首页 > 最新文献

工程技术最新文献

英文 中文
IF:
Genetic algorithm-optimized artificial neural network for multi-objective optimization of biomass and exopolysaccharide production by Haloferax mediterranei.
IF 3.5 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-05-01 Epub Date: 2025-03-22 DOI: 10.1007/s00449-025-03143-3
Alaa M Al Rawahi, Mohd Zafar, Taqi Ahmed Khan, Sara Al Araimi, Biswanath Mahanty, Shishir Kumar Behera

Microbial production of industrially important exopolysaccharide (EPS) from extremophiles has several advantages. In this study, key media components (i.e., sucrose, yeast extract, and urea) were optimized for biomass growth and extracellular EPS production in Haloferax mediterranei DSM 1411 using Box-Behnken design. In a multi-objective optimization framework, response surface methodology (RSM) and genetic algorithm (GA)-optimized artificial neural network (ANN) were used to minimize biomass growth while increasing EPS production. The performance of the selected ANN model for the prediction of biomass and EPS (R2: 0.964 and 0.975, respectively) was found to be better than that of the multiple regression model (R2: 0.818, 0.963, respectively). The main effect of sucrose and its interaction with urea appears to have a significant effect on both responses. The ANN model projects an increase in EPS production from 4.49 to 18.2 g l-1 while shifting the priority from biomass to biopolymer. The optimized condition predicted a maximum biomass and EPS production of 17.27 g l-1 and 17.80 g l-1, respectively, at concentrations of sucrose (19.98 g l-1), yeast extract (1.97 g l-1), and urea (1.99 g l-1). Based on multi-objective optimization, the GA-ANN model predicted an increase in the EPS to biomass ratio for increasing the EPS and associated biomass production. The extracted EPS, identified as Gellan gum through NMR spectroscopy, was further characterized for surface and elemental composition using SEM-EDX analysis.

利用嗜极微生物生产工业上重要的外多糖(EPS)具有多种优势。在本研究中,采用盒-贝肯设计(Box-Behnken design)对关键培养基成分(即蔗糖、酵母提取物和尿素)进行了优化,以促进Haloferax mediterranei DSM 1411的生物量生长和胞外多糖生产。在多目标优化框架中,采用了响应面方法学(RSM)和遗传算法(GA)优化的人工神经网络(ANN),以在提高 EPS 产量的同时尽量减少生物量的增长。结果发现,所选人工神经网络模型在预测生物量和 EPS 方面的性能(R2 分别为 0.964 和 0.975)优于多元回归模型(R2 分别为 0.818 和 0.963)。蔗糖的主效应及其与尿素的交互作用似乎对两种反应都有显著影响。ANN 模型预测 EPS 产量将从 4.49 克升至 18.2 克升至 1 克,同时优先考虑的因素从生物量转向生物聚合物。在蔗糖(19.98 克升-1)、酵母提取物(1.97 克升-1)和尿素(1.99 克升-1)浓度下,优化条件预测的最大生物量和 EPS 产量分别为 17.27 克升-1 和 17.80 克升-1。基于多目标优化,GA-ANN 模型预测了 EPS 与生物量的比率,以提高 EPS 和相关生物量的产量。提取的 EPS 通过核磁共振光谱鉴定为结冷胶,并通过 SEM-EDX 分析进一步确定了其表面和元素组成。
{"title":"Genetic algorithm-optimized artificial neural network for multi-objective optimization of biomass and exopolysaccharide production by Haloferax mediterranei.","authors":"Alaa M Al Rawahi, Mohd Zafar, Taqi Ahmed Khan, Sara Al Araimi, Biswanath Mahanty, Shishir Kumar Behera","doi":"10.1007/s00449-025-03143-3","DOIUrl":"10.1007/s00449-025-03143-3","url":null,"abstract":"<p><p>Microbial production of industrially important exopolysaccharide (EPS) from extremophiles has several advantages. In this study, key media components (i.e., sucrose, yeast extract, and urea) were optimized for biomass growth and extracellular EPS production in Haloferax mediterranei DSM 1411 using Box-Behnken design. In a multi-objective optimization framework, response surface methodology (RSM) and genetic algorithm (GA)-optimized artificial neural network (ANN) were used to minimize biomass growth while increasing EPS production. The performance of the selected ANN model for the prediction of biomass and EPS (R<sup>2</sup>: 0.964 and 0.975, respectively) was found to be better than that of the multiple regression model (R<sup>2</sup>: 0.818, 0.963, respectively). The main effect of sucrose and its interaction with urea appears to have a significant effect on both responses. The ANN model projects an increase in EPS production from 4.49 to 18.2 g l<sup>-1</sup> while shifting the priority from biomass to biopolymer. The optimized condition predicted a maximum biomass and EPS production of 17.27 g l<sup>-1</sup> and 17.80 g l<sup>-1</sup>, respectively, at concentrations of sucrose (19.98 g l<sup>-1</sup>), yeast extract (1.97 g l<sup>-1</sup>), and urea (1.99 g l<sup>-1</sup>). Based on multi-objective optimization, the GA-ANN model predicted an increase in the EPS to biomass ratio for increasing the EPS and associated biomass production. The extracted EPS, identified as Gellan gum through NMR spectroscopy, was further characterized for surface and elemental composition using SEM-EDX analysis.</p>","PeriodicalId":9024,"journal":{"name":"Bioprocess and Biosystems Engineering","volume":" ","pages":"785-798"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficient enzymatic hydrolysis of sweet potato residue by fed-batch method to prepare high- concentration glucose.
IF 3.5 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-05-01 Epub Date: 2025-03-25 DOI: 10.1007/s00449-025-03146-0
Shaoyu Wang, Jialong Xu, Shuai Xu, Yuxiang Li, Zhongbo Sun, Dahai Li, Yaohong Ma, Juanjuan Qian, Liping Tan, Tongjun Liu

