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1.
World J Gastrointest Oncol ; 16(4): 1421-1436, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38660653

RESUMO

BACKGROUND: Metabolic reprogramming plays a key role in cancer progression and clinical outcomes; however, the patterns and primary regulators of metabolic reprogramming in colorectal cancer (CRC) are not well understood. AIM: To explore the role of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in promoting progression of CRC. METHODS: We evaluated the expression and function of dysregulated and survival-related metabolic genes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Consensus clustering was used to cluster CRC based on dysregulated metabolic genes. A prediction model was constructed based on survival-related metabolic genes. Sphere formation, migration, invasion, proliferation, apoptosis and clone formation was used to evaluate the biological function of NOX4 in CRC. mRNA sequencing was utilized to explore the alterations of gene expression NOX4 over-expression tumor cells. In vivo subcutaneous and lung metastasis mouse tumor model was used to explore the effect of NOX4 on tumor growth. RESULTS: We comprehensively analyzed 3341 metabolic genes in CRC and identified three clusters based on dysregulated metabolic genes. Among these genes, NOX4 was highly expressed in tumor tissues and correlated with worse survival. In vitro, NOX4 overexpression induced clone formation, migration, invasion, and stemness in CRC cells. Furthermore, RNA-sequencing analysis revealed that NOX4 overexpression activated the mitogen-activated protein kinase-MEK1/2-ERK1/2 signaling pathway. Trametinib, a MEK1/2 inhibitor, abolished the NOX4-mediated tumor progression. In vivo, NOX4 overexpression promoted subcutaneous tumor growth and lung metastasis, whereas trametinib treatment can reversed the metastasis. CONCLUSION: Our study comprehensively analyzed metabolic gene expression and highlighted the importance of NOX4 in promoting CRC metastasis, suggesting that trametinib could be a potential therapeutic drugs of CRC clinical therapy targeting NOX4.

2.
Lab Invest ; 104(5): 102041, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38431116

RESUMO

A specific splicing isoform of RNASET2 is associated with worse oncologic outcomes in clear cell renal cell carcinoma (ccRCC). However, the interplay between wild-type RNASET2 and its splice variant and how this might contribute to the pathogenesis of ccRCC remains poorly understood. We sought to better understand the relationship of RNASET2 in the pathogenesis of ccRCC and the interplay with a pathogenic splicing isoform (RNASET2-SV) and the tumor immune microenvironment. Using data from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium, we correlated clinical variables to RNASET2 expression and the presence of a specific RNASET2-SV. Immunohistochemical staining with matched RNA sequencing of ccRCC patients was then utilized to understand the spatial relationships of RNASET2 with immune cells. Finally, in vitro studies were performed to demonstrate the oncogenic role of RNASET2 and highlight its potential mechanisms. RNASET2 gene expression is associated with higher grade tumors and worse overall survival in The Cancer Genome Atlas cohort. The presence of the RNASET2-SV was associated with increased expression of the wild-type RNASET2 protein and epigenetic modifications of the gene. Immunohistochemical staining revealed increased intracellular accumulation of RNASET2 in patients with increased RNA expression of RNASET2-SV. In vitro experiments reveal that this accumulation results in increased cell proliferation, potentially from altered metabolic pathways. RNASET2 exhibits a tumor-promoting role in the pathogenesis of ccRCC that is increased in the presence of a specific RNASET2-SV and associated with changes in the cellular localization of the protein.

3.
Nat Commun ; 15(1): 1148, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326303

RESUMO

Melanoma incidence and mortality rates are historically higher for men than women. Although emerging studies have highlighted tumorigenic roles for the male sex hormone androgen and its receptor (AR) in melanoma, cellular and molecular mechanisms underlying these sex-associated discrepancies are poorly defined. Here, we delineate a previously undisclosed mechanism by which androgen-activated AR transcriptionally upregulates fucosyltransferase 4 (FUT4) expression, which drives melanoma invasiveness by interfering with adherens junctions (AJs). Global phosphoproteomic and fucoproteomic profiling, coupled with in vitro and in vivo functional validation, further reveal that AR-induced FUT4 fucosylates L1 cell adhesion molecule (L1CAM), which is required for FUT4-increased metastatic capacity. Tumor microarray and gene expression analyses demonstrate that AR-FUT4-L1CAM-AJs signaling correlates with pathological staging in melanoma patients. By delineating key androgen-triggered signaling that enhances metastatic aggressiveness, our findings help explain sex-associated clinical outcome disparities and highlight AR/FUT4 and its effectors as potential prognostic biomarkers and therapeutic targets in melanoma.


