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Ginsenoside Rk3 modulates gut microbiota and regulates immune response of group 3 innate lymphoid cells to against colorectal tumorigenesis

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Journal of Pharmaceutical Analysis 2024年第2期14卷 259-275页

作者： Xue Bai rongzhan fu Yannan Liu Jianjun Deng Qiang Fei Zhiguang Duan Chenhui Zhu Daidi Fan Shaanxi Key Laboratory of Degradable Biomedical Materials School of Chemical EngineeringNorthwest UniversityXi'an710069China Biotech&Biomed Research Institute Northwest UniversityXi'an710069China School of Chemical Engineering and Technology Xi'an Jiaotong UniversityXi'an710069China

The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer(CRC).However,the effect of ginsenoside Rk3(Rk3)on CRC and gut microbiota remains unclear.Therefore,the purpose of this study is to explore the potential effect of Rk3 on CRC from the perspective of gut microbiota and immune regulation.Our results reveal that treatment with Rk3 significantly suppresses the formation of colon tumors,repairs intestinal barrier damage,and regulates the gut microbiota imbalance caused by CRC,including enrichment of probiotics such as Akkermansia muciniphila and Barnesiella intestinihominis,and clearance of pathogenic Desulfovibrio.Subsequent metabolomics data demonstrate that Rk3 can modulate the metabolism of amino acids and bile acids,particularly by upregulating glutamine,which has the potential to regulate the immune response.furthermore,we elucidate the regulatory effects of Rk3 on chemokines and inflammatory factors associated with group 3 innate lymphoid cells(ILC3s)and T helper 17(Th17)signaling pathways,which inhibits the hyperactivation of the Janus kinase-signal transducer and activator of transcription 3(JAK-STAT3)signaling pathway.These results indicate that Rk3 modulates gut microbiota,regulates ILC3s immune response,and inhibits the JAK-STAT3 signaling pathway to suppress the development of colon tumors.More importantly,the results of fecal microbiota transplantation suggest that the inhibitory effect of Rk3 on colon tumors and its regulation of ILC3 immune responses are mediated by the gut microbiota.In summary,these findings emphasize that Rk3 can be utilized as a regulator of the gut microbiota for the prevention and treatment of CRC.

关键词： Colorectal cancer Ginsenoside Immune cells Gut microbiota

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Application and progress of techno-economic analysis and life cycle assessment in biomanufacturing of fuels and chemicals

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Green Chemical Engineering 2023年第2期4卷 189-198页

作者： rongzhan fu Lixia Kang Chenyue Zhang Qiang Fei Shaanxi Key Laboratory of Degradable Biomedical Materials School of Chemical EngineeringNorthwest UniversityXi'an710069China Shaanxi Key Laboratory of Energy Chemical Process Intensification School of Chemical Engineering and TechnologyXi'an Jiaotong UniversityXi'an710049China

To reduce the dependency on petroleum-based products and emission of greenhouse gas,renewable biofuels and chemicals play an important role to meet the unmatched energy demands of the rapidly growing population.However,most biofuel and chemical products do not reach the commercialization stage,mainly hindered by incomparable economics to petroproducts.Techno-economic assessment(TEA)is a useful tool to estimate eco-nomic performance,and identify bottlenecks for the development of biofuel and chemical production technology,meanwhile,life cycle assessment(LCA)is applied to assess sustainability by reducing the environmental impact of biofuel and chemical production.This present review covers TEA and LCA research progress in the manufacturing of biofuels and biochemical,and discusses the impacts of TEA and LCA results on the development and optimi-zation of biofuel and chemical production.In addition,challenges associated with TEA and LCA of biofuel and biochemical production were briefly overviewed,and potential approaches that may overcome such challenges were discussed enabling viable and sustainable biomanufacturing of fuels and chemicals.future integrated TEA and LCA studies could significantly promote the economic and sustainable development of the biomanufacturing process.

关键词： Techno-economic assessment Life cycle assessment Biomanufacturing fuels Chemicals Bioethanol Biodiesel

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Construction of multifunctional hydrogel based on the tannic acid-metal coating decorated MoS2 dual nanozyme for bacteria-infected wound healing

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Bioactive Materials 2022年第3期7卷 461-474页

作者： Yang Li rongzhan fu Zhiguang Duan Chenhui Zhu Daidi Fan Shaanxi Key Laboratory of Degradable Biomedical Materials School of Chemical EngineeringNorthwest UniversityXi’an710069ShaanxiChina Shaanxi R&D Center of Biomaterials and Fermentation Engineering School of Chemical EngineeringNorthwest UniversityXi’an710069ShaanxiChina Biotech.&Biomed.Research Institute Northwest UniversityXi’an710069ShaanxiChina

