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BACKGROUND: This study aimed to analyze the trends and burden of occupational exposure to asbestos in the United States (U.S.) from 1990 to 2019, focusing on mortality rates, geographic distribution, age and sex patterns, and causes of death. METHODS: Data on the number of deaths attributable to occupational exposure to asbestos were collected from 1990 to 2019 in the U.S. Joinpoint analysis was conducted to assess trends over time, and regression models were applied to calculate annual percentage changes (APC) and annual average percentage changes (AAPC). Geographic distribution was examined using mapping techniques. Age and sex patterns were analyzed, and causes of death were identified based on available data. RESULTS: From 1990 to 2019, the overall number of deaths due to occupational exposure to asbestos in the U.S. increased by 20.2%. However, age-standardized mortality rates (ASMR) and age-standardized disability-adjusted life years (DALYs) rates (ASDR) exhibited a decline over the same period. Geographic analysis revealed differences in the number of deaths across states in 2019, with California reporting the highest number of fatalities. Age-specific mortality and DALYs showed an increase with age, peaking in older age groups. Tracheal, bronchus, and lung cancer were the leading causes of death attributed to asbestos exposure, with increasing trends observed over the past five years. CONCLUSION: The study highlights significant trends and burden in occupational exposure to asbestos in the U.S., including overall increases in mortality rates, declining ASMR and ASDR, geographic disparities, age and sex patterns, and shifts in causes of death. These findings underscore the importance of continued monitoring and preventive measures to mitigate the burden of asbestos-related diseases.
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Amianto , Causas de Morte , Exposição Ocupacional , Humanos , Estados Unidos/epidemiologia , Masculino , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/estatística & dados numéricos , Feminino , Causas de Morte/tendências , Pessoa de Meia-Idade , Idoso , Adulto , Anos de Vida Ajustados por Deficiência/tendênciasRESUMO
Supercritical water gasification technology provides a favorable technology to achieve pollution elimination and resource utilization of phenolic wastewater. In this study, the reaction mechanism of phenolic wastewater supercritical water gasification was investigated using a combination of experimental and computational methods. Five reaction channels were identified to elucidate the underlying pathway of phenol decomposition. Importantly, the rate-determining step was found to be the dearomatization reaction. By integrating computational and experimental analyses, it was found that phenol decomposition via the path with the lowest energy barrier generates cyclopentadiene, featuring a dearomatization barrier of 70.97 kcal/mol. Additionally, supercritical water plays a catalytic role in the dearomatization process by facilitating proton transfer. Based on the obtained reaction pathway, alkali salts (Na2CO3 and K2CO3) are employed as a catalyst to diminish the energy barrier of the rate-determining step to 40.00 kcal/mol and 37.14 kcal/mol. Alkali salts catalysis significantly improved carbon conversion and pollutant removal from phenolic wastewater, increasing CGE from 58.44% to 93.55% and COD removal efficiency from 94.11% to 99.79%. Overall, this study provides a comprehensive understanding of the decomposition mechanism of phenolic wastewater in supercritical water.
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Águas Residuárias , Águas Residuárias/química , Catálise , Fenóis/química , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Água/químicaRESUMO
BACKGROUND: This research aimed to investigate the roles of fanconi anemia complementation group D2 (FANCD2) on the regulation of ferroptosis in osteosarcoma progression. METHODS: The function of FANCD2 on cell viability, invasion, migration, and tumor growth were explored. FANCD2 and pathway-related genes were determined by western blot. Ferroptosis-associated markers were determined, including lipid peroxidation, labile iron pool (LIP), ferrous iron (Fe2+), and ferroptosis-related genes. RESULTS: FANCD2 expression was increased in osteosarcoma cells. FANCD2 knockdown reduced cell viability, invasion, and migration of osteosarcoma cells. FANCD2 knockdown regulated ferroptosis-related gene expression, and distinctly increased the levels of LIP, Fe2+, and lipid peroxidation, and these effects were reversed by a ferroptosis inhibitor Fer-1. In addition, JAK2 and STAT3 expression were reduced by silencing of FANCD2, and STAT3 activator (colivelin) distinctly reversed tumor suppressor effects of FANCD2 silencing on osteosarcoma development. CONCLUSION: These findings suggested that FANCD2 silencing could suppress osteosarcoma cell viability, migration, invasion, and tumor growth, and induced ferroptosis by regulating the JAK2/STAT3 axis. These findings may provide novel therapeutic ideas for clinical treatment of osteosarcoma.
