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1.
J Appl Genet ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38568413

RESUMO

The identification of biomarkers correlated with colorectal cancer (CRC) prognosis holds substantial importance from both clinical and scientific perspectives. Zinc finger protein 26 (ZNF26) has not been previously investigated or documented in solid tumors; thus, further research is necessary to ascertain its prognostic value in CRC. Gene expression profiles and clinicopathological data were acquired from The Cancer Genome Atlas (TCGA) database. Subsequently, expression correlation was assessed utilizing the TCGA CRC cohort. The prognostic value of ZNF26 was evaluated through Kaplan-Meier (KM) and ROC curve analyses. Following this, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to perform enrichment analysis between high- and low-ZNF26 expression groups. The association between immune cells, immune checkpoint genes, and ZNF26 expression levels was examined. Lastly, the research findings were further validated using CRC tissue samples. The results revealed that, in comparison to healthy controls, CRC significantly reduced ZNF26 expression. Elevated ZNF26 expression was associated with poorer overall survival in CRC patients. Additionally, high ZNF26 expression exhibited an inverse relationship with the immunological score and immune checkpoint gene expression in CRC patients. The findings from the TCGA data analysis were corroborated by the PCR results obtained from CRC tissue samples. ZNF26 is markedly upregulated in colorectal cancer tissues, potentially serving as a biomarker for CRC.

2.
J Integr Plant Biol ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578173

RESUMO

Leaves are the main photosynthesis organ that directly determines crop yield and biomass. Dissecting the regulatory mechanism of leaf development is crucial for food security and ecosystem turn-over. Here, we identified the novel function of R2R3-MYB transcription factors CsRAXs in regulating cucumber leaf size and fruiting ability. Csrax5 single mutant exhibited enlarged leaf size and stem diameter, and Csrax1/2/5 triple mutant displayed further enlargement phenotype. Overexpression of CsRAX1 or CsRAX5 gave rise to smaller leaf and thinner stem. The fruiting ability of Csrax1/2/5 plants was significantly enhanced, while that of CsRAX5 overexpression lines was greatly weakened. Similarly, cell number and free auxin level were elevated in mutant plants while decreased in overexpression lines. Biochemical data indicated that CsRAX1/5 directly promoted the expression of auxin glucosyltransferase gene CsUGT74E2. Therefore, our data suggested that CsRAXs function as repressors for leaf size development by promoting auxin glycosylation to decrease free auxin level and cell division in cucumber. Our findings provide new gene targets for cucumber breeding with increased leaf size and crop yield.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38588675

RESUMO

Modulating interlayer coupling modes can effectively enhance the thermoelectric properties of nano materials or nanoscale devices. By using density functional theory (DFT) combined with non-equilibrium Green's function (NEGF) method, we investigate the thermoelectric properties of zigzag-type black arsenic nanoscale devices with varying interlayer coupling modes. Our results show that altering the interlayer coupling mode significantly modulates the thermoelectric properties of the system. Specifically, we consider four coupling modes with different strengths, by modulating different interlayer overlap patterns. Notably, in the weaker interlayer coupling mode, the system exhibits enhanced thermoelectric properties due to increased interface phonon scattering, reaching a peak value of 2.23 at µ =-0.73eV. Furthermore, we explore the temperature-dependent behavior of each coupling model. The results suggest that the thermoelectric characteristics are more sensitive to temperature variations in the weaker coupling modes. These insights provide valuable guidance for enhancing the thermoelectric performance of nano-scale devices through precise interlayer coupling modulation.

4.
Opt Express ; 32(6): 8847-8861, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571132

RESUMO

In this paper, we propose an optomechanical scheme for generating mechanical squeezing over the 3 dB limit, with the mechanical mirror being driven by a strong and linear harmonic force. In contrast to parametric mechanical driving, the linearly driven force shakes the mechanical mirror periodically oscillating at twice the mechanical eigenfrequency with large amplitude, where the mechanical mirror can be dissipatively stabilized by the engineered cavity reservoir to a dynamical squeezed steady state with a maximum degree of squeezing over 8 dB. The mechanical squeezing of more than 3 dB can be achieved even for a mechanical thermal temperature larger than 100 mK. The scheme can be implemented in a cascaded optomechanical setup, with potential applications in engineering continuous variable entanglement and quantum sensing.