China is the largest producer and exporter of sweet potato in the world. Sweet potato residue (SPR) separated after starch extraction account for more than 10% of the total dry matter of sweet potatoes. However, large amounts of unutilized SPR can cause environmental pollution. SPR is rich in starch and cellulose, both of which can be converted into glucose, making it a good carbon source for microbial fermentation. Therefore, an efficient SPR enzymatic process needs to be developed. The technological conditions of high-solid enzymatic hydrolysis of SPR by fed-batch was investigated in detail. Cellulase, amylase, and pectinase had synergistic effects on SPR enzymatic digestion. The experiments were first conducted to optimize the total enzyme addition of 15 mg enzyme protein/g substrate. The experiments were designed using Design-Expert (10.0) to optimize the enzyme proportions to 42%, 31.8%, and 26.2% for cellulase, amylase, and pectinase, respectively. The fed-batch enzymatic hydrolysis of SPR was investigated. The feed time and amount were optimized. The results showed that the initial SPR enzymatic hydrolysis concentration was 14% (w/v), 9% (w/v) was added at 3 h, 6 h and 12 h, respectively and the final substrate concentration was 41% (w/v). After 24 h of enzymatic hydrolysis, the glucose concentration obtained was 194.57 g/L and the glucan conversion was 63.58%. The fed-batch enzymatic hydrolysis of SPR described in this study has great potential for the whole chain utilization of sweet potato and in the microbial fermentation industry as it is environmentally friendly, economical and efficient.

{"title":"Efficient enzymatic hydrolysis of sweet potato residue by fed-batch method to prepare high- concentration glucose.","authors":"Shaoyu Wang, Jialong Xu, Shuai Xu, Yuxiang Li, Zhongbo Sun, Dahai Li, Yaohong Ma, Juanjuan Qian, Liping Tan, Tongjun Liu","doi":"10.1007/s00449-025-03146-0","DOIUrl":"10.1007/s00449-025-03146-0","url":null,"abstract":"<p><p>China is the largest producer and exporter of sweet potato in the world. Sweet potato residue (SPR) separated after starch extraction account for more than 10% of the total dry matter of sweet potatoes. However, large amounts of unutilized SPR can cause environmental pollution. SPR is rich in starch and cellulose, both of which can be converted into glucose, making it a good carbon source for microbial fermentation. Therefore, an efficient SPR enzymatic process needs to be developed. The technological conditions of high-solid enzymatic hydrolysis of SPR by fed-batch was investigated in detail. Cellulase, amylase, and pectinase had synergistic effects on SPR enzymatic digestion. The experiments were first conducted to optimize the total enzyme addition of 15 mg enzyme protein/g substrate. The experiments were designed using Design-Expert (10.0) to optimize the enzyme proportions to 42%, 31.8%, and 26.2% for cellulase, amylase, and pectinase, respectively. The fed-batch enzymatic hydrolysis of SPR was investigated. The feed time and amount were optimized. The results showed that the initial SPR enzymatic hydrolysis concentration was 14% (w/v), 9% (w/v) was added at 3 h, 6 h and 12 h, respectively and the final substrate concentration was 41% (w/v). After 24 h of enzymatic hydrolysis, the glucose concentration obtained was 194.57 g/L and the glucan conversion was 63.58%. The fed-batch enzymatic hydrolysis of SPR described in this study has great potential for the whole chain utilization of sweet potato and in the microbial fermentation industry as it is environmentally friendly, economical and efficient.</p>","PeriodicalId":9024,"journal":{"name":"Bioprocess and Biosystems Engineering","volume":" ","pages":"829-839"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Environmental bioremediation of pharmaceutical residues: microbial processes and technological innovations: a review. 药物残留的环境生物修复:微生物过程和技术创新:综述。
IF 3.5 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-05-01 Epub Date: 2025-01-06 DOI: 10.1007/s00449-024-03125-x
Upeksha Gayangani Jayasekara, Tony Hadibarata, Dwi Hindarti, Budi Kurniawan, Mohammad Noor Hazwan Jusoh, Paran Gani, Inn Shi Tan, Adhi Yuniarto, Rubiyatno, Mohd Hairul Bin Khamidun

The ubiquitous presence of pharmaceuticals and personal care products (PPCPs) in the environment has become a significant concern due to their persistence, bioaccumulation potential in biota, and diverse implications for human health and wildlife. This review provides an overview of the current state-of-the-art in environmental bioremediation techniques for reducing pharmaceutical residues, with a special emphasis on microbial physiological aspects. Numerous microorganisms, including algae, bacteria or fungi, can biodegrade various pharmaceutical compounds such as antibiotics, analgesics and beta-blockers. Some microorganisms are capable of transferring electrons within the cell, and this feature can be harnessed using Bio Electrochemical Systems (BES) to potentiate the degradation of pharmaceuticals present in wastewater. Moreover, researchers are evaluating the genetic modification of microbial strains to improve their degradation capacity and expand list of target compounds. This includes also discuss how environment changes, such as fluctuations in temperature or pH, may affect bioremediation efficiency. Furthermore, the presence of pharmaceuticals in the environment is emphasised as a major public health issue because it increases the chance for antibiotic-resistant bacteria emerging. This review combines existing information and outlines needed research areas for improving bioremediation technologies in the future.

