RESUMO
Cellulose foams are considered an effective alternative to plastic foam, because of their advantages of low density, high porosity, low thermal conductivity, and renewable nature. However, they still suffer from complex processing, poor mechanical properties, and flammability. As an agricultural waste, bagasse is rich in cellulose, which has attracted much attention. Inspired by the fact that borate ions can effectively enhance the strength of plant tissue by their cross-linking with polysaccharides, the present work designs and fabricates a series of multifunctional bagasse foams with robust strength and improved thermal insulation and flame retardancy via a unique borax-induced self-assembly and atmospheric pressure drying route using bagasse as a raw material, borate as a cross-linking agent, and chitosan as an additive. As a result, the optimized foam exhibits a high porosity (93.5%), a high hydrophobic water contact angle (150.4°), a low thermal conductivity (63.4 mW/(m·K) at 25 °C), and an outstanding flame retardancy. The present study provides a novel and inspiring idea for large-scale production of cellulose foams through an environmentally friendly and cost-effective approach.
RESUMO
Insects rely on a family of seven transmembrane proteins called gustatory receptors (GRs) to encode different taste modalities, such as sweet and bitter. We report structures of Drosophila sweet taste receptors GR43a and GR64a in the apo and sugar-bound states. Both GRs form tetrameric sugar-gated cation channels composed of one central pore domain (PD) and four peripheral ligand-binding domains (LBDs). Whereas GR43a is specifically activated by the monosaccharide fructose that binds to a narrow pocket in LBDs, disaccharides sucrose and maltose selectively activate GR64a by binding to a larger and flatter pocket in LBDs. Sugar binding to LBDs induces local conformational changes, which are subsequently transferred to the PD to cause channel opening. Our studies reveal a structural basis for sugar recognition and activation of GRs.
Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Açúcares , Percepção Gustatória , Paladar , Animais , Paladar/fisiologia , Percepção Gustatória/fisiologia , Drosophila melanogaster/fisiologia , Proteínas de Drosophila/química , Conformação ProteicaRESUMO
Background: The synergistic effects of antiangiogenic inhibitor bevacizumab and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) therapy were encouraging in patients with EGFR-mutant advanced NSCLC, though some controversy remains. The specific subgroup of patients who might benefit most from the EGFR-TKI and bevacizumab combination therapy is yet to be determined. Methods: Randomized clinical trials (RCTs) that had compared the clinical efficacy of EGFR-TKI and bevacizumab combination therapy with EGFR-TKI monotherapy in treating EGFR-mutant advanced NSCLC patients published before 23 December 2022 were searched in the Cochrane, PubMed and Embase. We performed a meta-analysis for the overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events with a grade equal or more than 3 (grade≥3 TRAEs). Subgroup analyses of PFS and OS stratified by clinical characteristics and treatment were conducted. Results: We included 10 RCTs involving 1520 patients. Compared with EGFR-TKI monotherapy, addition of bevacizumab to EGFR-TKI resulted in a significantly higher PFS (hazard ratio (HR) = 0.74, 95% confidence interval (95% CI): 0.62-0.87)) and ORR (risk ratio (RR) = 1.07, 95% CI: 1.01-1.13). However, no significant difference in OS (HR = 0.96, 95% CI: 0.83-1.12) was noticed. Patients with EGFR-mutant advanced NSCLC receiving combination therapy showed PFS improvement regardless of gender (male or female), Eastern Cooperative Oncology Group performance status (0 or 1), baseline central nervous system (CNS) metastasis (presence or absence) and EGFR mutation type (19del or 21L858R). Subgroup analyses showed that, with the treatment of bevacizumab and EGFR-TKI, patients who ever smoked achieved significantly better OS and PFS benefits (HR = 0.68, 95% CI: 0.48-0.95; HR = 0.59, 95% CI: 0.46-0.74, respectively), and those aged <75 years and the Asian population had significantly prolonged PFS (HR = 0.69, 95% CI: 0.52-0.91; HR = 0.71, 95% CI: 0.58-0.87; respectively). The superiority of EGFR-TKI and bevacizumab combination therapy against EGFR-TKI monotherapy in improving PFS was more significant in the erlotinib regimen subgroup. The risk of grade≥3 TRAEs was remarkably higher in the combination therapy group (HR = 1.73, 95% CI: 1.39-2.16). Conclusion: Addition of bevacizumab to EGFR-TKI therapy provided significantly better PFS and ORR for EGFR-mutant advanced NSCLC patients, though with higher risk of grade≥3 TRAEs. Patients who ever smoked, aged <75 years, and Asian population might benefit more from the combination regimen. Systematic Review Registration: This systematic review and meta-analysis was registered in the PROSPERO database (CRD42023401926).