Bacterial infection,tissue hypoxia and inflammatory response can hinder the infected wound repair process.To mitigate the above issues,tannic acid-chelated Fe-decorated molybdenum disulfide nanosheets(MoS2@TA/Fe NSs)with dual enzyme activities were developed and anchored to a multifunctional hydrogel.The hydrogel exhibited excellent antibacterial ability owing to the combined effects of photothermal therapy(PTT),glutathione(GSH)loss,and the peroxidase(POD)-like activity(catalyse H2O_(2)into⋅OH under acid condition)of MoS2@TA/Fe NSs.Benefitting from the catalase(CAT)-like activity,the hydrogel could decompose H2O_(2)into O_(2)at neutral pH to relieve hypoxia and supply adequate O_(2).POD-like activity was mainly attributed to MoS2 NSs,while CAT-like activity was primarily due to TA/Fe complex.Moreover,MoS2@TA/Fe NSs endowed the hydrogel with outstanding anti-oxidant ability to scavenge redundant reactive oxygen species(ROS)and reactive nitrogen species(RNS)under neutral environment to maintain the balance of antioxidant systems and prevent inflammation.In addition,the hydrogel could inhibit the release of inflammatory factors for the anti-inflammatory property of TA.TA retained partial phenolic hydroxyl groups,which cross-linked the nanosheets to the network structure of the hydrogel and promoted the adhesion of hydrogels.Due to the dynamic boron ester bonds between polyvinyl alcohol(PVA),dextran(Dex),MoS2@TA/Fe,and borax,the hydrogel demonstrated fast self-healing and rapid shape adaptability.This shape-adaptable adhesive hydrogel could fill the whole wound and closely contact the wound,ensuring that it achieved its functions with maximum efficiency.The MoS2@TA/Fe nanozyme-anchored multifunctional hydrogel showed high potential for bacteria-infected wound healing.

关键词： MoS2@TA/Fe nanozyme Multifunctional hydrogel POD-Like CAT-Like Anti-inflammation

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Glucose and MMP-9 dual-responsive hydrogel with temperature sensitive self-adaptive shape and controlled drug release accelerates diabetic wound healing

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Bioactive Materials 2022年第11期7卷 1-17页

作者： Wanyi Zhou Zhiguang Duan Jing Zhao rongzhan fu Chenhui Zhu Daidi Fan Shaanxi Key Laboratory of Degradable Biomedical Materials School of Chemical EngineeringNorthwest UniversityXi’an710069ShaanxiChina Shaanxi R&D Center of Biomaterials and Fermentation Engineering School of Chemical EngineeringNorthwest UniversityXi’an710069ShaanxiChina Biotech.&Biomed.Research Institute Northwest UniversityXi’an710069ShaanxiChina

Chronic diabetic wounds are an important healthcare challenge. High concentration glucose, high level of matrix metalloproteinase-9 (MMP-9), and long-term inflammation constitute the special wound environment of diabetic wounds. Tissue necrosis aggravates the formation of irregular wounds. All the above factors hinder the healing of chronic diabetic wounds. To solve these issues, a glucose and MMP-9 dual-response temperature-sensitive shape self-adaptive hydrogel (CBP/GMs@Cel&INS) was designed and constructed with polyvinyl alcohol (PVA) and chitosan grafted with phenylboric acid (CS-BA) by encapsulating insulin (INS) and gelatin microspheres con-taining celecoxib (GMs@Cel). Temperature-sensitive self-adaptive CBP/GMs@Cel&INS provides a new way to balance the fluid-like mobility (self-adapt to deep wounds quickly, approximately 37 ◦C) and solid-like elasticity (protect wounds against external forces, approximately 25 ◦C) of self-adaptive hydrogels, while simultaneously releasing insulin and celecoxib on-demand in the environment of high-level glucose and MMP-9. Moreover, CBP/ GMs@Cel&INS exhibits remodeling and self-healing properties, enhanced adhesion strength (39.65 ± 6.58 kPa), down-regulates MMP-9, and promotes cell proliferation, migration, and glucose consumption. In diabetic full-thickness skin defect models, CBP/GMs@Cel&INS significantly alleviates inflammation and regulates the local high-level glucose and MMP-9 in the wounds, and promotes wound healing effectively through the synergistic effect of temperature-sensitive shape-adaptive character and the dual-responsive system.

