationally designed to maximize efficacy and biosafety, the latter by using sequences that are found in target pests but are safe for non-target insects. However, this has yet to be optimized in aphids, destructive sap-sucking pests that also transmit plant viruses. We used the green peach aphid (Myzus persicae) as a case study to optimize the efficiency of RNAi by applying a novel fusion dsRNA design. RESULTS: Comparative transcriptomics revealed a number of genes that are induced in feeding aphids, and eight candidate genes were chosen as RNAi targets. To improve RNAi efficiency, our fusion dsRNA design approach combined optimal gene fragments (highly conserved in several aphid species but with less homology in beneficial insects such as the predator ladybeetle Propylea japonica) from three candidate genes. We compared this RNAi-based biological control approach with conventional chemical control using imidacloprid. We found that the fusion dsRNA strategy inhibited the aphid population to a significantly greater extent than single-target RNAi and did not affect ladybeetle fitness, allowing an additive effect between RNAi and natural predation, whereas imidacloprid was harmful to aphids and ladybeetles. CONCLUSION: Our fusion dsRNA design approach enhances the ability of RNAi to control aphids without harming natural predators. © 2024 Society of Chemical Industry.
Subject(s)
Aphids , RNA Interference , RNA, Double-Stranded , Aphids/genetics , Animals , RNA, Double-Stranded/genetics , Coleoptera/genetics , Pest Control, Biological/methods , Insect Control/methods , Neonicotinoids/pharmacology , Nitro Compounds/pharmacologyABSTRACT
RNA binding proteins have been shown to regulate heart development and cardiac diseases. However, the detailed molecular mechanisms is not known. In this study, we identified Wilms' tumor 1-associating protein (WTAP, a key regulatory protein of the m6A RNA methyltransferase complex) as a key regulator of heart function and cardiac diseases. WTAP is associated with heart development, and its expression is downregulated in both human and mice with heart failure. Cardiomyocyte-specific knockout of Wtap (Wtap-CKO) induces dilated cardiomyopathy, heart failure and neonatal death. Although WTAP deficiency in the heart decreases METTL3 (methyltransferase-like 3) protein levels, cardiomyocyte-specific overexpression of Mettl3 in Wtap-CKO mice does not rescue the phenotypes of Wtap-CKO mice. Instead, WTAP deficiency in the heart decreases chromatin accessibility in the promoter regions of Mef2a (myocyte enhancer factor-2α) and Mef2c, leading to reduced mRNA and protein levels of these genes and lower expression of their target genes. Conversely, WTAP directly binds to the promoter of the Mef2c gene and increases its promoter luciferase activity and expression. These data demonstrate that WTAP plays a key role in heart development and cardiac function by maintaining the chromatin accessibility of cardiomyocyte specific genes.
Subject(s)
Cardiomyopathy, Dilated , Heart Failure , Animals , Humans , Mice , Cardiomyopathy, Dilated/genetics , Chromatin , Down-Regulation , Heart Failure/genetics , Methyltransferases , Myocytes, CardiacABSTRACT
To investigate the application of modified hexagonal boron nitride (h-BN) in the detection and monitoring of harmful gases (NO2, NO, NH3, and CO), first-principles calculations are applied to study the geometric structure and electronic behavior of the adsorption system. In this paper, the four adsorption sites, namely, B, N, bridge, and hollow sites, are considered to explore the stable adsorption structure of metals (M = Rh, Pd, Ag, Ir, Pt, and Au) on the BN surface. The calculation results demonstrate that the geometric structures of metal at the N-site are relatively stable. Subsequently, the different adsorption structures of NO2, NO, NH3, and CO on M-BN are researched. The electron transfer, charge difference density, and work function of the stable adsorption structure are calculated. The results show that NO2, NO, and CO have the strongest adsorption capacity in the Ir-BN system, with adsorption energies of -2.705, -5.064, and -3.757 eV, respectively. The Pt-BN system has an excellent adsorption performance (-2.251 eV) for NH3. Compared with the M-BN system, the work function of the adsorption system increases after adsorbing NO2, while it decreases after adsorbing NH3. This work shows that h-BN with metal modification is a potential material for online monitoring of harmful gases.