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Neoplasias Ósseas , Proteína do Grupo de Complementação D2 da Anemia de Fanconi , Ferroptose , Osteossarcoma , Humanos , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo , Ferro/farmacologia , Janus Quinase 2/metabolismo , Osteossarcoma/metabolismo , Fator de Transcrição STAT3/metabolismoRESUMO
Supercritical water gasification (SCWG) is an advanced and highly efficient method for treating oily sludge. However, it is crucial to consider the transformation characteristics of heavy metals (HMs) during the SCWG process to prevent potential secondary pollution. This work studied the transformation and distribution characteristics of Cu, Cr and Zn after SCWG of oily sludge in a batch reactor at temperatures ranging from 550 to 700 °C. Additionally, thermodynamic equilibrium analysis was conducted to assess the distribution of HMs based on the minimization of Gibbs free energy. Experimental results indicated that higher temperatures led to the conversion of HMs into more stable forms, effectively immobilizing them within solid products. Furthermore, the addition of Na2CO3 enhanced this process and contributed to a reduction in HMs pollution in the effluent. Thermodynamic equilibrium results were consistent with our experimental data, indicating that the molar fraction of stable HMs forms followed the order: Cr > Cu > Zn. Besides, it is worth noting that Na2CO3 had a limited impact on the distribution of Cu and Cr. However, it played a significant role in inhibiting the formation of silicate Zn at lower temperatures, promoting the decomposition of ZnO*Al2O3 into unstable Zn. This may explain the higher presence of unstable Zn when Na2CO3 was introduced. In summary, this study offers valuable insights into the transformation characteristics of heavy metals and strategies for pollution control during SCWG of oily sludge.
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Metais Pesados , Esgotos , Água , Termodinâmica , TemperaturaRESUMO
Realizing the harmless resource utilization of oily sludge is urgent for petroleum industry and of great significance for environmental management. The treatment of oily sludge was investigated using supercritical water gasification (SCWG) with a continuous fluidized bed reactor. The effect of operating parameters on gasification efficiency and gas yield without catalyst was tested, and then the influences of catalyst type (K2CO3 and Na2CO3) and concentrations (1-8 wt%) were systematically studied. The results indicated that a medium mass flow ratio and low feedstock concentration were beneficial for gas production. Alkali catalyst improved carbon gasification efficiency (CE) prominently, and Na2CO3 showed better performance due to its better stability. A maximum CE of 95.87% was achieved when 5 wt% Na2CO3 was added at 650 °C, 23 MPa with 5 wt% oily sludge concentration. Besides, according to XRD patterns of solid residues, Na2CO3 was more stable than K2CO3 during SCWG. SEM-EDX results also revealed that more K was migrated into solid residues than Na. The analysis of pore structure demonstrated that alkali catalyst promoted the evolution of pore structure, resulting in higher specific surface areas and total pore volumes. Na2CO3 has a more substantial destructive effect on solid matrix, causing the matrix structure to collapse and inhibiting pore structure development. The FTIR spectra of solid products exhibited a lower content of carbohydrates and aromatic structures than the initial oily sludge. NH4-N results demonstrated that SCWG was a potential green treatment process for oily sludge. This work can not only give an insight into the reaction mechanism of alkali catalytic gasification of oily sludge, but also help to guide the optimal design of reactor and the regulation of operating parameters.