5.
Proteomics ; : e2300222, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581091

RESUMO

The group 2 σ factor for RNA polymerase SigE plays important role in regulating central carbon metabolism in cyanobacteria. However, the regulation of SigE for these pathways at a proteome level remains unknown. Using a sigE-deficient strain (ΔsigE) of Synechocystis sp. PCC 6803 and quantitative proteomics, we found that SigE depletion induces differential protein expression for sugar catabolic pathways including glycolysis, oxidative pentose phosphate (OPP) pathway, and glycogen catabolism. Two glycogen debranching enzyme homologues Slr1857 and Slr0237 are found differentially expressed in ΔsigE. Glycogen determination indicated that Δslr0237 accumulated glycogen under photomixotrophic condition but was unable to utilize these reserves in the dark, whereas Δslr1857 accumulates and utilizes glycogen in a similar way as the WT strain does in the same condition. These results suggest that Slr0237 plays the major role as the glycogen debranching enzyme in Synechocystis.

6.
Heliyon ; 10(7): e29299, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38623252

RESUMO

Early mutation identification guides patients with colorectal cancer (CRC) toward targeted therapies. In the present study, 414 patients with CRC were enrolled, and amplicon-based targeted next-generation sequencing (NGS) was then performed to detect genomic alterations within the 73 cancer-related genes in the OncoAim panel. The overall mutation rate was 91.5 % (379/414). Gene mutations were detected in 38/73 genes tested. The most frequently mutated genes were TP53 (60.9 %), KRAS (46.6 %), APC (30.4 %), PIK3CA (15.9 %), FBXW7 (8.2 %), SMAD4 (6.8 %), BRAF (6.5 %), and NRAS (3.9 %). Compared with the wild type, TP53 mutations were associated with low microsatellite instability/microsatellite stability (MSI-L/MSS) (P = 0.007), tumor location (P = 0.043), and histological grade (P = 0.0009); KRAS mutations were associated with female gender (P = 0.026), distant metastasis (P = 0.023), TNM stage (P = 0.013), and histological grade (P = 0.004); APC mutations were associated with patients <64 years of age at diagnosis (P = 0.04); PIK3CA mutations were associated with tumor location (P = 4.97e-06) and female gender (P = 0.018); SMAD4 mutations were associated with tumor location (P = 0.033); BRAF mutations were associated with high MSI (MSI-H; P = 6.968e-07), tumor location (P = 1.58e-06), and histological grade (P = 0.04). Mutations in 164 individuals were found to be pathogenic or likely pathogenic. A total of 26 patients harbored MSI-H tumors and they all had at least one detected gene mutation. Mutated genes were enriched in signaling pathways associated with CRC. The present findings have important implications for improving the personalized treatment of patients with CRC in China.

7.
BMC Oral Health ; 24(1): 461, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627719

RESUMO

BACKGROUND: It is uncertain if mean platelet volume and periodontitis are related. The objective of this study was to examine the association between levels of mean platelet volume and moderate/severe periodontitis in adult persons who inhabit the U.S. METHODS: We screened 6,809 people from the National Health and Nutrition Examination Survey (NHANES 2009-2012). Mean platelet volume was measured in the Mobile Examination Centers (MECs) using the Beckman Coulter analyzer. The category of periodontitis was defined by the CDC/AAP using clinical periodontal parameters. Multiple logistic regression models were employed to examine the distribution for covariate differences across the various independent groups. Four models were employed to examine the relationship between mean platelet volume level and periodontitis. Smoothed curve fitting was utilized to confirm the linearity of the relationships. To determine the impact of factors on the connection between MPV and periodontitis, subgroup analysis and interaction testing were utilized. RESULTS: Results from the multiple logistic regression analysis indicate a significant association between moderate/severe periodontitis and the mean platelet level, even after considering any potential confounding variables (OR = 1.090, 95% CI: 1.019-1.166, P-value = 0.01211). Additionally, those in the upper tertile of mean platelet volume levels had a 21.6% higher probability of developing periodontitis when compared with those in the least tertile of mean platelet levels (OR = 1.216, 95% CI:1.052-1.406, P-value = 0.00816). Moreover, it showed a positive correlation between mean platelet volume (MPV) and moderate/severe periodontitis. Subgroup analyses indicated a positive association between the level of mean platelet volume and moderate/severe periodontitis among individuals who were under 60 years of age, had low income, were obese, never smoked, were heavy drinkers, had hypertension, and had no cardiovascular disease (p < 0.05). However, none of the subgroups exhibited significant interactions (p for interaction > 0.05). CONCLUSION: A correlation has been found between mean platelet volume levels and periodontal disease in individuals residing in the United States.


