RESUMEN
Polylactic acid (PLA) is a high-modulus, high-strength bio-based thermoplastic polyester with good biodegradability, which is currently a promising environmentally friendly material. However, its inherent brittleness has hindered its widespread use. In this study, we reported a simple and non-toxic strategy for toughening PLA, using biodegradable materials such as polyethylene glycol (PEG) and citric acid (CA) as precursors. Through reactive melt blending with PLA, PEG and CA form PEGCA copolyesters in situ during blending. At the same time, CA can react with PLA and PEG, forming a copolyester structure at the interface of the two phases, improving the interfacial compatibility between PEG and PEGCA with PLA. Fourier transform infrared spectroscopy confirms this. Experimental results show that when the content of PEG/CA reaches 15% (PLA/PEG/CA-15%) in the blends, the impact strength of the blend was 4.47 kJ m-2, and the maximum elongation at break was as high as 360.1%, which were about 2 and 44 times higher than those of pure PLA, respectively. Moreover, the tensile strength was still maintained at the level of 70%. This work can expand the application of PLA in food packaging and medical supplies.
RESUMEN
Portulacerebroside A (PCA), a cerebroside compound extracted from Portulaca oleracea L., has been shown to suppress hepatocellular carcinoma (HCC) cells. This study aims to investigate the effectiveness of trimethyl chitosan-cysteine (TMC-Cys) nanocarrier in delivering PCA for HCC management and to elucidate the molecular mechanisms behind PCA's function. TMC-Cys nanocarriers notably augmented PCA's function, diminishing the proliferation, migration, and invasiveness of HCC cells in vitro, reducing hepatocellular tumorigenesis in immunocompetent mice, and impeding metastasis of xenograft tumours in nude mice. Comprehensive bioinformatics analyses, incorporating Super-PRED systems alongside pathway enrichment analysis, pinpointed toll-like receptor 4 (TLR4) and epidermal growth factor receptor (EGFR) as two promising targets of PCA, enriched in immune checkpoint pathway. PCA/nanocarrier (PCA) reduced levels of TLR4 and EGFR and their downstream proteins, including programmed cell death ligand 1, thereby increasing populations and activity of T cells co-cultured with HCC cells in vitro or in primary HCC tumours in mice. However, these effects were counteracted by additional artificial activation of TLR4 and EGFR. In conclusion, this study provides novel evidence of PCA's function in immunomodulation in addition to its direct tumour suppressive effect. TMC-Cys nanocarriers significantly enhance PCA efficacy, indicating promising application as a drug delivery system.
Asunto(s)
Carcinoma Hepatocelular , Quitosano , Cisteína , Neoplasias Hepáticas , Ratones Desnudos , Nanopartículas , Receptor Toll-Like 4 , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Animales , Quitosano/química , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Humanos , Ratones , Receptor Toll-Like 4/metabolismo , Cisteína/química , Línea Celular Tumoral , Receptores ErbB , Proliferación Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Masculino , Movimiento Celular/efectos de los fármacos , Ratones Endogámicos BALB CRESUMEN
OBJECTIVE: The adverse impacts of meteorological factors on human health have attracted great attention. However, no studies have investigated the nonlinear effects of humidex on hip fractures (HF), particularly in middle-aged and older adults. This study aimed to quantify the impacts of humidex, a comprehensive index of temperature and relative humidity, on HF admissions. METHODS: Daily HF admissions, meteorological variables and air pollutants in the subtropical coastal city of Shantou, China, from 2015 to 2020 were collected. A generalized linear regression model combined with a distributed lag nonlinear model was applied to explore the exposure-lag-response relationship between humidex and HF admissions. Subgroup analyses were also conducted by gender, age and season. Attributable fractions (AF) and attributable numbers (AN) were used to represent the burden of disease. RESULTS: A total of 6200 HF admissions were identified during the study period. Taking the median humidex (31.9) as a reference, the single-day lag effects of low humidex (13, 2.5th percentile) were significant at lag 0 [relative risk (RR) = 1.145, 95 % confidence interval (CI): 1.041-1.259] to lag 2 (RR = 1.049, 95 % CI: 1.010-1.089). The cumulative lag effects of low humidex were significant at lag 0-0 (RR = 1.145, 95 % CI: 1.041-1.259) to lag 0-6 (RR = 1.258, 95 % CI: 1.010-1.567) and reached a maximum at lag 0-3 (RR = 1.330, 95 % CI: 1.113-1.590). High humidex (44, 97.5th percentile) was not associated with the risk of HF. Females and people over the age of 75 appeared to be more susceptible to low humidex. In addition, the adverse effects of low humidex were more pronounced in the cold season. The AF and AN of low humidex on HF admissions were 24.8 % (95 % CI: 10.2-37.1 %) and 1538, respectively. CONCLUSION: Low humidex was associated with an increased risk of HF admissions. The government should take timely measures to prevent people from being exposed to low humidex to effectively reduce HF admissions.