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Álcalis , Esgotos , Água/química , Carbono , Catálise , ÓleosRESUMO
BACKGROUND: Histological grade has been demonstrated to be an important factor of breast cancer outcome and is associated with cell differentiation and is currently being evaluated via H&E-stained sections. Molecular biomarkers are essential to improve the accuracy of histological grading. ATBF1, a large transcription factor, has been considered a tumor suppressor gene with frequent mutations or deletions in multiple cancers. In breast cancer, ATBF1 was reported to function in cell differentiation and mammary development. However, its role in the clinic has rarely been reported. METHODS: Breast cancer tissues (BCTs) and adjacent noncancerous tissues (ANCTs) were collected to analyze the expression of ATBF1 at the mRNA and protein levels. Three anti-ATBF1 antibodies recognizing independent peptides of ATBF1 (N-terminal end, middle region and C-terminal end) were applied for IHC staining. Small interfering RNA (siRNA) was used to silence ATBF1 expression and to investigate the roles of ATBF1 in MCF7 cells. Microarrays were introduced to analyze the differentially expressed genes, enriched GO terms and KEGG terms regulated by ATBF1 and its potential downstream genes, which were further confirmed in vitro and in clinical samples. RESULTS: The expression of ATBF1 was reduced in BCTs at both the mRNA and protein levels compared with that in ANCTs. ATBF1 protein was predominantly localized in the nucleus of ANCTs but in the cytoplasm of BCTs. Both the mRNA and protein levels of ATBF1 were significantly correlated with histological grade. Consistently, knockdown of ATBF1 increased stemness marker expression and reduced differentiation markers in vitro. Further analysis identified WNT5A as an essential downstream gene of ATBF1 in breast cancer cells. Treatment of WNT5A disrupted cell proliferation induced by ATBF1 silencing. In BCTs, a significant correlation was observed between the expression of WNT5A and ATBF1. CONCLUSION: The results indicated that ATBF1 expression might be a useful diagnostic marker associated with histological grade and breast cancer malignancy. WNT5A and its signaling pathway are novel mechanisms by which ATBF1 contributes to breast cancer tumorigenesis.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , RNA Mensageiro , Proteína Wnt-5aRESUMO
A total of 15 novel-substituted 3-(benzylsulfanyl)-1H-1,2,4-triazol-5-ylamine and 10 novel-substituted 3-benzylmercapto-1,2,4-triazol derivatives were synthesized based on the natural product phenazine-1-carboxylic acid (PCA). Their structures were confirmed by 1H-NMR, 13C-NMR, HRMS, and X-ray. Most substituted 3-benzylmercapto-1,2,4-triazol derivatives displayed very strong fungicidal activity against one or multiple plant pathogens in vitro and in vivo. Compounds 8b, 8h, and 8i showed a broad spectrum of fungicidal activity. Further field experiments indicated that compounds 8b, 8c, and 8h displayed better efficacy against rice blast (Pyricularia oryzae) than PCA. These data demonstrate that compounds 8b, 8c, and 8h are promising fungicidal candidates, deserving further studies.[Formula: see text].
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Fungicidas Industriais , Fenazinas , Ascomicetos , Fungicidas Industriais/farmacologia , Estrutura Molecular , Fenazinas/farmacologia , Relação Estrutura-Atividade , Triazóis/farmacologiaRESUMO
Purpose: The function of long noncoding RNAs (lncRNA) in breast cancer metastasis remains largely unknown. In this work, the role of HOXC-AS3 in breast cancer progression was investigated.Methods: By using Cancer Genome Atlas (TCGA) Database, we investigated the expression of HOXC-AS3 in breast cancer and explored the association between HOXC-AS3 expression and prognosis. Then, we studied the biological function of HOXC-AS3 in cell migration and invasion both in vitro and in vivo. Furthermore, the target miRNA of HOXC-AS3, and the target mRNA of miR-3922-5p were proved.Results: HOXC-AS3 is aberrantly overexpressed in breast cancers especially the HER2+ type. Moreover, high expression of HOXC-AS3 has a relationship with poor clinical outcomes of breast cancer. In addition, HOXC-AS3 regulates cell Invasion and migration both in vitro and in vivo. Our results demonstrated that miR-3922-5p was a direct target of HOXC-AS3, and PPP1R1A was a target of miR-3922-5p in breast cancer.Conclusions: The novel lncRNA HOXC-AS3 acts as a miR-3922-5p sponge to upregulate PPP1R1A protein expression, and thus results in promoting breast cancer metastasis. HOXC-AS3 could be a novel therapeutic target for breast cancer therapeutics.
