JOURNAL OF POLYMER SCIENCE
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2024
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IF 3.9
Mingjiao Li,Xinyi Chen,Qiyang Feng,Wanyi Fan,Yitong Ding,Ze Kan,Zhibo Li
Synthetic poly(4-hydroxybutyrate) (P4HB), a flexible and biodegradable polymer, shows great promise in improving the toughness of poly(lactic acid) (PLA), but the inherent immiscibility of PLA and P4HB compromises the toughening efficiency. To address this issue, P4HB grafted glycidyl methacrylate (P4HB-g-GMA) is synthesized for the purpose of enhancing the compatibility within the PLA/P4HB blend. The epoxy groups on P4HB-g-GMA can form strong chemical bonds with PLA chains and remain compatible with P4HB. Rheological data confirm that adding P4HB-g-GMA enhances polymer chain entanglement. Therefore, the phase interface of the blend becomes more diffuse, leading to improved mechanical performance. Specifically, a 3D-printed PLA/P4HB/P4HB-g-GMA blend containing 8% P4HB-g-GMA (PLA/P4HB/G8) achieves an elongation at break of 161.5%, approximately 22.7 times higher than that of a PLA/P4HB blend without the modifier. Moreover, the PLA/P4HB/G8 blends show a higher volume expansion ratio (VER) and better cell morphology due to the increased melt strength from P4HB-g-GMA. This study demonstrates a simple and efficient method to improve the compatibility between PLA and P4HB, resulting in superior mechanical performance of PLA/P4HB blends and broadening their potential applications in foaming. Graphical
研究领域:
材料科学
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高分子工程
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生物降解聚合物
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泡沫技术
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Xinyi Song,Haipeng Rao,Chunchun Huang,Miaoling Huang,Ying Ma,Jingyu Xin,Jiajia Hou,Zhigang Hu,Lingfeng He,Feiyan Pan,Lingdong Yang,Zhigang Guo
Fumarate hydratase (FH) catalyzes the conversion of fumarate to malate in the tricarboxylic acid cycle. Its deficiency leads to fumarate accumulation, which is associated with kidney cancer metastasis, though the exact mechanisms remain unclear. Here, we identify prolyl 4-hydroxylase beta (P4HB) as a novel fumarate target in FH-deficient cancer cells that promotes migration and invasion. FH knockdown in human renal cancer cells significantly enhanced migratory and invasive capacities by 10- and 8-fold, respectively. Mechanistically, fumarate-induced succination stabilizes P4HB, promoting type I collagen production and enhancing tumor metastasis. P4HB knockdown markedly suppresses FH deficiency-induced metastasis in xenograft models. Fluorescence intensity in the FH knockdown group was about 10-fold higher, and tumor-bearing liver weight was approximately 1.5-fold greater than that in the FH and P4HB co-knockdown group. These results underscore the pivotal role of P4HB in metastasis. Additionally, we reveal NDP52 as a specific autophagy receptor that recognizes and binds to P4HB, mediating its degradation through the autophagy-lysosome pathway. However, succination of P4HB disrupts this recognition, interaction, and degradation, stabilizing P4HB. Together, these findings provide new insights into how fumarate-mediated succination affects P4HB protein stability and cancer metastasis, and suggest that P4HB could serve as a potential therapeutic target in FH-deficient cancers.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
POLYMER DEGRADATION AND STABILITY
·
2024
·
IF 6.3
Yitong Ding,Mingjiao Li,Wenjing Dong,Ze Kan,Zhibo Li
Chemically synthesized poly(4-hydroxybutyrate) (P4HB) serves as an alternative material for toughening poly(lactic acid) (PLA), but the two materials exhibit poor compatibility, and most compatibilizers fail to localize at the phase interface, resulting in inefficient toughening. In this study, a phase interface-located reactive compatibilizer, poly (glycidyl methacrylate) (PGMA), is synthesized to enhance the interfacial adhesion between PLA and P4HB, thereby improving their compatibility. The PGMA compatibilizer demonstrates a tendency to selectively disperse at the phase interface of PLA and P4HB supported by thermodynamic calculations. Compared to the PLA/P4HB blend, the PLA/P4HB/PGMA blend exhibits enhanced molecular chain entanglement and a blurrier phase interface. Consequently, the mechanical and shape memory behavior of the PLA/P4HB/PGMA blend are improved. For example, the elongation at break of the PLA/P4HB/PGMA blend increased from 20.8 % to 265.1 %, marking an increase of 12.7 times compared to the PLA/P4HB blend. Due to its small molecular weight, the T o n e s e t (onset degradation temperature) of PGMA is only 180.3 °C. Fortunately, the T o n e s e t of the PLA/P4HB/PGMA system exceeds 220 °C after the chain expansion reaction, indicating a significant improvement in thermal stability. Thus, the phase interface-located chain expansion reaction offers an effective approach to improving the compatibility of PLA/P4HB blends while maintaining their high thermal stability.