Assuntos
Melanoma , Molécula L1 de Adesão de Célula Nervosa , Humanos , Masculino , Feminino , Melanoma/metabolismo , Androgênios , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Antígenos CD15/metabolismo , Glicosilação , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Linhagem Celular Tumoral , Fucosiltransferases/genética , Fucosiltransferases/metabolismo
4.
Int J Med Sci ; 21(3): 496-507, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38250606

RESUMO

Background: Pyroptosis is a programmed death mode of inflammatory cells, which is closely related to tumor progression and tumor immunity. Clear cell renal cell carcinoma (ccRCC) is the major pathological type of renal cell carcinoma (RCC) with poor prognosis. Many theories have tried to clarify the mechanism in the development of ccRCC, but the role of pyroptosis in ccRCC has not been well described. The main purpose of this study is to explore the role of pyroptosis in ccRCC and establish a novel prognosis prediction model of pyroptosis-related molecular signatures for ccRCC. Methods: In the present study, we made a systematical analysis of the association between ccRCC RNA transcriptome sequencing data from The Cancer Genome Atlas (TCGA) database [which included 529 ccRCC patients who were randomized in a training cohort (n=265) and an internal validation cohort (n=264)] and 40 pyroptosis-related genes (PRGs), from which four genes (CASP9, GSDME, IL1B and TIRAP) were selected to construct a molecular prediction model of PRGs for ccRCC. In addition, a cohort of 114 ccRCC patients from Shanghai Eastern Hepatobiliary Surgery Hospital (EHSH) was used as external data to verify the effectiveness of the model by immunohistochemistry. Moreover, the biological functions of the four PRGs were also verified in ccRCC 786-O and 769-P cells by Western blot (WB), CCK-8 cell proliferation, and Transwell invasion assays. Results: The model was able to differentiate high-risk patients from low-risk patients, and this differentiation was consistent with their clinical survival outcomes. In addition, the four PRGs also affected the ability of cell proliferation and invasion in ccRCC. Conclusion: The prediction model of pyroptosis-related molecular markers developed in this study may prove to be a novel understanding for ccRCC.


Assuntos
Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Piroptose/genética , China , Prognóstico , Neoplasias Renais/genética
5.
J Biomol Struct Dyn ; : 1-18, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38173169

RESUMO

Sunitinib remains the preferred systemic treatment option for specific patients with advanced RCC who are ineligible for immune therapy. However, it's essential to recognize that Sunitinib fails to elicit a favourable response in all patients. Moreover, most patients eventually develop resistance to Sunitinib. Therefore, identifying new targets associated with Sunitinib resistance is crucial. Utilizing multiple datasets from public cohorts, we conducted an exhaustive analysis and identified a total of 8 microRNAs and 112 mRNAs displaying significant expression differences between Sunitinib responsive and resistant groups. A particular set of six genes, specifically NIPSNAP1, STK40, SDC4, NEU1, TBC1D9, and PLAUR, were identified as highly significant via WGCNA. To delve deeper into the resistance mechanisms, we performed additional investigations using cell, molecular, and flow cytometry tests. These studies confirmed PLAUR's pivotal role in fostering Sunitinib resistance, both in vitro and in vivo. Our findings suggest that PLAUR could be a promising therapeutic target across various cancer types. In conclusion, this investigation not only uncovers vital genes and microRNAs associated with Sunitinib resistance in RCC but also introduces PLAUR as a prospective therapeutic target for diverse cancers. The outcomes contribute to advancing personalized healthcare and developing superior therapeutic strategies.Communicated by Ramaswamy H. Sarma.