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Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteína Fosfatase 1/genética , RNA Longo não Codificante/metabolismo , Animais , Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Conjuntos de Dados como Assunto , Feminino , Humanos , Camundongos , MicroRNAs/metabolismo , Prognóstico , Análise de Sobrevida , Fatores de Tempo , Regulação para Cima , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: This study assessed outcomes after treatment of patients with capitellum fracture diagnosed >4 weeks after the trauma (delayed) who presented with stiff elbow. METHODS: We reviewed 7 patients with stiff elbows after delayed diagnosis of capitellum fractures between February 2007 and February 2012. They were treated with arthrolysis by twin incisions, late open reduction and internal fixation, and a hinged external fixator. According to the Bryan-Morrey-McKee classification, 3 patients had type I capitellum fractures and 4 patients had type IV. RESULTS: Mean follow-up was 28 months (range, 24-38 months). The mean delay from the initial trauma was 3.7 months. The flexion arc improved from a preoperative mean of 24° to a postoperative mean of 122°. The Mayo Elbow Performance Score increased from a mean of 56 points to 93 points. Anatomic fracture union occurred in all cases, and there was no secondary displacement. CONCLUSIONS: Arthrolysis, late internal fixation, and use of a hinged external fixator can solve problems associated with stiff elbow after delayed diagnosis of capitellum fracture. Combined use of these techniques may be a safe and effective treatment option.
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Anquilose/cirurgia , Fixadores Externos , Fixação Interna de Fraturas , Fraturas Mal-Unidas/cirurgia , Fraturas não Consolidadas/cirurgia , Fraturas do Úmero/cirurgia , Adolescente , Adulto , Anquilose/etiologia , Diagnóstico Tardio , Articulação do Cotovelo/cirurgia , Feminino , Fraturas Mal-Unidas/complicações , Fraturas não Consolidadas/complicações , Humanos , Fraturas do Úmero/complicações , Fraturas do Úmero/diagnóstico , Fraturas Intra-Articulares/complicações , Fraturas Intra-Articulares/diagnóstico , Fraturas Intra-Articulares/cirurgia , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Tempo para o Tratamento , Resultado do Tratamento , Adulto Jovem , Lesões no CotoveloRESUMO
INTRODUCTION: The treatment of terrible triad injury with a poor outcome after intervention has not been successful thus far. The purpose of this study was to evaluate the efficacy of arthrolysis and reconstruction in the treatment of terrible triad injury with a poor outcome after surgical as well as conservative intervention. MATERIALS AND METHODS: Twelve patients (12 elbows) with the diagnosis of terrible triad injury were respectively reviewed. All the 12 patients had elbow dysfunction after conservative and surgical treatment of the terrible triad injury. Preoperatively, the flexion arc and forearm rotation were 36.7° ± 28.5° and 51.3° ± 43.4°, respectively, and the Mayo Elbow Performance Score was 56.3 points. The mean interval between the primary injury and our surgical treatment was 6.6 months. Our surgical intervention included elbow arthrolysis, ulnar nerve transposition, radial head replacement, coronoid process and ligament repair, and hinged external fixation. Patients were encouraged to participate in rehabilitation training 24 h after surgery. RESULTS: The mean follow-up duration was 20.1 months; the flexion arc and forearm rotation were 122° ± 18° and 140° ± 20°, respectively, and the mean Mayo Elbow Performance Score was 94.6 points (9 excellent, 3 good). Concentric stability was restored in all elbows. Complications included superficial pin tract infection (1), heterotopic ossification (3), and ulnar nerve palsy (1); the ulnar nerve symptoms had improved at the last follow-up. CONCLUSIONS: The combination of open arthrolysis and reconstruction performed at a mean interval of 6-month posttrauma can restore functional mobility in cases of terrible triad injury with a poor outcome after surgical as well as conservative intervention. Thus, it may be an effective alternative for the treatment of the poor outcome terrible triad injury. We recommend early functional rehabilitation with adherence to the guidelines for hinged external fixation.