由于药物和个人护理产品的持久性、在生物群中的生物积累潜力以及对人类健康和野生动物的各种影响,它们在环境中无处不在的存在已成为一个重大问题。本文综述了目前用于减少药物残留的环境生物修复技术的最新进展,特别强调了微生物生理方面的研究。许多微生物,包括藻类、细菌或真菌,可以生物降解各种药物化合物,如抗生素、镇痛药和-受体阻滞剂。一些微生物能够在细胞内转移电子,这一特性可以利用生物电化学系统(BES)来增强废水中药物的降解。此外,研究人员正在评估微生物菌株的基因改造,以提高它们的降解能力和扩大目标化合物的清单。这也包括讨论环境变化,如温度或pH值的波动,如何影响生物修复效率。此外,环境中药物的存在被强调为一个主要的公共卫生问题,因为它增加了耐抗生素细菌出现的机会。这篇综述结合了现有信息并概述了未来改进生物修复技术所需的研究领域。
{"title":"Environmental bioremediation of pharmaceutical residues: microbial processes and technological innovations: a review.","authors":"Upeksha Gayangani Jayasekara, Tony Hadibarata, Dwi Hindarti, Budi Kurniawan, Mohammad Noor Hazwan Jusoh, Paran Gani, Inn Shi Tan, Adhi Yuniarto, Rubiyatno, Mohd Hairul Bin Khamidun","doi":"10.1007/s00449-024-03125-x","DOIUrl":"10.1007/s00449-024-03125-x","url":null,"abstract":"<p><p>The ubiquitous presence of pharmaceuticals and personal care products (PPCPs) in the environment has become a significant concern due to their persistence, bioaccumulation potential in biota, and diverse implications for human health and wildlife. This review provides an overview of the current state-of-the-art in environmental bioremediation techniques for reducing pharmaceutical residues, with a special emphasis on microbial physiological aspects. Numerous microorganisms, including algae, bacteria or fungi, can biodegrade various pharmaceutical compounds such as antibiotics, analgesics and beta-blockers. Some microorganisms are capable of transferring electrons within the cell, and this feature can be harnessed using Bio Electrochemical Systems (BES) to potentiate the degradation of pharmaceuticals present in wastewater. Moreover, researchers are evaluating the genetic modification of microbial strains to improve their degradation capacity and expand list of target compounds. This includes also discuss how environment changes, such as fluctuations in temperature or pH, may affect bioremediation efficiency. Furthermore, the presence of pharmaceuticals in the environment is emphasised as a major public health issue because it increases the chance for antibiotic-resistant bacteria emerging. This review combines existing information and outlines needed research areas for improving bioremediation technologies in the future.</p>","PeriodicalId":9024,"journal":{"name":"Bioprocess and Biosystems Engineering","volume":" ","pages":"705-723"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In situ synthesis of silver nanoparticles on silk: producing antibacterial fabrics.
IF 3.5 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-05-01 Epub Date: 2025-03-03 DOI: 10.1007/s00449-025-03138-0
Xiao-Qian Jin, Jia-Lei Li, Jie Liu, Liang-Liang Chen, Chan Liu, Ya-Qing Zhou, Wen-Pu Shi, Huan Liang, Wei-Hong Guo, Da-Chuan Yin

Herein, we explored an effective method for preparing silver nanoparticles (Ag NPs)-coated antibacterial silk fabrics. In particular, using amino acids and cellulose from silk as reducing agents and silver nitrate as a precursor, Ag NPs were synthesised in situ on the surface of silk without requiring additional reducing agents and catalysts. The surface morphology and chemical composition of the involved samples were characterised using techniques such as scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy. Notably, silk and silk precursors (silkworm cocoons, silk fibers and sericin) could be used for in situ Ag NPs synthesis. Furthermore, the antibacterial properties of the samples were evaluated against Escherichia coli-a Gram-negative bacterium-as a model, demonstrating an impressive antibacterial rate of up to 99.91%. In addition, we investigated the water absorption behaviour of the samples at 25 °C by assessing their moisture regain, water retention value and vertical wick height. The results indicated that the Ag NPs coating did not damage the water absorption performance of the involved silk. Finally, we compared the fabric performance before and after treatment using a universal testing machine and colorimeter. The results showed that the mechanical properties of the fabrics with the Ag NPs coating did not substantially change with treatment, but the fabrics became more yellowish. Overall, this research has notable application potential in the field of antibacterial fabrics.