6.
Biol Trace Elem Res ; 202(2): 597-614, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37148403

RESUMO

A two-generation reproductive toxicity study was performed to evaluate the effects of cerium nitrate on the development of the parent, offspring, and third generation of Sprague-Dawley (SD) rats. A total of 240 SD rats (30 rats/sex/group) were randomly divided into four dosage groups according to body weight: 0 mg/kg, 30 mg/kg, 90 mg/kg, and 270 mg/kg. The rats were administered different dosages of cerium nitrate by oral gavage. There were no observed changes related to cerium nitrate in body weight, food consumption, sperm survival rate, motility, mating rate, conception rate, abortion rate, uterine plus fetal weight, uterine weight, corpus luteum number, implantation rate, live fetus number (rate), stillbirth number (rate), absorbed fetus number (rate), appearance, visceral, and skeletal in rats of each generation dosage group. In addition, the pathological findings showed no significant lesions associated with cerium nitrate toxicity in all tissues and organs, including reproductive organs. In conclusion, the present study showed that long-term oral gavage of cerium nitrate at 30 mg/kg, 90 mg/kg, and 270 mg/kg had no significant effect on reproduction and the developmental ability of their offspring in rats. The no-observed-adverse-effect level (NOAEL) of cerium nitrate in SD rats was higher than 270 mg/kg.


Assuntos
Reprodução , Sêmen , Gravidez , Feminino , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Administração Oral , Peso Corporal
7.
medRxiv ; 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37904926

RESUMO

Background: Currently there are no biomarkers to identify resistance to androgen-deprivation therapy (ADT) in men with hormone-naive prostate cancer. 5-hydroxymethylcytosines (5hmC) in the gene body are associated with gene activation and are critical for epigenomic regulation of cancer progression. Objective: To evaluate whether 5hmC signature in cell-free DNA (cfDNA) predicts early ADT resistance. Design Setting and Participants: Serial plasma samples from 55 prostate cancer patients receiving ADT were collected at three timepoints including baseline (prior to initiating ADT, N=55), 3-month (after initiating ADT, N=55), and disease progression (N=15) within 24 months or 24-month if no progression was detected (N=14). 20 of the 55 patients showed disease progression during the 24-month follow-up. The remaining 35 patients showed no progression in the same follow-up period. Outcome Measurements and Statistical Analysis: cfDNA (5-10ng) was used for selective chemical labeling (hMe-Seal) sequencing to map 5hmC abundance across the genome. Read counts in gene bodies were normalized with DESeq2. Differential methylation and gene set enrichment analyses were performed to identify the 5hmC-enriched genes and biological processes that were associated with disease progression. Kaplan-Meir analysis was utilized to determine the association of 5hmC signatures with progression-free survival. Results and Limitations: 5hmC-sequencing generated an average of 18.6 (range 6.03 to 42.43) million reads per sample with 98% (95-99%) mappable rate. Baseline sample comparisons identified significant 5hmC difference in 1,642 of 23,433 genes between 20 patients with progression and 35 patients without progression (false discovery rate, FDR<0.1). Patients with progression showed significant enrichments in multiple hallmark gene sets with androgen responses as the top enriched gene set (FDR=1.19E-13). Interestingly, this enrichment was driven by a subgroup of patients with disease progression featuring a significant 5hmC hypermethylation of the gene sets involving AR, FOXA1 and GRHL2. To quantify overall activities of these gene sets, we developed a gene set activity score algorithm using a mean value of log2 ratios of gene read counts in an entire gene set. We found that the activity scores in these gene sets were significantly higher in this subgroup of patients with progression than in the remaining patients regardless of the progression status. Furthermore, the high activity scores in these gene sets were associated with poor progression-free survival (p <0.05). Longitudinal analysis showed that activity scores in this subgroup with progression were significantly reduced after 3-month ADT but returned to high levels when the disease was progressed. Conclusions: 5hmC-sequencing in cfDNA identified a subgroup of prostate cancer patients with preexisting activation (5hmC hypermethylation) of gene sets involving AR, FOXA1 and GRHL2 before initiating ADT. Activity scores in these gene sets may serve as sensitive biomarkers to determine treatment resistance, monitor disease progression and potentially identify patients who would benefit from upfront treatment intensification. More studies are needed to validate this initial finding. Patient summary: There are no clinical tests to identify prostate cancer patients who will develop early resistance to androgen deprivation therapy within 24 months. In this study, we evaluated cell-free DNA epigenomic modification in blood and identified significant enrichment of 5-hydroxymethylation in androgen response genes in a subgroup of patients with treatment resistance. High level 5-hydroxylmethylation in these genes may serve as a discriminative biomarker to diagnose patients who are likely to experience early failure during androgen deprivation therapy.