Assuntos
Volume Plaquetário Médio , Periodontite , Adulto , Humanos , Estados Unidos , Estudos Transversais , Inquéritos Nutricionais , Plaquetas
8.
Exp Cell Res ; 438(1): 114037, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38631545

RESUMO

Anoikis plays a crucial role in the progression, prognosis, and immune response of lung adenocarcinoma (LUAD). However, its specific impact on LUAD remains unclear. In this study, we investigated the intricate interplay of nesting apoptotic factors in LUAD. By analyzing nine key nesting apoptotic factors, we categorized LUAD patients into two distinct clusters. Further examination of immune cell profiles revealed that Cluster A exhibited greater infiltration of innate immune cells than did Cluster B. Additionally, we identified two genes closely associated with prognosis and developed a predictive model to differentiate patients based on molecular clusters. Our findings suggest that the loss of specific anoikis-related genes could significantly influence the prognosis, tumor microenvironment, and clinical features of LUAD patients. Furthermore, we validated the expression and functional roles of two pivotal prognostic genes, solute carrier family 2 member 1 (SLC2A1) and sphingosine kinase 1 (SPHK1), in regulating tumor cell viability, migration, apoptosis, and anoikis. These results offer valuable insights for future mechanistic investigations. In conclusion, this study provides new avenues for advancing our understanding of LUAD, improving prognostic assessments, and developing more effective immunotherapy strategies.

9.
Angew Chem Int Ed Engl ; : e202400382, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619863

RESUMO

Lithium-ion batteries, essential for electronics and electric vehicles, predominantly use cathodes made from critical materials like cobalt. Sulfur-based cathodes, offering a high theoretical capacity of 1675 mAh g-1 and environmental advantages due to sulfur's abundance and lower toxicity, present a more sustainable alternative. However, state-of-the-art sulfur-based electrodes do not reach the theoretical capacities, mainly because conventional electrode production relies on mixing of components into weakly coordinated slurries. Consequently, sulfur's mobility leads to battery degradation - an effect known as the "sulfur-shuttle". This study introduces a solution by developing a microporous, covalently-bonded, imine-based polymer network grown in-situ around sulfur particles on the current collector. The polymer network (i) enables selective transport of electrolyte and Li-ions through pores of defined size, and (ii) acts as a robust host to retain the active component of the electrode (sulfur species). The resulting cathode has superior rate performance from 0.1 C (1360 mAh g-1) to 3 C (807 mAh g-1). Demonstrating a high-performance, sustainable sulfur cathode produced via a simple one-pot process, our research underlines the potential of microporous polymers in addressing sulfur diffusion issues, paving the way for sulfur electrodes as viable alternatives to traditional metal-based cathodes.