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Artroplastia de Substituição do Cotovelo/métodos , Lesões no Cotovelo , Articulação do Cotovelo/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Adulto , Artroplastia de Substituição do Cotovelo/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Amplitude de Movimento Articular , Procedimentos de Cirurgia Plástica/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
The thermal debinding-sintering process plays an essential role in the context of material extrusion-based additive manufacturing (AM) for producing parts using metal injection molding (MIM). During thermal debinding, metal parts often experience material distortion and porosity, which negatively impacts their mechanical properties. Slowing down the debinding speed is a common approach to mitigate material distortion and porosity. However, this leads to a significant increase in the debinding time. In this study, we carried out debinding-sintering experiments to optimize the distortion and porosity in metal parts. These metal parts were manufactured utilizing bronze/polylactide (PLA) blend filaments and placed in crucibles of different sizes (small, medium, and large), with different heating rates and holding times. The results revealed that the small crucible yielded higher porosity levels in the metal parts, which could be reduced from 23% to 12% by extending both the heating and holding times. In contrast, the medium crucible managed to reduce porosity to approximately 15% without requiring an extension of the processing time. The large crucible, on the other hand, couldn't achieve further porosity reduction due to challenges in reaching the desired temperature. To gain a deeper insight into temperature distribution during the debinding process, we performed numerical simulations using the computational fluid dynamics (CFD) technique and obtained temperature profiles within the kiln using the three crucibles. Ultimately, we carried out standard mechanical tests on the resulting metal parts and evaluated the thermal debinding procedure under various conditions. The approach we employed, combining experiments and numerical simulations, demonstrated significant promise for enhancing the quality of metal parts in the thermal debinding-sintering process.
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TRIM58 is a member of the TRIM protein family, which possess with E3 ubiquitin ligase activities. Studies have revealed that low expression of TRIM58 plays key roles, has been implicated in the tumor progression of tumor formation due to its reduced expression. However, its role in regulating the stemness of breast cancer stem cells (CSCs) remains unexplored. Here, we found that TRIM58 was underexpressed in TNBC tissues and cells compared to adjacent mucosa tissue, and its downregulation was significantly associated with shorter survival. Overexpression of TRIM58 reduced the proportion of CD44 + /CD24- cells, upregulated differentiation genes, and inhibited stemness-related gene expression in TNBC CSCs. In vitro and in vivo experiments revealed that TRIM58 overexpression in CSCs suppressed tumor sphere formation and tumorigenic capacity. Co-IP results indicated direct interaction between TRIM58 and MYH9, with TRIM58 inducing MYH9 degradation via ubiquitination in differentiated cells. Label-free quantitative proteomics identified GRK3 and Hippo-YAP as downstream targets and signaling pathways of MYH9. TIMER database analysis, immunohistochemistry, western blotting, DNA-protein pulldown experiments, and dual luciferase reporter assays demonstrated that MYH9 regulated GRK3 transcriptional activation in CSCs. In conclusion, elevated TRIM58 expression in CSCs downregulates MYH9 protein levels by promoting ubiquitin-mediated degradation, thereby inhibiting downstream GRK3 transcription, inactivating the YAP stemness pathway, and ultimately promoting CSC differentiation.
