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1.
Health Qual Life Outcomes ; 22(1): 59, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075537

RESUMO

OBJECTIVE: To evaluate and compare the measurement properties and consistency between the Chinese versions of EQ-5D-3L and EQ-5D-Y-3L among Chinese adolescent populations aged 15-17 years. METHODS: Chinese adolescents aged 15-17 studying in high school were recruited through online survey. Social-demographic characteristics and self-reported EQ-5D-3L and EQ-5D-Y-3L responses were collected in the survey. The consistency of responses between the two measures was assessed using redistribution property, and the consistency of utility values was assessed by intraclass correlation coefficients (ICC). Convergent validity and known-group validity were examined using Spearman's rank correlation, F-test and effect sizes, respectively. Sensitivity was compared using relative efficiency (RE). RESULTS: 762 respondents (48.8% male; age 15-17 years;) were recruited. The EQ-5D-3L showed a more severe ceiling effect than EQ-5D-Y-3L (78.2% vs. 66.0%). Respondents reported higher proportions of having problems in four dimensions using the EQ-5D-Y-3L than using the EQ-5D-3L. The consistency of corresponding dimensions between the two measures was relatively good, while non-negligible proportions of inconsistency were observed in "pain/discomfort" (11.4%) and "anxiety/depression" (15.7%) dimensions. The ICC of the utility values between the EQ-5D-3L and EQ-5D-Y-3L was 0.852 (p < 0.001). The Spearman's rank correlation (range: 0.385-0.620) indicated an acceptable convergent validity between the correlative dimensions of the EQ-5D-3L and EQ-5D-Y-3L. The EQ-5D-Y-3L had a higher efficiency than the EQ-5D-3L at detecting differences across EQ VAS subgroups (ES = 1.793 for EQ-5D-3L, ES = 1.920 for EQ-5D-Y-3L). Mixed results were observed in sensitivity. CONCLUSIONS: Both the EQ-5D-3L and EQ-5D-Y-3L are demonstrated to be valid and generally consistent for measuring HRQoL among adolescents aged 15-17 years in China. Respondents reported higher proportions of having problems using the EQ-5D-Y-3L than using the EQ-5D-3L. More research is warranted to compare the discriminant validity and test-retest reliability between the two measures.


Assuntos
Psicometria , Qualidade de Vida , Humanos , Adolescente , Masculino , China , Feminino , Inquéritos e Questionários/normas , Reprodutibilidade dos Testes , Psicometria/normas , Nível de Saúde
2.
Bioresour Technol ; 409: 131240, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39122129

RESUMO

To promote the sustainability of hydrothermal liquefaction (HTL) for biofuel production, fungal fermentation was investigated to treat HTL aqueous phase (HTLAP) from corn stover. The most promising fungus, Aspergillus niger demonstrated superior tolerance to HTLAP and capability to produce oxalic acid as a value-added product. The fungal-bacterial co-culture of A. niger and Rhodococcus jostii was beneficial at low COD (chemical oxygen demand) loading of 3800 mg/L in HTLAP, achieving 69% COD removal while producing 0.5 g/L oxalic acid and 11% lipid content in microbial biomass. However, higher COD loading of 4500, 6040, and 7800 mg/L significantly inhibited R. jostii, but promoted A. niger growth with increased oxalic acid production while COD removal remained similar (58-65%). Additionally, most total organic carbon (TOC) in HTLAP was transformed into oxalic acid, representing 46-56% of the consumed TOC. These findings highlighted the potential of fungi for bio-upcycling of HTLAP into value-added products.

3.
Water Res ; 257: 121654, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38701552

RESUMO

Volatile fatty acids (VFAs) derived from arrested anaerobic digestion (AD) can be recovered as a valuable commodity for value-added synthesis. However, separating VFAs from digestate with complex constituents and a high-water content is an energy-prohibitive process. This study developed an innovative technology to overcome this barrier by integrating deep eutectic solvents (DESs) with an omniphobic membrane into a membrane contactor for efficient extraction of anhydrous VFAs with low energy consumption. A kinetic model was developed to elucidate the mechanistic differences between this novel omniphobic membrane-enabled DES extraction and the previous hydrophobic membrane-enabled NaOH extraction. Experimental results and mechanistic modeling suggested that VFA extraction by the DES is a reversible adsorption process facilitating subsequent VFA separation via anhydrous distillation. High vapor pressure of shorter-chain VFAs and low Nernst distribution coefficients of longer-chain VFAs contributed to DES-driven extraction, which could enable continuous and in-situ recovery and conversion of VFAs from AD streams.