8.
Nanomaterials (Basel) ; 13(17)2023 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-37686939

RESUMO

Sustainable and high-performance energy storage materials are crucial to address global energy and environmental challenges. In this study, Spirulina platensis was used as the carbon and nitrogen source, and Spirulina-based nanoporous biochar (SNPB) was synthesized through chemical activation using KOH as the activating agent in N2 atmosphere. SNPB-800-4 was characterized by N2 adsorption-desorption and XPS, showing a high specific surface area (2923.7 m2 g-1) and abundant heteroatomic oxygen (13.78%) and nitrogen (2.55%). SNPB-800-4 demonstrated an exceptional capacitance of 348 F g-1 at a current density of 1 A g-1 and a remarkable capacitance retention of 94.14% after 10,000 cycles at a current density of 10 A g-1 in 6 M KOH. Notably, symmetric supercapacitors SNPB-800-4//SNPB-800-4 achieved the maximum energy and power densities of 17.99 Wh kg-1 and 162.48 W kg-1, respectively, at a current density of 0.5 A g-1, and still maintained 2.66 Wh kg-1 when the power density was increased to 9685.08 W kg-1 at a current density of 30 A g-1. This work provides an easily scalable and straightforward way to convert waste algae biomass into in situ N, O-dually doped biochar for ultra-high-power supercapacitors.

9.
RSC Adv ; 13(37): 25877-25887, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37664215

RESUMO

How to efficiently treat municipal solid waste (MSW) has become one of the critical solutions in response to the call for "carbon neutrality". Here, the waste polypropylene nonwoven fabric of waste diapers was converted into hierarchical nanoporous biochar (HPBC) through pre-carbonization and activation processes as an ideal precursor for supercapacitors (SCs) with excellent performance. The prepared HPBC-750-4 with an ultrahigh specific surface area (3838.04 m2 g-1) and abundant heteroatomic oxygen (13.25%) and nitrogen (1.16%) codoped porous biochar structure. Given its structural advantages, HPBC-750-4 achieved a specific capacitance of 340.9 F g-1 at a current density of 1 A g-1 in a three-electrode system. Its capacitance retention rate was above 99.2% after 10 000 cycles at a current density of 10 A g-1, which indicated an excellent rate capability and long-term cycling stability. Furthermore, the HPBC-750-4//HPBC-750-4 symmetric SC exhibited a superb energy density of 10.02 W h kg-1 with a power density of 96.15 W kg-1 in a 6 M KOH electrolyte. This work not only demonstrates the enormous potential of waste polypropylene nonwoven fabric in the SC industry but also provides an economically feasible means of managing MSW.

10.
Molecules ; 28(18)2023 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-37764320

RESUMO

The conversion of nitrogen-oxygen-rich biomass wastes into heteroatomic co-doped nanostructured carbons used as energy storage materials has received widespread attention. In this study, an in situ nitrogen-oxygen co-doped porous carbon was prepared for supercapacitor applications via a two-step method of pre-carbonization and pyrolytic activation using mixed egg yolk/white and rice waste. The optimal sample (YPAC-1) was found to have a 3D honeycomb structure composed of abundant micropores and mesopores with a high specific surface area of 1572.1 m2 g-1, which provided abundant storage space and a wide transport path for electrolyte ions. Notably, the specific capacitance of the constructed three-electrode system was as high as 446.22 F g-1 at a current density of 1 A g-1 and remained above 50% at 10 A g-1. The capacitance retention was 82.26% after up to 10,000 cycles. The symmetrical capacitor based on YPAC-1 with a two-electrode structure exhibited an energy density of 8.3 Wh kg-1 when the power density was 136 W kg-1. These results indicate that porous carbon materials prepared from mixed protein and carbohydrate waste have promising applications in the field of supercapacitors.