10.
Planta ; 259(5): 109, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558186

RESUMO

MAIN CONCLUSION: Six methyltransferase genes affecting tomato fruit ripening were identified through genome-wide screening, VIGS assay, and expression pattern analysis. The data provide the basis for understanding new mechanisms of methyltransferases. Fruit ripening is a critical stage for the formation of edible quality and seed maturation, which is finely modulated by kinds of factors, including genetic regulators, hormones, external signals, etc. Methyltransferases (MTases), important genetic regulators, play vital roles in plant development through epigenetic regulation, post-translational modification, or other mechanisms. However, the regulatory functions of numerous MTases except DNA methylation in fruit ripening remain limited so far. Here, six MTases, which act on different types of substrates, were identified to affect tomato fruit ripening. First, 35 MTase genes with relatively high expression at breaker (Br) stage of tomato fruit were screened from the tomato MTase gene database encompassing 421 genes totally. Thereafter, six MTase genes were identified as potential regulators of fruit ripening via virus-induced gene silencing (VIGS), including four genes with a positive regulatory role and two genes with a negative regulatory role, respectively. The expression of these six MTase genes exhibited diverse patterns during the fruit ripening process, and responded to various external ripening-related factors, including ethylene, 1-methylcyclopropene (1-MCP), temperature, and light exposure. These results help to further elaborate the biological mechanisms of MTase genes in tomato fruit ripening and enrich the understanding of the regulatory mechanisms of fruit ripening involving MTases, despite of DNA MTases.


Assuntos
Frutas , Solanum lycopersicum , Frutas/metabolismo , Solanum lycopersicum/genética , Metiltransferases/genética , Metiltransferases/metabolismo , Epigênese Genética , Etilenos/metabolismo , Inativação Gênica , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
11.
Cereb Cortex ; 34(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38602744

RESUMO

Although previous studies have explored the associations of white matter hyperintensity with psychiatric disorders, the sample size is small and the conclusions are inconsistent. The present study aimed to further systematically explore the association in a larger sample. All data were extracted from the UK Biobank. First, general linear regression models and logistic regression models were used to assess the association between white matter hyperintensity volume and anxiety/depression. White matter hyperintensity has been classified into periventricular white matter hyperintensity and deep white matter hyperintensity. Anxiety was determined by General Anxiety Disorder-7 score (n = 17,221) and self-reported anxiety (n = 15,333), depression was determined by Patient Health Questionnaire-9 score (n = 17,175), and self-reported depression (n = 14,519). Moreover, we employed Cox proportional hazard models to explore the association between white matter hyperintensity volume and anxiety/depression. The covariates included in fully adjusted model are age, gender, body mass index, Townsend deprivation index, healthy physical activity, cigarette consumption, alcohol consumption, educational attainment, diabetes, hypertension, and coronary heart disease. The results of the fully adjusted model showed that white matter hyperintensity volume was significantly associated with General Anxiety Disorder-7 score (periventricular white matter hyperintensity: ß = 0.152, deep white matter hyperintensity: ß = 0.094) and Patient Health Questionnaire-9 score (periventricular white matter hyperintensity: ß = 0.168). Logistic regression analysis results indicated that periventricular white matter hyperintensity volume (odds ratio = 1.153) was significantly associated with self-reported anxiety. After applying the Cox proportional hazard models, we found that larger white matter hyperintensity volume was associated with increased risk of depression (periventricular white matter hyperintensity: hazard ratio = 1.589, deep white matter hyperintensity: hazard ratio = 1.200), but not anxiety. In summary, our findings support a positive association between white matter hyperintensity volume and depression.


Assuntos
Depressão , Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Transtornos de Ansiedade/diagnóstico por imagem , Transtornos de Ansiedade/epidemiologia , Ansiedade
12.
J Cell Mol Med ; 28(8): e18341, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38647235