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Regulação para Baixo , Cadeias Pesadas de Miosina , Células-Tronco Neoplásicas , Neoplasias de Mama Triplo Negativas , Humanos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Feminino , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Camundongos , Animais , Cadeias Pesadas de Miosina/metabolismo , Cadeias Pesadas de Miosina/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas com Motivo Tripartido/metabolismo , Proteínas com Motivo Tripartido/genética , Transdução de Sinais , Linhagem Celular Tumoral , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Regulação Neoplásica da Expressão Gênica , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Proteínas de Sinalização YAP/metabolismo , Proteínas de Sinalização YAP/genéticaRESUMO
Circular RNA Ribonuclease P RNA Component H1 (circ_RPPH1) and microRNA (miRNA) miR-1296-5p play a crucial role in breast cancer (BC), but the molecular mechanism is vague. Evidence showed that miR-1296-5p can activate tripartite motif-containing 14 (TRIM14). Clinical indications of eighty BC patients were collected and the circ_RPPH1 expression was detected using real-time quantitative PCR. MCF-7 and MDA-MB-231 cells were transfected with overexpression or knockdown of circ_RPPH1, miR-1296-5p, or TRIM14. Cell counting kit-8, cell cloning formation, wound healing, Transwell, and flow cytometry assays were performed to investigate the malignant phenotype of BC. The dual-luciferase reporter gene analyses were applied to reveal the interaction between these target genes. Subcutaneous tumorigenic model mice were established with circ_RPPH1 overexpression MDA-MB-231 cells in vivo; the tumor weight and volume, levels of miR-1296-5 and TRIM14 mRNA were measured. Western blot and immunohistochemistry were used to detect TRIM14 in cells and mice. Circ_RPPH1 levels were notably higher in BC patients and have been found to promote cell proliferation, invasion, and migration of BC cells. Circ_RPPH1 altered cell cycle and hindered apoptosis. Circ_RPPH1 knockdown or miR-1296-5p overexpression inhibited the malignant phenotype of BC. Furthermore, miR-1296-5p knockdown reversed circ_RPPH1's promotion effects on BC. Interestingly, TRIM14 overexpression counteracts the inhibitory effects of miR-1296-5p overexpression and circ_RPPH1 silencing on BC. Moreover, in BC tumor-bearing mice, circ_RPPH1 overexpression led to increased TRIM14 expression and facilitated tumor growth. Circ_RPPH1 enhanced BC progression through miR-1296-5p/TRIM14 axis, indicating its potential as a biomarker and therapeutic target in BC.
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Neoplasias da Mama , Proliferação de Células , Progressão da Doença , MicroRNAs , RNA Circular , Proteínas com Motivo Tripartido , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Proteínas com Motivo Tripartido/genética , Animais , Camundongos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Apoptose , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética , Linhagem Celular Tumoral , Camundongos NusRESUMO
Introduction: The close association between cuproptosis and tumor immunity in triple-negative breast cancer (TNBC) allows its monitoring for predicting the prognosis of patients with TNBC. Nevertheless, the biological function and prognostic value of cuproptosis-related miRNAs and their target genes have not been reported. Purpose: To construct the miRNA and mRNA-based risk models associated with cuproptosis for patients with TNBC. Methods: Comparison of expression levels for genes associated with cuproptosis was executed between patients in the normal individuals and the TCGA-TNBC cohort. Conducting differential analysis resulted in the identification of differentially expressed miRNA (DE-miRNAs) and differentially expressed genes (DEGs) between the TNBC and Control samples. Screening for prognostic miRNAs and biomarkers involved employing univariate Cox analysis and least absolute shrinkage and selection operator regression analyses. These methods were utilized to construct risk models aimed at predicting the survival of patients with TNBC. Based on the median value of risk scores, patients were then stratified into low- and high-risk groups. Functional enrichment analysis was employed to explore the potential function and pathways of prognostic genes. Additionally, independent prognostic analysis was performed through univariate and multivariate Cox regression. Immune infiltration analysis was performed to examine disparities in the infiltration of immune cells between the two risk groups. Finally, the prognostic gene expression was mined in key cell types of TNBC. Results: We obtained 5213 DEGs and 204 DE-miRNAs related to cuproptosis between TNBC and Control samples. Five prognostic miRNAs (miR-203a-3p, miR-1277-3p, miR-135b-5p, miR-200c-3p, and miR-592) and three biomarkers (DENND5B, IGF1R, and MEF2C) were closely associated with TNBC. Significant differences in the functions of prognostic genes between the two risk groups were observed, encompassing adipogenesis, inflammatory response, and hormone metabolic process. The prognostic gene regulatory network revealed that miR200C-3p regulated ZFPM2 and CFL2, and miR-1277-3p regulated BMP2 and RORA. A nomogram was created based on riskScore, cancer status, and pathologic stage to predict 1/3/5-year survival of patients with TNBC. Immune infiltration analysis indicated that the immune microenvironment may be associated with the progression of TNBC. Interestingly, prognostic genes exhibited higher expression levels in T cells, fibroblasts, endothelial cells, and monocytes compared to other cells. Conclusions: Five prognostic miRNA (miR-203a-3p, miR-1277-3p, miR-135b-5p, miR-200c-3p, and miR-592) and three biomarkers (DENND5B, IGF1R, and MEF2C) were significantly associated with TNBC, it provides new therapeutic targets for the treatment and prognosis of TNBC.