11.
RSC Adv ; 13(34): 24140-24149, 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37577085

RESUMO

With the widespread use of antibiotics, the safe utilization of waste antibiotic fermentation residues has become an urgent issue to be resolved. In this study, in situ N, O co-doped porous carbon was prepared using fresh oxytetracycline fermentation residue under the mild activation of the green activator K2CO3. The optimal sample exhibited a 3D grid carbon skeleton structure, excellent specific surface area (SBET = 948 m2 g-1), and high nitrogen and oxygen content (N = 3.42 wt%, O = 14.86 wt%). Benefiting from its developed morphology, this sample demonstrated excellent electrochemical performance with a high specific capacitance of 310 F g-1 at a current density of 0.5 A g-1 in the three-electrode system. Moreover, it exhibited superior cycling stability with only a 5.32% loss of capacity after 10 000 cycles in 6 M KOH aqueous electrolyte. Furthermore, the symmetric supercapacitor prepared from it exhibited a maximum energy density of 7.2 W h kg-1 at a power density of 124.9 W kg-1, demonstrating its promising application prospects. This study provided a green and facile process for the sustainable and harmless treatment of antibiotic fermentation residues.

12.
Cancer Cell Int ; 23(1): 186, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37649034

RESUMO

BACKGROUND: Renal cell carcinoma (RCC) is a hypermetabolic disease. Abnormal up-regulation of glycolytic signaling promotes tumor growth, and glycolytic metabolism is closely related to immunotherapy of renal cancer. The aim of the present study was to determine whether and how the glycolysis-related biomarker TCIRG1 affects aerobic glycolysis, the tumor microenvironment (TME) and malignant progression of clear cell renal cell carcinoma (ccRCC). METHODS: Based on The Cancer Genome Atlas (TCGA, n = 533) and the glycolysis-related gene set from MSigDB, we identified the glycolysis-related gene TCIRG1 by bioinformatics analysis, analyzed its immunological properties in ccRCC and observed how it affected the biological function and glycolytic metabolism using online databases such as TIMER 2.0, UALCAN, LinkedOmics and in vitro experiments. RESULTS: It was found that the expression of TCIRG1, was significantly increased in ccRCC tissue, and that high TCIRG1 expression was associated with poor overall survival (OS) and short progression-free interval (PFI). In addition, TCIRG1 expression was highly correlated with the infiltration immune cells, especially CD4+T cell Th1, CD8+T cell, NK cell, and M1 macrophage, and positively correlated with PDCD1, CTLA4 and other immunoinhibitors, CCL5, CXCR3 and other chemokines and chemokine receptors. More importantly, TCIRG1 may regulate aerobic glycolysis in ccRCC via the AKT/mTOR signaling pathway, thereby affecting the malignant progression of ccRCC cell lines. CONCLUSIONS: Our results demonstrate that the glycolysis-related biomarker TCIRG1 is a tumor-promoting factor by affecting aerobic glycolysis and tumor immune microenvironment in ccRCC, and this finding may provide a new idea for the treatment of ccRCC by combination of metabolic intervention and immunotherapy.

13.
Am J Hum Genet ; 110(8): 1289-1303, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37541187

RESUMO

Genome-wide association studies along with expression quantitative trait locus (eQTL) mapping have identified hundreds of single-nucleotide polymorphisms (SNPs) and their target genes in prostate cancer (PCa), yet functional characterization of these risk loci remains challenging. To screen for potential regulatory SNPs, we designed a CRISPRi library containing 9,133 guide RNAs (gRNAs) to cover 2,166 candidate SNP loci implicated in PCa and identified 117 SNPs that could regulate 90 genes for PCa cell growth advantage. Among these, rs60464856 was covered by multiple gRNAs significantly depleted in screening (FDR < 0.05). Pooled SNP association analysis in the PRACTICAL and FinnGen cohorts showed significantly higher PCa risk for the rs60464856 G allele (p value = 1.2 × 10-16 and 3.2 × 10-7, respectively). Subsequent eQTL analysis revealed that the G allele is associated with increased RUVBL1 expression in multiple datasets. Further CRISPRi and xCas9 base editing confirmed that the rs60464856 G allele leads to elevated RUVBL1 expression. Furthermore, SILAC-based proteomic analysis demonstrated allelic binding of cohesin subunits at the rs60464856 region, where the HiC dataset showed consistent chromatin interactions in prostate cell lines. RUVBL1 depletion inhibited PCa cell proliferation and tumor growth in a xenograft mouse model. Gene-set enrichment analysis suggested an association of RUVBL1 expression with cell-cycle-related pathways. Increased expression of RUVBL1 and activation of cell-cycle pathways were correlated with poor PCa survival in TCGA datasets. Our CRISPRi screening prioritized about one hundred regulatory SNPs essential for prostate cell proliferation. In combination with proteomics and functional studies, we characterized the mechanistic role of rs60464856 and RUVBL1 in PCa progression.