关键词： Dual-responsive Temperature-sensitive Shape self-adaptive hydrogels Diabetic wound healing

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High efficiency production of ginsenoside compound K by catalyzing ginsenoside Rb1 using snailase

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Chinese Journal of Chemical Engineering 2018年第7期26卷 1591-1597页

作者： Zhiguang Duan Chenhui Zhu Jingjing Shi Daidi Fan Jianjun Deng rongzhan fu Rong Huang Cuiying Fan Shaanxi Key Laboratory of Degradable Biomedical Materials School of Chemical EngineeringNorthwest UniversityTaibai North Road 229Xi'an 710069China Shanxi R&D Center of Biomaterials and Fermentation Engineering School of Chemical Engineering Northwest University Taibai North Road 229Xi'an 710069China

The rare ginsenoside Compound K(C-K) is attracting more attention because of its good physiological activity and urgent need. There are many pathways to obtain ginsenoside C-K, including chemical and biological methods. Among these, the conversion of PPD-type ginsenosides by enzymatic hydrolysis is a trend due to its high efficiency and mild conditions. For effectively extracting from the other panaxadiol saponins, the conversion process for ginsenoside C-K was investigated using snailases in this study. The univariate experimental design and response surface methodology were used to determine the optimal hydrolysis conditions for the conversion of ginsenoside Rb1 into ginsenoside C-K by snailases. The optimum conditions were as follows: p H 5.12, temperature 51 °C, ratio of snailase/substrate 0.21, and reaction time 48 h. On the basis of these parameters, the addition of 1.0 mmol·L^(-1) ferric ion was found to significantly improve the enzymolysis of snailases for the first time. With the above conditions, the maximum conversion rate reached 89.7%, suggesting that the process can obviously increase the yield of ginsenoside C-K. The bioassay tests indicated that the ginsenoside C-K showed anti-tumor activity in a series of tumor cell lines. Based on these results, we can conclude that the process of rare ginsenoside CK production by enzymolysis with snailase is feasible, efficient, and suitable for the industrial production and application.

关键词：人参皂甙工业生产混合物催化水解作用反应时间生物鉴定温和条件

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Stability improvement of human collagenα1(I)chain using insulin as a fusion partner

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Chinese Journal of Chemical Engineering 2018年第12期26卷 2607-2614页

作者： Yu Mi Yuan Gao Daidi Fan Zhiguang Duan rongzhan fu Lihua Liang Wenjiao Xue Shanshan Wang Shaanxi R&D Center of Biomaterials and Fermentation Engineering School of Chemical Engineering Northwest UniversityXi'an 710069China Shaanxi Institute of Microbiology Xi'an 710043China School of Biological Science and Engineering Shaanxi University of Technology Hanzhong 723001China

To enhance the stability of recombinant human collagen α1(I) chains(rhCOL1 A1) in production and purification stages, a gene fragment fusing COL1 A1 and insulin protein coding domains was synthesized and inserted into the pPIC9 K expression vector. The fusion peptide-expressing Pichia pastoris strain was created by transformation.After optimization of shake flask cultures, the ultimate intracellular expression level of the insulin-collagen α1(I) chain fusion protein(INS-COL1 A1) reached about 300 mg·L^(-1), and no obvious protein degradation was found in the fermentation and purification processes. The His-tagged recombinant fusion protein was detected by western blotting and was effectively purified using Ni^(2+)-chelating chromatography. A prominent improvement in the stability of INS-COL1 A1 was observed compared to rhCOL1 A1 in vitro, and the rhCOL1 A1 released from the fusion protein was studied by LC–MS/MS and in bioassays. The results showed that the purified rhCOL1 A1 was consistent with the native protein in amino acid composition and had a similar biological compatibility. To our knowledge, this is the first study to demonstrate the use of insulin as a fusion protein to improve the stability of easily degradable proteins.

关键词： fusion expression Human collagen α1(I) chain Insulin Protein stability Pichia pastoris

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生地百合西洋参胶囊对小鼠睡眠的促进作用及其安全性研究

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中国兽医杂志 2024年第4期60卷 124-129页

作者：赵雨杰傅容湛郭佳琦朱晨辉西北大学化工学院西北大学生物医药研究院陕西西安710069 陕西省医疗器械质量检验院陕西咸阳712046

为了研究生地百合西洋参胶囊对小鼠睡眠的作用并对其毒理安全性进行评价,本试验以低[200 mg/(kg·bw)]、中[400 mg/(kg·bw)]、高[800 mg/(kg·bw)]剂量的生地百合西洋参胶囊连续给小鼠灌胃30 d,通过直接诱导睡眠试验、延长戊巴比妥钠... 详细信息