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Understanding the paleoenvironment and phytogeographical history of the Tibetan Plateau, China relies on discovering new plant fossils. The Qaidam Basin has long been regarded as an ideal 'field laboratory' to investigate the paleoclimate and paleobiological evolution of the northern Tibetan Plateau. However, fossil angiosperms from the Qaidam Basin are rare, and our knowledge of its paleovegetation is poor. Here, we report fossil leaves and fruits of Betulaceae found from the Oligocene Shangganchaigou Formation of northwestern Qaidam Basin (Huatugou area). Comparative morphological analysis led us to assign the fruits to the Betula subgenus Betula and the leaves to Carpinus grandis. These findings, together with other reported fossil plants from the same locality, reveal a close floristic linkage between the Qaidam Basin and Europe during the Oligocene. The northern pathway of this floristic exchange may have crossed through the Qaidam Basin during the late Paleogene. This floristic linkage may have been facilitated by the continuous narrowing of the Turgai Strait and stronger westerlies, which transported moisture and provided favorable climatic conditions. Indeed, fossil plants collected from the Qaidam Basin suggest that during the Oligocene this region had warm and humid deciduous broad-leaf forest, which differs from the region's modern vegetation and indicates that the Qaidam Basin may have been a suitable region for these plants to flourish and spread during the Oligocene.
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Doxorubicin (Dox) poses a considerable threat to patients owing to its cardiotoxicity, thus limiting its clinical utility. Optimal cardioprotective intervention strategies are needed to suppress tumor growth but also minimize cardiac side effects. Here, we showed that tragus vagus nerve stimulation (tVNS) improved the imbalanced autonomic tone, ameliorated impaired cardiac function and fibrosis, attenuated myocyte apoptosis, and mitochondrial dysfunction compared to those in the Dox group. The beneficial effects were attenuated by methyllycaconitine citrate (MLA). The transcript profile revealed that there were 312 differentially expressed genes and the protection of tVNS and retardation of MLA were related to inflammatory response and NADPH oxidase activity. In addition, tVNS synergizing with Dox inhibited tumor growth and lung metastasis and promoted apoptosis of tumor cells in an anti-tumor immunity manner. These results indicated that non-invasive neuromodulation can play a dual role in preventing Dox-induced cardiotoxicity and suppressing tumor growth through inflammation and oxidative stress.
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BACKGROUND: Limited forearm rotation is a frequent combined disorder in elbow stiffness. If the radial head cannot be saved during open arthrolysis, prosthetic replacement might be considered because it enhances stability and allows early motion. METHODS: In this study we retrospectively analyzed the outcome of 8 patients (7 men, 1 woman) who underwent open arthrolysis and simultaneous prosthetic replacement after resection of the radial head to restore elbow range of motion and forearm rotation. Patients were a mean age of 31.7 years (range, 22-40 years). RESULTS: Postoperatively, the mean (range) active range of motion improved from 29.4° (0°-70°) to 113.1° (80°-135°), mean (range) supination increased from 38.8° (0°-80°) to 77.5° (50°-90°), and mean (range) pronation improved from 18.8° (0°-80°) to 68.8° (50°-80°). The Mayo Elbow Performance Score improved from a mean (range) of 57.5 (50-70) to 92.5 (85-100) points. No elbow valgus instability was detected over a mean duration of 26 months of follow-up. The implant was considered stable in all patients. CONCLUSIONS: Open arthrolysis and prosthetic replacement of the radial head are effective in treating elbow stiffness with associated rotation limitation after resection of the radial head.