{"title":"In situ synthesis of silver nanoparticles on silk: producing antibacterial fabrics.","authors":"Xiao-Qian Jin, Jia-Lei Li, Jie Liu, Liang-Liang Chen, Chan Liu, Ya-Qing Zhou, Wen-Pu Shi, Huan Liang, Wei-Hong Guo, Da-Chuan Yin","doi":"10.1007/s00449-025-03138-0","DOIUrl":"10.1007/s00449-025-03138-0","url":null,"abstract":"<p><p>Herein, we explored an effective method for preparing silver nanoparticles (Ag NPs)-coated antibacterial silk fabrics. In particular, using amino acids and cellulose from silk as reducing agents and silver nitrate as a precursor, Ag NPs were synthesised in situ on the surface of silk without requiring additional reducing agents and catalysts. The surface morphology and chemical composition of the involved samples were characterised using techniques such as scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy. Notably, silk and silk precursors (silkworm cocoons, silk fibers and sericin) could be used for in situ Ag NPs synthesis. Furthermore, the antibacterial properties of the samples were evaluated against Escherichia coli-a Gram-negative bacterium-as a model, demonstrating an impressive antibacterial rate of up to 99.91%. In addition, we investigated the water absorption behaviour of the samples at 25 °C by assessing their moisture regain, water retention value and vertical wick height. The results indicated that the Ag NPs coating did not damage the water absorption performance of the involved silk. Finally, we compared the fabric performance before and after treatment using a universal testing machine and colorimeter. The results showed that the mechanical properties of the fabrics with the Ag NPs coating did not substantially change with treatment, but the fabrics became more yellowish. Overall, this research has notable application potential in the field of antibacterial fabrics.</p>","PeriodicalId":9024,"journal":{"name":"Bioprocess and Biosystems Engineering","volume":" ","pages":"725-736"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hybrid dynamic flux balance modeling approach for bioprocesses: an E. coli case study.
IF 3.5 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-05-01 Epub Date: 2025-03-25 DOI: 10.1007/s00449-025-03147-z
Zahra Negahban, Valerie Ward, Anne Richelle, Chris McCready, Hector Budman

In this study, we present a hybrid dynamic flux balance analysis (DFBA) model, combined with Partial Least Squares (PLS) regression, to simulate cell culture behavior in response to variations in media composition. DFBA models typically incorporate a stoichiometric matrix representing metabolic reactions, leveraging the pseudo-stationarity assumption to reduce the number of parameters, which in turn minimizes the risk of overfitting. Here, PLS regression is employed to define kinetic rate constraints within the DFBA model, capturing the dynamic and non-linear nature of reaction rates over different culture phases. An optimization approach identifies the minimal number of kinetic constraints required, ensuring model accuracy without excessive complexity. Our hybrid model is validated through simulation case studies using an E. coli system, demonstrating its effectiveness in adjusting to changes in initial media composition. The case studies reveal that the model's accuracy improves with a more detailed stoichiometric matrix, particularly when larger networks or more varied metabolic environments are present. Additionally, the hybrid DFBA-PLS approach provides a robust and scalable modeling framework adaptable to other bioprocesses, offering insights into medium composition effects and highlighting its potential for bioprocess optimization.

在这项研究中,我们提出了一种混合动态通量平衡分析(DFBA)模型,结合偏最小二乘法(PLS)回归,模拟细胞培养行为对培养基成分变化的响应。动态通量平衡分析模型通常包含一个代表代谢反应的化学计量矩阵,利用伪静态假设来减少参数数量,从而将过度拟合的风险降至最低。在此,采用 PLS 回归法在 DFBA 模型中定义动力学速率约束,捕捉不同培养阶段反应速率的动态和非线性性质。通过优化方法确定了所需动力学约束的最小数量,从而确保了模型的准确性,同时又不会过于复杂。通过使用大肠杆菌系统进行模拟案例研究,验证了我们的混合模型在适应初始培养基成分变化方面的有效性。案例研究表明,随着化学计量矩阵更加详细,模型的准确性也会提高,尤其是当存在更大的网络或更多样的代谢环境时。此外,DFBA-PLS 混合方法提供了一个稳健且可扩展的建模框架,可适用于其他生物过程,提供了对培养基组成影响的见解,并突出了其在生物过程优化方面的潜力。
{"title":"Hybrid dynamic flux balance modeling approach for bioprocesses: an E. coli case study.","authors":"Zahra Negahban, Valerie Ward, Anne Richelle, Chris McCready, Hector Budman","doi":"10.1007/s00449-025-03147-z","DOIUrl":"10.1007/s00449-025-03147-z","url":null,"abstract":"<p><p>In this study, we present a hybrid dynamic flux balance analysis (DFBA) model, combined with Partial Least Squares (PLS) regression, to simulate cell culture behavior in response to variations in media composition. DFBA models typically incorporate a stoichiometric matrix representing metabolic reactions, leveraging the pseudo-stationarity assumption to reduce the number of parameters, which in turn minimizes the risk of overfitting. Here, PLS regression is employed to define kinetic rate constraints within the DFBA model, capturing the dynamic and non-linear nature of reaction rates over different culture phases. An optimization approach identifies the minimal number of kinetic constraints required, ensuring model accuracy without excessive complexity. Our hybrid model is validated through simulation case studies using an E. coli system, demonstrating its effectiveness in adjusting to changes in initial media composition. The case studies reveal that the model's accuracy improves with a more detailed stoichiometric matrix, particularly when larger networks or more varied metabolic environments are present. Additionally, the hybrid DFBA-PLS approach provides a robust and scalable modeling framework adaptable to other bioprocesses, offering insights into medium composition effects and highlighting its potential for bioprocess optimization.</p>","PeriodicalId":9024,"journal":{"name":"Bioprocess and Biosystems Engineering","volume":" ","pages":"841-856"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Peptides-functionalized gold nanostars enhanced degradation of PD-L1 for improved prostate cancer immunotherapy.
IF 2.3 4区 医学 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2025-05-01 Epub Date: 2025-02-24 DOI: 10.1177/08853282251319473
Liangjun Tao, Yifei Zhang, Jingwei Zhang, Jianping Tao, Yu Gong, Jun Mao, Qixing Tian, Ping Ao, Dong Zhuo