Assuntos
Próstata , Neoplasias da Próstata , Animais , Humanos , Masculino , Camundongos , Alelos , ATPases Associadas a Diversas Atividades Celulares/genética , Proteínas de Transporte/genética , DNA Helicases/genética , Detecção Precoce de Câncer , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único/genética , Próstata/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteômica
14.
Environ Pollut ; 333: 121972, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37295710

RESUMO

It is of great environmental benefit to rationally dispose of and utilize antibiotic fermentation residues. In this study, oxytetracycline fermentation residue was transformed into an in-situ nitrogen-doped nanoporous carbon material with high CO2 adsorption performance by low-temperature pyrolysis pre-carbonization coupled with pyrolytic activation. The results indicated the activation under mild conditions (600 °C, KOH/OC = 2) was able to increase micropores and reduce the loss of in-situ nitrogen content. The developed microporous structure was beneficial for the filling adsorption of CO2, and the in-situ nitrogen doping in a high oxygen-containing carbon framework also strengthened the electrostatic adsorption with CO2. The maximum CO2 adsorption reached 4.38 mmol g-1 and 6.40 mmol g-1 at 25 °C and 0 °C (1 bar), respectively, with high CO2/N2 selectivity (32/1) and excellent reusability (decreased by 4% after 5 cycles). This study demonstrates the good application potential of oxytetracycline fermentation residue as in-situ nitrogen-doped nanoporous carbon materials for CO2 capture.


Assuntos
Nanoporos , Oxitetraciclina , Carbono/química , Dióxido de Carbono/química , Nitrogênio/química , Antibacterianos , Fermentação
15.
Transl Androl Urol ; 12(4): 659-672, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37181236

RESUMO

Background: Clear cell renal cell carcinoma (ccRCC) is a highly heterogeneous tumor and is the most common subtype of renal cell carcinoma (RCC). Surgery is used to cure most early ccRCC, but the 5-year overall survival (OS) of ccRCC patients is far from satisfactory. Thus, new prognostic features and therapeutic targets for ccRCC need to be identified. Since complement factors can influence tumor development, we aimed to develop a model to predict the prognosis of ccRCC through complement-related genes. Methods: Differentially expressed genes were screened from an International Cancer Genome Consortium (ICGC) data set, and the genes associated with prognosis were screened by univariate regression and least absolute shrinkage and selection operator-Cox regression, and column line plots were generated using the rms R package to predict OS. The C-index was used to show the accuracy of the survival prediction and the prediction effects were verified using a data set from The Cancer Genome Atlas (TCGA). An immuno-infiltration analysis was performed with CIBERSORT analysis, and a drug sensitivity analysis was performed using the Gene Set Cancer Analysis (GSCA) (http://bioinfo.life.hust.edu.cn/GSCA/#/) database. Results: We identified 5 complement-related genes (i.e., A2M, APOBEC3G, COL4A2, DOCK4, and NOTCH4) for risk-score modeling to predict OS at 1, 2, 3, and 5 years, and the C-index of the prediction mode was 0.795. In addition, the model was successfully validated in TCGA data set. The CIBERSORT analysis showed that M1 macrophages were downregulated in the high-risk group. The GSCA database analysis showed that DOCK4, COL4A2, and A2M were positively correlated with the half maximal inhibitory concentration (IC50) of 10 drugs and small molecules, and COL4A2, NOTCH4, A2M, and APOBEC3G were negatively correlated with the IC50 of dozens of different drugs and small molecules. Conclusions: We developed and validated a survival prognostic model based on 5 complement-related genes for ccRCC. We also elucidated the relationship with tumor immune status and developed a new predictive tool for clinical purposes. In addition, our results showed that A2M, APOBEC3G, COL4A2, DOCK4, and NOTCH4 may be potential targets for the treatment of ccRCC in the future.