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Articulação do Cotovelo/cirurgia , Fraturas Ósseas/cirurgia , Rádio (Anatomia)/cirurgia , Adulto , Artroplastia de Substituição , Feminino , Antebraço , Humanos , Masculino , Rádio (Anatomia)/lesões , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Estudos Retrospectivos , Rotação , Adulto Jovem , Lesões no CotoveloRESUMO
Tendon adhesions are one of the most concerning complications after surgical repair of flexor tendon injury. Extracellular signal-regulated kinase (ERK) 2 plays crucial roles in fibroblast proliferation and collagen expression which contributes to the formation of tendon adhesions after flexor tendon surgery. Using a chicken model, we have examined the effects of a small interfering RNA (siRNA) targeting ERK2 delivered by a lentiviral system on tendon adhesion formation with an adhesion scoring system, histological assessment, and biomechanical evaluation. It was found that ERK2 siRNA effectively suppressed the increase of fibroblasts and the formation of tendon adhesions (p < 0.05 compared with the control group). Moreover, no statistically significant reduction in breaking force was detected between the ERK2 siRNA group and the control group. These results show that the lentiviral-mediated siRNA system is effective in preventing tendon adhesion formation but not to tendon healing, and may be used for tendon repair after confirmation and improvement by future detailed studies.
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Supercritical water gasification (SCWG) technology can convert oily sludge into hydrogen-rich gas. To achieve high gasification efficiency of oily sludge with a high oil concentration under mild conditions, a two-step method involving a desorption process and a catalytic gasification process using Raney-Ni catalyst was investigated. High oil removal efficiency (99.57%) and carbon gasification efficiency (93.87%) were achieved. The lowest wastewater total organic carbon, oil content, and carbon content in the solid residues were 4.88 ppm, 0.08% and 0.88%, respectively, using a gasification temperature of 600 °C, treatment concentration of 1.11 wt%, gasification time of 70.7 s, and the optimal desorption temperature of 390 °C. The main organic carbon component in the solid residues was cellulose, which is environmentally safe. As the treatment concentration increased, the two-step method outperformed the single-step method. The mechanism for the two-step SCWG of oily sludge was revealed. In the first step, supercritical water is used in the desorption unit to achieve a high oil removal efficiency with few liquid products generated. In the second step, the Raney-Ni catalyst promotes efficient gasification of high-concentration oil at a low temperature. This research provides valuable insights into the effective SCWG of oily sludge at a low temperature.
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Osteoarthritis (OA) is the most common disabling joint disease with no effective disease modifying drugs. Extracellular vesicles released by several types of mesenchymal stem cells could promote cartilage repair and ameliorate OA pathology in animal models, representing a novel therapeutic strategy. In this study, we demonstrated that extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUC-EVs) could maintain chondrocyte homeostasis and alleviate OA, and further revealed a novel molecular mechanism of this therapeutic effect. miR-223, which could directly bind with the 3'UTR of NLRP3 mRNA, was found to be a key miRNA for hUC-EVs to exert beneficial effects on inflammation inhibiting and cartilage protecting. For enhancing the effect on mitigating osteoarthritis, exogenous miR-223 was loaded into hUC-EVs by electroporation, and a collagen II-targeting peptide (WYRGRL) was modified onto the surface of hUC-EVs by genetic engineering to achieve a more targeted and efficient RNA delivery to the cartilage. The dual-engineered EVs showed a maximal effect on inhibiting the NLRP3 inflammasome activation and chondrocyte pyroptosis, and offered excellent results for the treatment of OA. This study provides a novel theoretical basis and a promising therapeutic strategy for the application of engineered extracellular vesicles in OA treatment.