Blockage of the interaction between programmed death receptor-1 (PD-1) and programmed death ligand-1 (PD-L1) can restore T-cell activity and enhance antitumor immunity. PD-1/PD-L1 pathway inhibitors have promising applications in the treatment of advanced prostate cancer (PCa). We successfully developed a peptides-functionalized gold nanoconstruct (P-AuNS) consisted of PD-L1-binding peptide (PD-L1pep, P) and gold nanostar (AuNS), which could bind to cell-surface PD-L1 specifically and deliver PD-L1 into PCa cells with high efficiency. In PCa cells, P-AuNS can efficiently degrade PD-L1 in a lysosomal-dependent manner. In the co-culture system of Jurkat cells and DU145 cells, P-AuNS restored the proliferative capacity and interferon-gamma (IFN-γ) secretion level of Jurkat cells inhibited by co-cultured DU145 cells, indicating that P-AuNS effectively hampered the interaction between PD-1 and PD-L1. In addition, in PCa-bearing mice, P-AuNS can effectively inhibit tumor growth and down-regulate PD-L1 protein levels, and in vivo experimental results show that P-AuNS has no systemic toxicity. P-AuNS block the interaction between PD-1 and PD-L1 by efficiently degrading PD-L1, thus restoring the antitumor activity of T cells and inhibiting tumor progression of PCa. In all, P-AuNS has great promise as a potential immunotherapy strategy in the treatment of advanced PCa and even other solid tumors.

{"title":"Peptides-functionalized gold nanostars enhanced degradation of PD-L1 for improved prostate cancer immunotherapy.","authors":"Liangjun Tao, Yifei Zhang, Jingwei Zhang, Jianping Tao, Yu Gong, Jun Mao, Qixing Tian, Ping Ao, Dong Zhuo","doi":"10.1177/08853282251319473","DOIUrl":"10.1177/08853282251319473","url":null,"abstract":"<p><p>Blockage of the interaction between programmed death receptor-1 (PD-1) and programmed death ligand-1 (PD-L1) can restore T-cell activity and enhance antitumor immunity. PD-1/PD-L1 pathway inhibitors have promising applications in the treatment of advanced prostate cancer (PCa). We successfully developed a peptides-functionalized gold nanoconstruct (P-AuNS) consisted of PD-L1-binding peptide (PD-L1pep, P) and gold nanostar (AuNS), which could bind to cell-surface PD-L1 specifically and deliver PD-L1 into PCa cells with high efficiency. In PCa cells, P-AuNS can efficiently degrade PD-L1 in a lysosomal-dependent manner. In the co-culture system of Jurkat cells and DU145 cells, P-AuNS restored the proliferative capacity and interferon-gamma (IFN-γ) secretion level of Jurkat cells inhibited by co-cultured DU145 cells, indicating that P-AuNS effectively hampered the interaction between PD-1 and PD-L1. In addition, in PCa-bearing mice, P-AuNS can effectively inhibit tumor growth and down-regulate PD-L1 protein levels, and in vivo experimental results show that P-AuNS has no systemic toxicity. P-AuNS block the interaction between PD-1 and PD-L1 by efficiently degrading PD-L1, thus restoring the antitumor activity of T cells and inhibiting tumor progression of PCa. In all, P-AuNS has great promise as a potential immunotherapy strategy in the treatment of advanced PCa and even other solid tumors.</p>","PeriodicalId":15138,"journal":{"name":"Journal of Biomaterials Applications","volume":" ","pages":"1188-1201"},"PeriodicalIF":2.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A tandem conversion process for the synthesis of polyitaconic acid from glucose in the Aspergillus terreus culture.
IF 3.5 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-05-01 Epub Date: 2025-03-11 DOI: 10.1007/s00449-025-03139-z
Ikumi Kinoshita, Tomonari Tanaka, Yuji Aso

In this study, a bio-based vinylidene monomer, itaconic acid (IA), produced by a fungus Aspergillus terreus NBRC 6123 was polymerized in the culture. The inhibition of IA polymerization by the culture components was eased by extraction with 4-methyltetrahydropyran (4mTHP). The extraction with 4mTHP for 4 days under aerobic condition resulted in IA production at 67.9 g/L (522 mM) in the organic phase from 180 g/L glucose. Interestingly, 4mTHP did not affect to the glucose consumption and respiration of A. terreus. IA polymerization in 4mTHP for 72 h using 400 mM IA and 1 mM 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile) as a radical initiator under anaerobic condition by N2 gas purging resulted in that the IA conversion, and the weight-averaged molecular weight (Mw) and the molecular weight distribution (MWD) of the synthesized polyitaconic acid (polyIA) were 11.5%, 79.8 × 103 g/mol, and 1.26, respectively. The respiration by the IA producer itself was used to remove the residual oxygen in the flask by sealing after the IA production. Colorimetric evaluation with a redox indicator, resazurin, revealed that an anaerobic condition which is suitable for the IA polymerization can be accomplished by just incubation for 1 day after the sealing. The synthesis of polyIA from glucose in the same flask with 4mTHP was demonstrated, resulting in that the IA conversion, and Mw and MWD of the synthesized polyIA were 13.8%, 9.1 × 103 g/mol, and 1.24, respectively, when 47.1 g/L (362 mM) IA was produced by the extraction for 3 days. To our knowledge, this is the first demonstration of radical polymerization of vinylidene monomer in microbial cultures.