RESUMO

Liver metastasis (LM) is an important factor leading to colorectal cancer (CRC) mortality. However, the effect of T-cell exhaustion on LM in CRC is unclear. Single-cell sequencing data derived from the Gene Expression Omnibus database. Data were normalized using the Seurat package and subsequently clustered and annotated into different cell clusters. The differentiation trajectories of epithelial cells and T cells were characterized based on pseudo-time analysis. Single-sample gene set enrichment analysis (ssGSEA) was used to calculate enrichment scores for different cell clusters and to identify enriched biological pathways. Finally, cell communication analysis was performed. Nine cell subpopulations were identified from CRC samples with LM. The proportion of T cells increased in LM. T cells can be subdivided into NK/T cells, regulatory T cells (Treg) and exhausted T cells (Tex). In LM, cell adhesion and proliferation activity of Tex were promoted. Epithelial cells can be categorized into six subpopulations. The transformation of primary CRC into LM involved two evolutionary branches of Tex cells. Epithelial cells two were at the beginning of the trajectory in CRC but at the end of the trajectory in CRC with LM. The receptor ligands CEACAM5 and ADGRE5-CD55 played critical roles in the interactions between Tex and Treg cell-epithelial cell, which may promote the epithelial-mesenchymal transition process in CRC. Tex cells are able to promote the process of LM in CRC, which in turn promotes tumour development. This provides a new perspective on the treatment and diagnosis of CRC.

13.
Front Neurosci ; 18: 1388748, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38650617

RESUMO

Background: There is evidence of an association between the gut microbiota and progression of stroke. However, the relationship between gut microbial metabolites, specifically bile acids (BAs), and post-ischemic stroke disability and poor functional outcomes remains unexplored. Methods: Patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) in the Third China National Stroke Registry were grouped according to total bile acid (TBA) quartile on admission. Association of TBA with disability and poor functional outcomes were evaluated using logistic regression models and restricted cubic splines. Results: Data for 9,536 patients were included. After adjusting for confounders, the risks of disability and poor functional outcomes were significantly lower in the highest TBA quartile than in the lowest TBA quartile at the 3-month follow-up, with respective odds ratios (ORs) of 0.65 (95% confidence interval [CI] 0.55-0.78; p < 0.001) and 0.66 (95% CI 0.55-0.78, p < 0.001). Each standard deviation increase in the TBA level reduced the risks of disability and poor functioning outcomes by 10% (adjusted ORs 0.9 [95% CI 0.83-0.98; p = 0.01] and 0.9 [95% CI 0.83-0.97; p < 0.001], respectively). This association remained similar at the 1-year follow-up. After stratification by TOAST subtype, the risk of disability or a poor functional outcome in patients with the large-artery atherosclerosis or "other" subtype was significantly lower in the highest quartile than in the lowest quartile (p < 0.05). Conclusion: Serum TBA is an independent risk factor for disability and poor functional outcomes after AIS or TIA, and exerts a protective effects on brain.

14.
Ying Yong Sheng Tai Xue Bao ; 35(3): 615-621, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38646748

RESUMO

The aim of this study was to reveal the stoichiometric characteristics of carbon, nitrogen and phosphorus in rhizosphere and non-rhizosphere soils of Pinus sylvestris var. mongolica in the Hulunbuir desert. We investigated the contents and stoichiometry of organic carbon, total nitrogen, and total phosphorus contents of rhizosphere and non-rhizosphere soils across different stand ages (28, 37 and 46 a) of P. sylvestris var. mongolica plantations, with P. sylvestris var. mongolica natural forest as the control. We analyzed the correlation between soils properties and soil stoichiometry. The results showed that rhizosphere effect significantly affected soil N:P, and stand age significantly affected soil organic carbon content in P. sylvestris var. mongolica plantation. Soil organic carbon content in plantation was significantly lower than that in natural forest. Soil organic carbon and total nitrogen contents of plantations in both rhizosphere and non-rhizosphere soils firstly decreased and then increased with increasing stand age, while total phosphorus firstly increased and then decreased in rhizosphere soils, and firstly decreased and then increased in non-rhizosphere soils. There was significant positive correlations between C:N and C:P in rhizosphere soils but not in non-rhizosphere soils, suggesting that higher synergistic rhizosphere soil N and P limitation. The mean N:P values of rhizosphere and non-rhizosphere soils were 4.98 and 8.40, respectively, indicating that the growth of P. sylvestris var. mongolica was restricted by soil N and the rhizosphere soils were more N-restricted. The C:N:P stoichiometry of rhizosphere and non-rhizosphere soils were significantly influenced by soil properties, with available phosphorus being the most important driver. The growth of P. sylvestris var. mongolica was limited by N in the Hulunbuir desert, and root system played an obvious role in enriching and maintaining soil nutrients. It was recommended that soil nitrogen should be supplemented appropriately during the growth stage of P. sylvestris var. mongolica plantation, and phosphorus should be supplemented appropriately according to the synergistic nature of nitrogen and phosphorus limitation.