研究领域:
材料科学
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高分子化学
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产品关联
DOI
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2023
·
IF 4.6
Xiuxia Sun,Qi Chen,Angelique A. Guan,Shuaishuai Yuan,Zhibo Li
Abdominal wall defect caused by surgical trauma, congenital rupture, or tumor resection may result in hernia formation or even death. Tension-free abdominal wall defect repair by using patches is the gold standard to solve such problems. However, adhesions following patch implantation remain one of the most challenging issues in surgical practice. The development of new kinds of barriers is key to addressing peritoneal adhesions and repairing abdominal wall defects. It is already well recognized that ideal barrier materials need to have good resistance to nonspecific protein adsorption, cell adhesion, and bacterial colonization for preventing the initial development of adhesion. Herein, electrospun poly(4-hydroxybutyrate) (P4HB) membranes infused with perfluorocarbon oil are used as physical barriers. The oil-infused P4HB membranes can greatly prevent protein attachment and reduce blood cell adhesion in vitro. It is further shown that the perfluorocarbon oil-infused P4HB membranes can reduce bacterial colonization. The in vivo study reveals that perfluoro(decahydronaphthalene)-infused P4HB membranes can significantly prevent peritoneal adhesions in the classic abdominal wall defects’ model and accelerate defect repair, as evidenced by gross examination and histological evaluation. This work provides a safe fluorinated lubricant-impregnated P4HB physical barrier to inhibit the formation of postoperative peritoneal adhesions and efficiently repair soft-tissue defects.
研究领域:
生物医学工程
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材料科学
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外科实践
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组织工程
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生物材料
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
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2026
·Vol. 45
·期 1
·153
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IF 14.3
Wang Lifen,Xu Hongxia,Liu Tianyu,Zhu Dongliang,Chen Liping,Liu Tzu-ming,Lin Shuhai,Liu Xueyi,Feng Hao,Wang Li,Di Li-jun
Background Triple-negative breast cancer (TNBC) is characterized by aggressive clinical behaviour and frequent resistance to chemotherapy. While ferroptosis—an iron-dependent form of cell death driven by lipid peroxidation—holds promise as a therapeutic strategy, its efficacy is often limited by adaptive resistance mechanisms that remain incompletely understood. C-terminal binding protein (CtBP) is an oncogene associated with poor prognosis in TNBC; however, whether CtBP confers resistance to oxidative stress and ferroptosis, thereby contributing to its oncogenic function, remains unknown. Methods We utilized both in vitro cell lines and in vivo mouse models to investigate the role of CtBP in regulating oxidative stress and ferroptosis sensitivity. Integrative analyses, including transcriptomics, metabolomics, and clinical data interrogation, were employed to elucidate the mechanisms underlying CtBP-mediated resistance. Key mechanistic findings were further validated in clinical TNBC specimens using protein correlation analysis. Results We identified CtBP as a stress-inducible gene that is essential for ferroptosis resistance in TNBC. Mechanistically, CtBP promotes resistance by transcriptionally upregulating Prolyl 4-Hydroxylase Subunit Beta (P4HB). P4HB, localized to the endoplasmic reticulum (ER), functions as a chaperone to facilitate the correct folding and membrane maturation of SLC7A11, the catalytic subunit of the system xc - cystine/glutamate antiporter pivotal for glutathione (GSH) biosynthesis. We demonstrated that P4HB-mediated SLC7A11 maturation relies on its disulfide isomerase activity and ER retention signal (KDEL). Depletion of either CtBP or P4HB impaired SLC7A11 membrane trafficking, lead to accumulation of lipid peroxides and sensitization to ferroptosis. Conversely, P4HB overexpression restored SLC7A11 function and ferroptosis resistance in CtBP-deficient cells. Furthermore, significant positive correlations among CtBP, P4HB, and SLC7A11 expressions in clinical samples underscore the critical role of CtBP/P4HB/SLC7A11 axis in driving cancer aggressiveness. In vivo, targeting the CtBP/P4HB/SLC7A11 axis sensitized TNBC xenografts to the ferroptosis inducer RSL3, significantly suppressing tumor growth and lung metastasis. Conclusions This study identifies the CtBP/P4HB/SLC7A11 axis as a critical mediator of ferroptosis resistance in TNBC. These findings highlight this pathway as a potent therapeutic target to overcome resistance and enhance the efficacy of ferroptosis-inducing regimens in TNBC treatment.
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DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Xinyi Chen,Sisi Tian,Yiwei Fu,Wanyi Fan,Xiaobei Liu,Yitong Ding,Ze Kan
Owing to inherent issues like interfacial stress concentration, open-cell, a low volume expansion ratio ( VER ) and cell density, the impact resistance and thermal insulation of supercritical foamed poly(lactic acid) (PLA) blend foams remain unsatisfactory. To overcome these challenges, an in-situ cross-linking strategy is employed to enhance the compatibility between PLA and poly(4-hydroxybutyrate) (P4HB), while improving the melt strength and crystallization behavior of the blends. The modified PLA/P4HB blend exhibits a blurred interfacial boundary with fewer stress concentrations. As a result, the specific impact strength increases from 9.76 to 26.17 kJ·m −2 /(g·cm −3 ) after foaming. The ambiguous interface and enhanced melt strength reduce the risk of cell wall rupture and collapse, while the increased crystallization provides additional nucleation sites. Consequently, the modified PLA/P4HB foam transitions from an open-cell to a closed-cell structure, achieving a VER of 35.4 and a cell density of 2.0 × 10 7 cells/cm 3 , representing respective increases of 16.1-fold and 9.1-fold compared to unmodified PLA/P4HB foam. At this time, the thermal conductivity and thermal diffusivity of the PLA/P4HB foam reach 31.5 mW/m·K and 8.1 × 10 −7 m 2 /s, respectively. In conclusion, this strategy provides a method for producing PLA/P4HB foams with high impact resistance and thermal insulation, and addresses common issues associated with PLA-based blends foam.
研究领域:
材料科学
·
高分子化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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