{"title":"A tandem conversion process for the synthesis of polyitaconic acid from glucose in the Aspergillus terreus culture.","authors":"Ikumi Kinoshita, Tomonari Tanaka, Yuji Aso","doi":"10.1007/s00449-025-03139-z","DOIUrl":"10.1007/s00449-025-03139-z","url":null,"abstract":"<p><p>In this study, a bio-based vinylidene monomer, itaconic acid (IA), produced by a fungus Aspergillus terreus NBRC 6123 was polymerized in the culture. The inhibition of IA polymerization by the culture components was eased by extraction with 4-methyltetrahydropyran (4mTHP). The extraction with 4mTHP for 4 days under aerobic condition resulted in IA production at 67.9 g/L (522 mM) in the organic phase from 180 g/L glucose. Interestingly, 4mTHP did not affect to the glucose consumption and respiration of A. terreus. IA polymerization in 4mTHP for 72 h using 400 mM IA and 1 mM 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile) as a radical initiator under anaerobic condition by N<sub>2</sub> gas purging resulted in that the IA conversion, and the weight-averaged molecular weight (Mw) and the molecular weight distribution (MWD) of the synthesized polyitaconic acid (polyIA) were 11.5%, 79.8 × 10<sup>3</sup> g/mol, and 1.26, respectively. The respiration by the IA producer itself was used to remove the residual oxygen in the flask by sealing after the IA production. Colorimetric evaluation with a redox indicator, resazurin, revealed that an anaerobic condition which is suitable for the IA polymerization can be accomplished by just incubation for 1 day after the sealing. The synthesis of polyIA from glucose in the same flask with 4mTHP was demonstrated, resulting in that the IA conversion, and Mw and MWD of the synthesized polyIA were 13.8%, 9.1 × 10<sup>3</sup> g/mol, and 1.24, respectively, when 47.1 g/L (362 mM) IA was produced by the extraction for 3 days. To our knowledge, this is the first demonstration of radical polymerization of vinylidene monomer in microbial cultures.</p>","PeriodicalId":9024,"journal":{"name":"Bioprocess and Biosystems Engineering","volume":" ","pages":"737-748"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
High α-lipoic acid-loaded hollow mesoporous prussian blue nanozymes for targeted therapy of nasopharyngeal carcinoma in mice.
IF 2.3 4区 医学 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2025-05-01 Epub Date: 2025-02-05 DOI: 10.1177/08853282251318514
Ya Pan, Xiaofeng Wang, Xuejun Zhou, Haipeng Chen, Yuxia Zou

This study successfully constructs a tumor-targeting α-lipoic acid-loaded hollow mesoporous prussian blue nanozyme (AHPRzyme) for targeted therapy of nasopharyngeal carcinoma in mice. In these nanozymes, Arg-Gly-Asp (RGD) acts as a targeting ligand, enabling effective targeting of tumor cells. Additionally, AHPRzyme exhibits multiple anti-tumor mechanisms: ① The prussian blue nanozymes in AHPRzyme have catalase (CAT) activity, which decomposes H2O2 in human nasopharyngeal carcinoma CEN2 cells into non-toxic H2O, reducing H2O2 levels and minimizing damage to normal cells. The released O2 helps alleviate the hypoxic environment of the tumor, inhibiting lactate production due to hypoxia and consequently suppressing tumor growth. ② The prussian blue nanozymes also have peroxidase (POD) activity, which catalyzes H2O2 in tumor cells to generate ·OH, a reactive oxygen species, leading to tumor cell apoptosis. ③ The α-lipoic acid structure in AHPRzyme contains disulfide bonds that react with GSH, depleting excess glutathione (GSH) in tumor cells, disrupting the oxidative stress balance within the cells, and making them more sensitive to reactive oxygen species, thereby increasing tumor cell apoptosis. In summary, AHPRzyme can inhibit tumor cell growth and promote tumor cell apoptosis by improving the tumor microenvironment, achieving the goal of anti-nasopharyngeal carcinoma therapy.