Assuntos
Carbono , Nitrogênio , Fósforo , Pinus sylvestris , Rizosfera , Solo , Fósforo/análise , Nitrogênio/análise , Solo/química , Carbono/análise , Pinus sylvestris/crescimento & desenvolvimento , Florestas , China , Raízes de Plantas/metabolismo , Raízes de Plantas/química , Raízes de Plantas/crescimento & desenvolvimento
16.
Infect Drug Resist ; 17: 953-960, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495623

RESUMO

Background: The population with latent tuberculosis infection (LTBI) represents a potential pool of patients with active tuberculosis (ATB). T-SPOT.TB is an important test tool for screening LTBI. Owing to the large population of LTBI patients in China, it is necessary to identify a high-risk group for LTBI and enlarge tuberculosis preventive treatment (TPT) to reduce the incidence of ATB. Methods: Hospitalized patients with positive T-SPOT.TB results were recruited from January 2013 to December 2016. Patients with ATB were excluded. Basic information was collected and the development of ATBs was examined during follow-up. The life-table method was used to calculate cumulative incidence rates. Potential risk factors were analyzed through Cox regression analysis. Results: A total of 1680 patients with LTBI were recruited in the follow-up cohort, and 377 (22.44%) patients dropped out. With a median follow-up time of 81 months [interquartile range (IQR):61-93], 19 of 1303 patients with LTBI developed ATB. The 1-year incidence of ATB was 614 per 100,000 individuals [95%confidence interval (95% CI):584-644]. Over 5-year period, the cumulative incidence of ATB was 1496 per 100,000 [95% CI:1430-1570], and the incidence density was 240 per 100,000 person-years[95% CI:144-375]. In the Cox regression model, exposure of pulmonary tuberculosis (PTB) [adjusted hazard ratio (aHR)=10.557, 95% CI:2.273-49.031], maximum daily dosage of glucocorticoids (GCs)≥ 50 mg/d (aHR=2.948, 95% CI:1.122-7.748), leflunomide (LEF) treatment (aHR=8.572, 95% CI:2.222 -33.070), anemia (aHR=2.565, 95% CI:1.015-6.479) and T-SPOT.TB level≥300SFCs/106 PBMCs (aHR=4.195, 95% CI:1.365-12.892) were independent risk factors for ATB development in LTBI patients. Conclusion: The incidence of ATB is significantly higher in hospitalized patients with LTBI than in the general population. The exposure history of PTB, maximum daily dosage of GCs≥ 50 mg/day, LEF treatment, anemia, and T-SPOT.TB level≥300SFCs/106PBMCs, were the risk factors of tuberculosis reactivation. Hospitalized LTBI patients with the above factors may need TPT.

17.
Comput Struct Biotechnol J ; 23: 1144-1153, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38510975

RESUMO

N6 adenosine methylation (m6A), one of the most prevalent internal modifications on mammalian RNAs, regulates RNA transcription, stabilization, and splicing. Growing evidence has focused on the functional role of m6A regulators on acute myeloid leukemia (AML). However, the global m6A levels after azacytidine (AZA) plus venetoclax (VEN) treatment in AML patients remain unclear. In our present study, bone marrow (BM) sample pairs (including pre-treatment [AML] and post-treatment [complete remission (CR)] samples) were harvested from three AML patients who had achieved CR after AZA plus VEN treatment for Nanopore direct RNA sequencing. Notably, the amount of m6A sites and the m6A levels in CR BMs was significantly lower than those in the AML BMs. Such a significant reduction in the m6A levels was also detected in AZA-treated HL-60 cells. Thirteen genes with decreased m6A and expression levels were identified, among which three genes (HPRT1, SNRPC, and ANP32B) were closely related to the prognosis of AML. Finally, we speculated the mechanism via which m6A modifications affected the mRNA stability of these three genes. In conclusion, we illustrated for the first time the global landscape of m6A levels in AZA plus VEN treated AML (CR) patients and revealed that AZA had a significant demethylation effect at the RNA level in AML patients. In addition, we identified new biomarkers for AZA plus VEN-treated AML via Nanopore sequencing technology in RNA epigenetics.