16.
Environ Pollut ; 330: 121681, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37087086

RESUMO

The effective removal of tetracycline antibiotics (TCs) from water is of great significance and remains a big challenge. In this work, a novel magnetized biochar (magnetic functionalized carbon microsphere, MF-CMS) was prepared by the coupling hydrothermal carbonization and pyrolysis activation of starch-rich rice waste using ZnCl2 and FeCl3 as activators. As the MF-CMS dose was 2.0 g/L, the initial concentration of TCs was 100 mg/L, the removal rates of tetracycline, doxycycline, oxytetracycline, and chlortetracycline were 96.02%, 96.10%, 96.52%, and 85.88%, respectively. The best modeled on pseudo second order, Langmuir adsorption model, and intraparticle diffusion kinetic models suggested that both chemisorption and physisorption occurred in all removal processes, in which chemisorption dominated. TCs were efficiently adsorbed through the combined effects of pore filling, electrostatic attraction, π-π interactions, and complexation reactions of surface functional groups (such as γ-Fe2O3 and FeOOH). The removal rates of TCs after five cycles approximately decreased by 20%. And the cycling and metal ion release experiments of MF-CMS indicated that MF-CMS had good reusability, stability, and safety. The estimated cost of preparing MF-CMS is 5.91 USD per kg, and 1 kg of MF-CMS (consuming 8 kg of waste rice) can approximately treat 0.55 tons of TCs wastewater. Overall, the magnetic biochar derived from starch-rich rice waste as an adsorbent has promising and effective for the removal of TCs from water, but also provides a new idea for the resourceful treatment of solid waste.


Assuntos
Oryza , Poluentes Químicos da Água , Água , Antibacterianos , Tetraciclina , Carvão Vegetal , Adsorção , Fenômenos Magnéticos , Cinética
17.
Sci Total Environ ; 883: 163590, 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37088389

RESUMO

The toxicological and pathological influences of polybrominated diphenyl ethers (PBDEs) on the animal central nervous system have attracted worldwide attention. However, their mechanism of action has not been completely elucidated. Given that retinoic acid (RA) and thyroid hormone (TH) signaling pathway are closely related to neurodevelopment, the crosstalk between the two signaling pathways at the levels of metabolite conversion, gene expression and ligand-receptor interaction after exposure to two representative PBDE congeners (BDE-47 and BDE-209) using zebrafish larvae, dual reporter gene assay, and docking simulation was studied. Our results clarified that BDE-47 could disrupt the transport and metabolism of retinoids, induce changes in expression of key genes, bind with the seven nuclear receptors, and activate RA signaling pathway. BDE-47 exhibited more effects on the indicators of the two signaling pathways than BDE-209. Furthermore, BDE-47 may disrupt TH signaling pathway by disrupting RA signaling pathway, indicating that RA signal is priorly influenced than TH signal. This work offered a new perspective to elucidate TH signal disruption mechanism induced by PBDEs from RA signaling pathway, which is of great significance to elucidate the health effects of PBDEs.


Assuntos
Éteres Difenil Halogenados , Peixe-Zebra , Animais , Éteres Difenil Halogenados/toxicidade , Éteres Difenil Halogenados/metabolismo , Peixe-Zebra/metabolismo , Tretinoína/toxicidade , Tretinoína/metabolismo , Hormônios Tireóideos/metabolismo , Transdução de Sinais
18.
Sci Rep ; 13(1): 6043, 2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-37055537

RESUMO

BeiDou Satellite-based Augmentation System (BDSBAS) has come into the trial operation stage since July, 2020. To evaluate the characteristic of the augmentation message in BDSBAS-B1C signal, the effectiveness of the message content was firstly analyzed, and then the validity of the broadcasting strategy was estimated. Finally, the accuracy of the user equivalent ranging error (UERE) and the single frequency positioning error with different correction parameters in BDSBAS-B1C message was evaluated. Based on the above analysis, the effectiveness of the augmentation message was preliminarily verified with the results showing that: (1) the BDSBAS-B1C message type, information content and update interval have basically met the international standard; (2) the accuracy of the UERE obtained with the augmentation message had an obvious improvement in contrast to that of the UERE obtained with the usual navigation message of the GPS satellites, and the ionospheric delay was one of the important factors which affected the accuracy of the UERE; (3) the positioning accuracy obtained with the augmentation message was also improved, and the improvement was more obvious in the service areas with high availability of the ionospheric parameters.