{"title":"High α-lipoic acid-loaded hollow mesoporous prussian blue nanozymes for targeted therapy of nasopharyngeal carcinoma in mice.","authors":"Ya Pan, Xiaofeng Wang, Xuejun Zhou, Haipeng Chen, Yuxia Zou","doi":"10.1177/08853282251318514","DOIUrl":"10.1177/08853282251318514","url":null,"abstract":"<p><p>This study successfully constructs a tumor-targeting α-lipoic acid-loaded hollow mesoporous prussian blue nanozyme (AHPRzyme) for targeted therapy of nasopharyngeal carcinoma in mice. In these nanozymes, Arg-Gly-Asp (RGD) acts as a targeting ligand, enabling effective targeting of tumor cells. Additionally, AHPRzyme exhibits multiple anti-tumor mechanisms: ① The prussian blue nanozymes in AHPRzyme have catalase (CAT) activity, which decomposes H<sub>2</sub>O<sub>2</sub> in human nasopharyngeal carcinoma CEN2 cells into non-toxic H<sub>2</sub>O, reducing H<sub>2</sub>O<sub>2</sub> levels and minimizing damage to normal cells. The released O<sub>2</sub> helps alleviate the hypoxic environment of the tumor, inhibiting lactate production due to hypoxia and consequently suppressing tumor growth. ② The prussian blue nanozymes also have peroxidase (POD) activity, which catalyzes H<sub>2</sub>O<sub>2</sub> in tumor cells to generate ·OH, a reactive oxygen species, leading to tumor cell apoptosis. ③ The α-lipoic acid structure in AHPRzyme contains disulfide bonds that react with GSH, depleting excess glutathione (GSH) in tumor cells, disrupting the oxidative stress balance within the cells, and making them more sensitive to reactive oxygen species, thereby increasing tumor cell apoptosis. In summary, AHPRzyme can inhibit tumor cell growth and promote tumor cell apoptosis by improving the tumor microenvironment, achieving the goal of anti-nasopharyngeal carcinoma therapy.</p>","PeriodicalId":15138,"journal":{"name":"Journal of Biomaterials Applications","volume":" ","pages":"1177-1187"},"PeriodicalIF":2.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Degradation and transformation of tylvalosin by newly selected Providencia vermicola strain CT1: removal efficiency, pathways, mechanisms, and actual applications.
IF 3.5 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-05-01 Epub Date: 2025-03-12 DOI: 10.1007/s00449-025-03140-6
Ruina Chai, Meng Meng, Qi Li, Hansong Zhao, Yinglin Zhao, Jianxiang Zhong, Yunying Liu, Wenyuan Zhao, Xiaoxia Wang, Jianguo Cheng

Tylvalosin (TAT) is a widely used veterinary antibiotic whose residual contaminants promote antibiotic resistance and pose potential risks to human health and ecosystems. This study successfully isolated and identified a TAT-degrading bacterial strain, Providencia vermicola strain CT1, through 16S rRNA analysis and biochemical tests. Under optimized conditions (30 °C, pH = 6, initial TAT concentration of 300 mg/L, and bacterial culture volume of 50 mL), strain CT1 achieved a TAT degradation percentage of 97.1%. The degradation process followed a first-order kinetic model and was primarily driven by extracellular metabolites. GC-MS analysis identified that strain CT1 degrades TAT to produce small molecules such as 3-methylbutanoic acid, ethyl acetate, and 3-iminopentan-2-one. Strain CT1 effectively degraded TAT in actual wastewater samples, achieving 95% degradation within 60 h, and significantly reduced the COD, BOD₅, and NH₄⁺-N concentrations. These findings provide theoretical guidelines for removing TAT and other macrolide antibiotic contaminants from the environment.

{"title":"Degradation and transformation of tylvalosin by newly selected Providencia vermicola strain CT1: removal efficiency, pathways, mechanisms, and actual applications.","authors":"Ruina Chai, Meng Meng, Qi Li, Hansong Zhao, Yinglin Zhao, Jianxiang Zhong, Yunying Liu, Wenyuan Zhao, Xiaoxia Wang, Jianguo Cheng","doi":"10.1007/s00449-025-03140-6","DOIUrl":"10.1007/s00449-025-03140-6","url":null,"abstract":"<p><p>Tylvalosin (TAT) is a widely used veterinary antibiotic whose residual contaminants promote antibiotic resistance and pose potential risks to human health and ecosystems. This study successfully isolated and identified a TAT-degrading bacterial strain, Providencia vermicola strain CT1, through 16S rRNA analysis and biochemical tests. Under optimized conditions (30 °C, pH = 6, initial TAT concentration of 300 mg/L, and bacterial culture volume of 50 mL), strain CT1 achieved a TAT degradation percentage of 97.1%. The degradation process followed a first-order kinetic model and was primarily driven by extracellular metabolites. GC-MS analysis identified that strain CT1 degrades TAT to produce small molecules such as 3-methylbutanoic acid, ethyl acetate, and 3-iminopentan-2-one. Strain CT1 effectively degraded TAT in actual wastewater samples, achieving 95% degradation within 60 h, and significantly reduced the COD, BOD₅, and NH₄⁺-N concentrations. These findings provide theoretical guidelines for removing TAT and other macrolide antibiotic contaminants from the environment.</p>","PeriodicalId":9024,"journal":{"name":"Bioprocess and Biosystems Engineering","volume":" ","pages":"749-760"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhancement of natamycin production by combining ARTP mutagenesis with temperature control strategy development in Streptomyces gilvosporeus.
IF 3.5 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-05-01 Epub Date: 2025-03-18 DOI: 10.1007/s00449-025-03145-1
Jian Xue, Wen Xiao, Yuxiu Xu, Liang Wang, Jianhua Zhang, Hongjian Zhang, Xusheng Chen

Natamycin, a natural antifungal compound produced by Streptomyces, possesses antibacterial activity against yeast and mold. However, its low yield hinders widespread application in the food and pharmaceutical industries. This study aims to enhance natamycin production of Streptomyces gilvosporeus through engineering strain and optimization bioprocess. A high-yield strain exhibiting robust genetic stability was bred, yielding a 19.8% increase in shake flask fermentation and a 26.3% increase in fed-batch fermentation compared to the starting strain. The influence of temperature on high-yield strains was examined separately through batch fermentation and fed-batch fermentation. Subsequently, based on comprehensive analysis of fermentation kinetic parameters, a two-stage temperature control strategy was proposed. Specifically, the temperature was maintained at 30 ℃ for the first 18 h to shorten the lag phase, followed by a reduction to 26 ℃ and maintaining this temperature until the end of fermentation. Under this strategy, the natamycin production reached 14.4 g·L-1, representing a 25.2% increase compared to constant temperature fermentation at 28 ℃. This study provided an efficient production strategy for natamycin.