18.
Cancer Res ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38536119

RESUMO

The widespread use of androgen receptor (AR) signaling inhibitors has led to an increased incidence of AR-negative castration-resistant prostate cancer (CRPC), limiting effective treatment and patient survival. A more comprehensive understanding of the molecular mechanisms supporting AR-negative CRPC could reveal therapeutic vulnerabilities to improve treatment. This study showed that the transcription factor nuclear factor I/B (NFIB) was upregulated in AR-negative CRPC patient tumors and cell lines and was positively associated with an epithelial-to-mesenchymal transition (EMT) phenotype. Loss of NFIB inhibited EMT and reduced migration of CRPC cells. NFIB directly bound to gene promoters and regulated the transcription of EMT-related factors E-cadherin and vimentin, independently of other typical EMT-related transcriptional factors. In vivo data further supported the positive role of NFIB in the metastasis of AR-negative CRPC cells. Moreover, N6-methyladenosine (m6A) modification induced NFIB upregulation in AR-negative CRPC. Mechanistically, the m6A levels of mRNA, including NFIB and its E3 ubiquitin ligase TRIM8, were increased in AR-negative CRPC cells. Elevated m6A methylation of NFIB mRNA recruited YTHDF2 to increase mRNA stability and protein expression. Inversely, the m6A modification of TRIM8 mRNA, induced by ALKBH5 downregulation, decreased its translation and expression, which further promoted NFIB protein stability. Overall, this study reveals that upregulation of NFIB, mediated by m6A modification, triggers EMT and metastasis in AR-negative CRPC. Targeting the m6A/NFIB axis is a potential prevention and treatment strategy for AR-negative CRPC metastasis.

19.
Sensors (Basel) ; 24(6)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38544067

RESUMO

Perception plays a crucial role in ensuring the safety and reliability of autonomous driving systems. However, the recognition and localization of small objects in complex scenarios still pose challenges. In this paper, we propose a point cloud object detection method based on dynamic sparse voxelization to enhance the detection performance of small objects. This method employs a specialized point cloud encoding network to learn and generate pseudo-images from point cloud features. The feature extraction part uses sliding windows and transformer-based methods. Furthermore, multi-scale feature fusion is performed to enhance the granularity of small object information. In this experiment, the term "small object" refers to objects such as cyclists and pedestrians, which have fewer pixels compared to vehicles with more pixels, as well as objects of poorer quality in terms of detection. The experimental results demonstrate that, compared to the PointPillars algorithm and other related algorithms on the KITTI public dataset, the proposed algorithm exhibits improved detection accuracy for cyclist and pedestrian target objects. In particular, there is notable improvement in the detection accuracy of objects in the moderate and hard quality categories, with an overall average increase in accuracy of about 5%.

20.
Front Med (Lausanne) ; 11: 1339573, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487022

RESUMO

Bone defects resulting from severe trauma, tumors, inflammation, and other factors are increasingly prevalent. Stem cell-based therapies have emerged as a promising alternative. Dental pulp stem cells (DPSCs), sourced from dental pulp, have garnered significant attention owing to their ready accessibility and minimal collection-associated risks. Ongoing investigations into DPSCs have revealed their potential to undergo osteogenic differentiation and their capacity to secrete a diverse array of ontogenetic components, such as extracellular vesicles and cell lysates. This comprehensive review article aims to provide an in-depth analysis of DPSCs and their secretory components, emphasizing extraction techniques and utilization while elucidating the intricate mechanisms governing bone regeneration. Furthermore, we explore the merits and demerits of cell and cell-free therapeutic modalities, as well as discuss the potential prospects, opportunities, and inherent challenges associated with DPSC therapy and cell-free therapies in the context of bone regeneration.

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