ribavirin + PEG-IFNalpha-2a (Copegus + Pegasys / Pegasys + Copegus / Pegasys/Copegus)

Correction: Postoperative adding-on phenomenon in Lenke 1A/B and 2A/B adolescent idiopathic scoliosis: risk factors and predictive index.

Zhang Hongqi H, Li Tao T, Zhang Gengming G, Deng Ang A et al.

Clean Synthesis of N-4-Alkylamino-7-chloroquinoline Cyclic Imides: Influence of Lipophilicity on Antibacterial and Ecotoxicological Properties.

Luz-Filho Agenor P AP, Silva Thais C TC, Silva Matheus B MB, Sousa Abraão P AP et al.

Motivated by the promising antimicrobial and ecotoxicological effects of 4-alkylamino-7-chloroquinoline and N-alkylphthalimide derivatives, these privileged nuclei were linked to investigate how lipophilicity influences antibacterial activity and ecotoxicity. For this purpose, seven 4-alkylamino-7-chloroquinolines (2a-g) were prepared, of which four were used as precursors (2a-d) and reacted with different anhydrides. Using a clean synthetic approach, 4-alkylamino-7-chloroquinoline-succinimides (3a-d) and -phthalimides (5a-d) were obtained in yields of 60%-99% after only filtration with distilled water. In vitro assays were performed to determine the minimum inhibitory/bactericidal concentration (MIC/MBC) against Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus mutans. Lipophilicity (log P) and toxicity were predicted using the pkCSM program. In vitro toxicity tests on Artemia salina larvae were used as an indicator of ecotoxicity. 4-Alkylamino-7-chloroquinolines (2b, 2f, 2g) revealed a moderate MIC of 156.25 µg·mL-1 against Gram-(-) and Gram-(+) bacteria, whose predicted toxicity does not pose a potential risk to human health. Results indicate a correlation between increased lipophilicity and higher ecotoxicity, where less lipophilic compounds were less toxic to A. salina (LC50 133.01-777.50 µg·mL-1) than 4-alkylamino-7-chloroquinoline-phthalimides, suggesting further investigation of their cytotoxicity.

Synergistic effects of berberine and adipose stem cells in a silk fibroin-PEG hydrogel for diabetic wound healing via macrophage polarization modulation.

Hu Xiaohao X, Xu Jia J, Zhong Yanping Y, Zheng Weihao W et al.

Diabetic wound repair remains a considerable clinical challenge, largely due to the limited efficacy of current therapies. Herein, we engineered a novel silk fibroin (SF)-polyethylene glycol (PEG) hydrogel (SPB) incorporated with berberine (BBR) and adipose-derived stem cells (ASCs) to synergistically promote diabetic wound healing. By optimizing the physicochemical properties of SPB, we found that a 7:3 SF:PEG ratio provided an ideal balance of pore size (25.83 ± 3.94 μm), mechanical strength (32.33 ± 4.07 kPa) and sustained BBR release. In vitro, SPB significantly enhanced ASC paracrine function, promoting the production of vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF-2), stromal cell-derived factor 1 (SDF-1), platelet-derived growth factor-BB (PDGF-BB), and transforming growth factor beta (TGF-β). Accordingly, SF-based hydrogel system (SPBA) markedly stimulated fibroblast proliferation and migration and enhanced endothelial cell angiogenesis. Moreover, SPBA effectively modulated macrophage repolarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype, thereby suppressing inflammation. In vivo, SPBA demonstrated remarkable therapeutic efficacy in diabetic rat full-thickness skin wounds, accelerating wound closure, promoting re-epithelialization, collagen deposition and neovascularization, while reducing local inflammation. These results highlight SPBA as a highly efficient and promising biomaterial strategy for diabetic wound treatment.

Dual Roles of RAD23b and RAD4 on the Desiccation Tolerance of Germinated Seeds.

Huang Xu X, Qi Manyao M, Ye Tiantian T, Chen Yang Y et al.

Desiccation tolerance (DT) is a survival trait enabling orthodox seeds to withstand extremely low water content. While some protective factors are characterised, it remains mechanistically obscure. Here, based on PEG-induced DT re-establishment in germinated Brassica napus L. seeds, we investigated the dual functions of nucleotide excision repair (NER) components RAD23b and RAD4 in DNA repair and transcriptional regulation of root development. PEG pre-treatment alleviated dehydration-induced DNA damage and activated NER genes, suggesting the involvement of NER in seed DT. Unexpectedly, Arabidopsis atrad23b mutant and BnRAD23b/BnRAD4 over-expressing seeds all exhibited significantly decreased DT after dry back, which evoked a hypothesis that BnRAD23b-BnRAD4 functions beyond NER. Normally, BnRAD4 interacted with BnRAD23b and repressed the expression of root development genes NAC103, EMB1444, RRA1 by directly binding to STRE elements within their promoters. Dehydration stress alleviated this repression, drove transcriptional reprogramming and might redirect the complex to execute DNA repair. Genetic analyses revealed that germinated seeds of atnac103, atemb1444, and atrra1 single mutants all exhibited reduced DT, and double mutants under atrad23b background almost abolished DT. This study suggests that RAD23b and RAD4 may regulate DT re-establishment of germinated seeds through balancing genome integrity and radicle development, with implications for DT study broadly.