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<p><b>OBJECTIVE</b>To explore the expression of Cysleine-rich 61(Cyr61) gene in the different subtypes of myelodysplastic syndromes (MDS), and the significance of Cyr61 in the genesis progression, and transformation of MDS and the relationship between Cyr61 and vascular endothelial grown factor (VEGF).</p><p><b>METHODS</b>Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical S-P were used to detect mRNA and protein expressions of Cyr61 and VEGF in bone marrow mononuclear cells (BMMNC) from 28 MDS, 12 acute myeloid leukemia (AML) patients, and 10 normal volunteers.</p><p><b>RESULTS</b>Expressions of Cyr61 and VEGF were higher in MDS and AML patients than in controls (P < 0.05). The expressions of Cyr61 and VEGF were significantly higher in high risk group (0.3998 +/- 0.2647, 0.4775 +/- 0.1342) than that in low risk MDS group (0.2213 +/- 0.1465, 0.2872 +/- 0.2341) (P < 0.05), but no significant difference between high risk MDS and AML patients. Expressions of Cyr61 and VEGF protein were higher in MDS patients than in normal controls (P < 0.05), and were significantly higher in high risk MDS group \[(38.7 +/- 2.9)%, (43.2 +/- 2.7)%\] than in low risk group \[(31.4 +/- 3.1)%, (33.5 +/- 3.4)%\] (P < 0.05). Expressions of Cyr61 and VEGF were significantly correlated (r = 0.8762, P < 0.01).</p><p><b>CONCLUSION</b>Cyr61 and VEGF may play a role in the angiogenesis and pathogenesis of MDS.</p>
Subject(s)
Humans , Bone Marrow Cells , Metabolism , Cysteine , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Metabolism , Vascular Endothelial Growth Factor AABSTRACT
Objective To investigate the carrier ratio and the genotype of thalassemia among students of secondary school in Chongzuo, Guangxi. Methods From June 10-20,2008 among 7 regions of Chongzuo, 1 secondary school was randomly chosen from each region, and the number of student volunteers was determined by 0.5‰ proportion of the local population size. 1097 students were screened, including 515 boys and 582 girls of 12-16 year olds. Among them, 968 cases were Zhuang (438 boys and 530 girls) 128 cases were Han (76 boys and 52 girls) and one case was Yao nationalities (boy). Analysis of blood cells was detected by Cell Dyn 1700 automatic hemocyte analysator while hemoglobin F (HbF) and hemoglobin A2 (HbA2) were detected by hemoglobin autoanalyse variant. Among those with HbA2≥ 4% that belonged to β-thalassemia before α and β-thalassemia gene were analyzed to identify the genotypes. IfHbA2 was <4% but MCV≤80 fl, α-thalassemia gene was analyzed. Results Among 1097 cases,218 wereα-thalassemia (19.87%), 50 were β-thalassemia (4.56%) and 13 were combination of α β-thalassemia (1.19%). The overall detected ratio was 25.62%. 133 cases with thalassemia were boys (25.83%) and 148 were girls (25.43%) with no significant difference(P>0.05). 255 cases of thalassemia were Zhuang (26.34%), and 25 were Han nationality (19.52%). The detected ratio among Zhuang nationality was higher than in Hun nationality and with significant difference statistically (P<0.01). 3 kinds of deletion (-α3.7/,-α<4.2>/, --SEA/) and another 3 kinds of non-deletion (αα CS/, αα WS/, αα QS/) α-thalassemia genotype were identified, with a higher rate of ααWS/. Among the β-thalassemia genotype, CD41-42 appeared the most common genotype. MCV of thalassemia was lower than in the controls, with significant difference (P<0.01). 78-90 fl of α-thalassemia was detected from the MCV specimen. If taken MCV<79 fl as the positive phenotype of thalassemia, 32 cases were misdiagnosed. The rate of missed diagnosed cases was 2.97%. Conclusion Rate of thalassemia carder among students of secondary school in Chongzuo, Guangxi was considered to be high, especially those belonged to Zhuang nationality were higher than the Hans. The carrier rate of ααWS/was higher, with CD41-42 the most common genotype.
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To explore the expression of pituitary tumor-transforming gene (PTTG) in elderly patients with multiple myeloma (MM) and its relationship with MM, the expressions of PTTG mRNA were detected in bone marrow mononuclear cells (BMMNC) from 33 patients with MM and 10 normal controls by using reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed that the expression of PTTG mRNA in MM patients (0.3415 +/- 0.2172) was significantly higher than that in normal controls (0.0590 +/- 0.0233) (P < 0.05). It is concluded that the overexpression of oncogene PTTG may be related to genesis and progression of MM. It provided a new ideas to study the pathogenesis and gene therapy for MM patients.