{"title":"Enhancement of natamycin production by combining ARTP mutagenesis with temperature control strategy development in Streptomyces gilvosporeus.","authors":"Jian Xue, Wen Xiao, Yuxiu Xu, Liang Wang, Jianhua Zhang, Hongjian Zhang, Xusheng Chen","doi":"10.1007/s00449-025-03145-1","DOIUrl":"10.1007/s00449-025-03145-1","url":null,"abstract":"<p><p>Natamycin, a natural antifungal compound produced by Streptomyces, possesses antibacterial activity against yeast and mold. However, its low yield hinders widespread application in the food and pharmaceutical industries. This study aims to enhance natamycin production of Streptomyces gilvosporeus through engineering strain and optimization bioprocess. A high-yield strain exhibiting robust genetic stability was bred, yielding a 19.8% increase in shake flask fermentation and a 26.3% increase in fed-batch fermentation compared to the starting strain. The influence of temperature on high-yield strains was examined separately through batch fermentation and fed-batch fermentation. Subsequently, based on comprehensive analysis of fermentation kinetic parameters, a two-stage temperature control strategy was proposed. Specifically, the temperature was maintained at 30 ℃ for the first 18 h to shorten the lag phase, followed by a reduction to 26 ℃ and maintaining this temperature until the end of fermentation. Under this strategy, the natamycin production reached 14.4 g·L<sup>-1</sup>, representing a 25.2% increase compared to constant temperature fermentation at 28 ℃. This study provided an efficient production strategy for natamycin.</p>","PeriodicalId":9024,"journal":{"name":"Bioprocess and Biosystems Engineering","volume":" ","pages":"817-827"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
全部 ACS BIOMATER-SCI ENG ENERG FUEL IND ENG CHEM RES Biomater. Sci. Lab Chip Mol. Syst. Des. Eng. Adv. Healthcare Mater. AlChE J. Biotechnol. J. Comput.-Aided Civ. Infrastruct. Eng. J. Tissue Eng. Regener. Med. Microb. Biotechnol. Plant Biotechnol. J. Sol. RRL Acta Biomater. Appl. Energy BIOMASS BIOENERG Biomaterials Bioresour. Technol. Cem. Concr. Res. Chem. Eng. J.(CEJ) Chem. Eng. Sci. Combust. Flame Compos. Struct. COMPUT CHEM ENG Comput. Fluids Constr. Build. Mater. Curr. Opin. Chem. Eng. Dent. Mater. Desalination Electrochem. Commun. Fuel Fuel Process. Technol. Int. Commun. Heat Mass Transfer Int. J. Greenhouse Gas Control Int. J. Heat Fluid Flow Int. J. Heat Mass Transfer Int. J. Hydrogen Energy Int. J. Multiphase Flow Int. J. Therm. Sci. J. CO2 Util. J. Ind. Eng. Chem. J. Membr. Sci. J. Nat. Gas Sci. Eng. J. Nucl. Mater. J. Power Sources J. Mech. Behav. Biomed. Mater. J. Taiwan Inst. Chem. Eng. MAT SCI ENG A-STRUCT Mater. Sci. Eng. R Rep. Org. Electron. Powder Technol. Proc. Combust. Inst. Prog. Energy Combust. Sci. Prog. Surf. Sci. Remote Sens. Environ. Renewable Energy Sep. Purif. Technol. Sol. Energy IEEE Electr. Insul. Mag. IEEE J. Photovoltaics IEEE Trans. Device Mater. Reliab. IEEE Trans. Nanotechnol. IEEE Trans. Semicond. Manuf. IEEE Trans. Sustainable Energy Accredit. Qual. Assur. Acta Mech. Adsorption Appl. Biochem. Biotechnol. Appl. Nanosci. ARCH APPL MECH At. Energy Biodegradation Bioenergy Res. Biomass Convers. Biorefin. Biomech. Model. Mechanobiol. Biomed. Microdevices Biotechnol. Biofuels BMC Chem. Eng. Bull. Eng. Geol. Environ. Comput. Part. Mech. Continuum Mech. Thermodyn. Energy Effic. ENERGY SUSTAIN SOC Exp. Mech. Exp. Tech. Exp. Fluids Fire Technol. FLOW TURBUL COMBUST Fluid Dyn. FRONT ENERGY Front. Chem. Sci. Eng. Gold Bull. Granular Matter Instrum. Exp. Tech. Int. J. Fract. Int. J. Steel Struct. Int. J. Thermophys. J. Appl. Mech. Tech. Phys. J. Comput. Electron.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1