Assuntos
Ácidos Graxos Voláteis , Interações Hidrofóbicas e Hidrofílicas , Membranas Artificiais , Solventes Eutéticos Profundos/química , Solventes/química , Cinética , Anaerobiose
4.
World J Gastroenterol ; 30(6): 565-578, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38463028

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with limited treatment options. Deubiquitinases (DUBs) have been confirmed to play a crucial role in the development of malignant tumors. JOSD2 is a DUB involved in controlling protein deubiquitination and influencing critical cellular processes in cancer. AIM: To investigate the impact of JOSD2 on the progression of ESCC. METHODS: Bioinformatic analyses were employed to explore the expression, prognosis, and enriched pathways associated with JOSD2 in ESCC. Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines (KYSE30 and KYSE150). Functional assays, including cell proliferation, colony formation, drug sensitivity, migration, and invasion, were performed, revealing the impact of JOSD2 on ESCC cell lines. JOSD2's role in xenograft tumor growth and drug sensitivity in vivo was also assessed. The proteins that interacted with JOSD2 were identified using mass spectrometry. RESULTS: Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues, which was associated with poor prognosis. Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells. JOSD2 knockdown inhibited ESCC cell activity, including proliferation and colony-forming ability. Moreover, JOSD2 knockdown decreased the drug resistance and migration of ESCC cells, while JOSD2 overexpression enhanced these phenotypes. In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC. Mechanistically, JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways. Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2, which identified the four primary proteins that bind to JOSD2, namely USP47, IGKV2D-29, HSP90AB1, and PRMT5. CONCLUSION: JOSD2 plays a crucial role in enhancing the proliferation, migration, and drug resistance of ESCC, suggesting that JOSD2 is a potential therapeutic target in ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Enzimas Desubiquitinantes/genética , Regulação Neoplásica da Expressão Gênica , Proteína-Arginina N-Metiltransferases
5.
Eur J Med Chem ; 271: 116395, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38626523

RESUMO

The transforming growth factor ß1 (TGFß1)/SMAD signaling pathway regulates many vital physiological processes. The development of potent inhibitors targeting activin receptor-like kinase 5 (ALK5) would provide potential treatment reagents for various diseases. A significant number of ALK5 inhibitors have been discovered, and they are currently undergoing clinical evaluation at various stages. However, the clinical demands were far from being met. In this study, we utilized an alternative conformation-similarity-based virtual screening (CSVS) combined with a fragment-based drug designing (FBDD) strategy to efficiently discover a potent and active hit with a novel chemical scaffold. After structural optimization in the principle of group replacement, compound 57 was identified as the most promising ALK5 inhibitor. Compound 57 demonstrated significant inhibitory effects against the TGF-ß1/SMAD signaling pathway. It could markedly attenuate the production of extracellular matrix (ECM) and deposition of collagen. Also, the lead compound showed adequate pharmacokinetic (PK) properties and good in vivo tolerance. Moreover, treatment with compound 57 in two different xerograph models showed significant inhibitory effects on the growth of pancreatic cancer cells. These results suggested that lead compound 57 refers as a promising ALK5 inhibitor both in vitro and in vivo, which merits further validation.


Assuntos
Desenho de Fármacos , Inibidores de Proteínas Quinases , Pirazóis , Pirimidinas , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptor do Fator de Crescimento Transformador beta Tipo I/antagonistas & inibidores , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Humanos , Pirazóis/farmacologia , Pirazóis/química , Pirazóis/síntese química , Pirimidinas/farmacologia , Pirimidinas/química , Pirimidinas/síntese química , Relação Estrutura-Atividade , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Animais , Estrutura Molecular , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Camundongos , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Receptores de Fatores de Crescimento Transformadores beta/antagonistas & inibidores , Receptores de Fatores de Crescimento Transformadores beta/metabolismo
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