19.
Regul Toxicol Pharmacol ; 140: 105381, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36963718

RESUMO

In this study, the toxicity of ferric oxide nanoparticles (Fe2O3 NPs) administered through gavage to Sprague Dawley (SD) rats for 94 d, consecutively and the recovery after Fe2O3 NPs withdrawal for 30 d were evaluated. The vehicle control group, low-, medium-, and high-dose groups were administered with the vehicle (0.5% sodium carboxymethyl cellulose [CMC-Na]), 125, 250, and 500 mg/kg of Fe2O3 NPs, respectively, administered every morning for 94 d. There was no significant difference in the body weight, food intake, hematological, blood biochemical, and urine indices of SD rats in each administration group and the control group (P > 0.05). There was no significant difference in organ weight, organ indices, and the coefficient of the visceral brain between the SD rats in the different dosage groups and the SD rats in the vehicle control group (P > 0.05). Histopathological observations showed that there was no correlation between the pathological lesions of the organs observed in this study and the dose of Fe2O3 NPs (P > 0.05). The no-observed-adverse-effect level (NOAEL) dose of Fe2O3 NPs was initially determined to be 500 mg/kg administered to SD rats through oral gavage for 94 d, consecutively, followed by recovery after Fe2O3 NPs withdrawal for 30 d.


Assuntos
Nanopartículas , Ratos , Animais , Ratos Sprague-Dawley , Administração Oral , Relação Dose-Resposta a Droga , Nanopartículas/toxicidade , Tamanho do Órgão , Testes de Toxicidade Subcrônica
20.
Soc Sci Med ; 320: 115755, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36739708

RESUMO

BACKGROUND: Research suggests that structural racism and homophobia are associated with mental well-being. However, structural discrimination measures which are relevant to lived experiences and that evade self-report biases are needed. Social media and global-positioning systems (GPS) offer opportunity to measure place-based negative racial sentiment linked to relevant locations via precise geo-coding of activity spaces. This is vital for young sexual minority men (YSMM) of color who may experience both racial and sexual minority discrimination and subsequently poorer mental well-being. METHODS: P18 Neighborhood Study (n = 147) data were used. Measures of place-based negative racial and sexual-orientation sentiment were created using geo-located social media as a proxy for racial climate via socially-meaningfully-defined places. Exposure to place-based negative sentiment was computed as an average of discrimination by places frequented using activity space measures per person. Outcomes were number of days of reported poor mental health in last 30 days. Zero-inflated Poisson regression analyses were used to assess influence of and type of relationship between place-based negative racial or sexual-orientation sentiment exposure and mental well-being, including the moderating effect of race/ethnicity. RESULTS: We found evidence for a non-linear relationship between place-based negative racial sentiment and mental well-being among our racially and ethnically diverse sample of YSMM (p < .05), and significant differences in the relationship for different race/ethnicity groups (p < .05). The most pronounced differences were detected between Black and White non-Hispanic vs. Hispanic sexual minority men. At two standard deviations above the overall mean of negative racial sentiment exposure based on activity spaces, Black and White YSMM reported significantly more poor mental health days in comparison to Hispanic YSMM. CONCLUSIONS: Effects of discrimination can vary by race/ethnicity and discrimination type. Experiencing place-based negative racial sentiment may have implications for mental well-being among YSMM regardless of race/ethnicity, which should be explored in future research including with larger samples sizes.


Assuntos
Racismo , Minorias Sexuais e de Gênero , Mídias Sociais , Masculino , Humanos , Saúde Mental , Homofobia , Racismo Sistêmico , Racismo/psicologia , Atitude
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