为了研究生地百合西洋参胶囊对小鼠睡眠的作用并对其毒理安全性进行评价,本试验以低[200 mg/(kg·bw)]、中[400 mg/(kg·bw)]、高[800 mg/(kg·bw)]剂量的生地百合西洋参胶囊连续给小鼠灌胃30 d,通过直接诱导睡眠试验、延长戊巴比妥钠睡眠时间试验、戊巴比妥钠阈下剂量催眠试验,以及小鼠脑组织中5羟色胺(5-HT)、γ-氨基丁酸(GABA)和多巴胺(DA)含量的检测,分析其改善睡眠的作用;以最大给药剂量试验(MTD)进行生地百合西洋参胶囊的小鼠急性毒性试验;以低[1 g/(kg·bw)]、中[2 g/(kg·bw)]、高[4 g/(kg·bw)]剂量的生地百合西洋参胶囊给大鼠连续灌胃30 d,评价其对大鼠的毒理安全性。结果显示,与对照组相比,生地百合西洋参胶囊对小鼠无直接诱导睡眠作用,不同剂量的生地百合西洋参胶囊均能显著延长小鼠的戊巴比妥钠睡眠时间(P0.05)。结果表明,生地百合西洋参胶囊具有改善小鼠睡眠的作用,其作用机制与对小鼠脑组织中5-HT、GABA和DA含量的调节有关,本试验所用剂量范围对大鼠和小鼠均无明显毒性,安全性良好。本试验结果可为生地百合西洋参胶囊的临床应用提供参考依据。

关键词：生地黄提取物百合提取物西洋参提取物胶囊改善睡眠安全性

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A Tutorial on Quantized Feedback Control

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IEEE/CAA Journal of Automatica Sinica 2024年第1期11卷 5-17页

作者： Minyue fu IEEE the School of System Design and Intelligent Manufacturing Shenzhen Key Laboratory of Control Theory and Intelligent Systems and Centre for Control Science and TechnologySouthern University of Science and TechnologyShenzhen 518055China

In this tutorial paper, we explore the field of quantized feedback control, which has gained significant attention due to the growing prevalence of networked control systems. These systems require the transmission of feedback information, such as measurements and control signals, over digital networks, presenting novel challenges in estimation and control design. Our examination encompasses various topics, including the minimal information needed for effective feedback control, the design of quantizers, strategies for quantized control design and estimation,achieving consensus control with quantized data, and the pursuit of high-precision tracking using quantized measurements.

关键词： Consensus control high-precision control networked control quantized estimation quantized feedback control robust control

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Coupling Coordination Analysis of Cropland Intensification and Agroecosystem Services:Evidence from Loess Plateau in Shaanxi Province,China

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Chinese Geographical Science 2024年第3期34卷 401-419页

作者： fu Shaowu fu Mengyu QIU Menglong Center for Land Resource Research in Northwest China Shaanxi Normal UniversityXi’an 710119China

One of the greatest challenges in the agroecosystem is to improve cropland intensification while preserving agroecosystem services.While many studies have investigated the effect of cropland intensification on agroecosystem service,the interactive coupling and coordination among these factors remain largely unexplored.In view of this,this study performed a case study of the Loess Plateau in Shaanxi Province,China and constructed comprehensive evaluation models to quantify the cropland intensification and agroecosystem service in this area.Balance analysis and the coupling coordination degree model were used to evaluate the interactive relationship between cropland intensification and agroecosystem service,and statistical analysis and spatial autocorrelation were used to analyze the spatial characteristics and potential mechanism of the coupling coordination.Results show that both the cropland intensification and agroecosystem service in the study area were relatively low yet gradually increased from 2000 to 2020.Agroecosystem service lag was identified as the dominant unbalanced development type.Improving the supply capacity of agroecosystem services plays a key role in the balanced development of cropland in the Loess Plateau.The coupling coordination degree between cropland intensification and agroecosystem service ranges from basic coordination to serious incoordination.Therefore,cropland intensification practices in the area should be optimized to enhance this coordination degree.An upward trend was also observed in the coupling coordination degree from2000 to 2020.The withdrawal of marginal cropland in the Grain for Green program is one of the most important reasons for this trend,especially for the northern region.Around 83.6%of the high-high clusters are concentrated in the southern region of the Loess Plateau,whereas 70.5%of the low-low clusters are distributed in the northern region.These clustering characteristics are mainly attributed to the environmental suitability of these areas for agriculture and

关键词： cropland intensification agroecosystem services balance analysis coupling coordination degree Loess Plateau,China

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A stochastic gradient-based two-step sparse identification algorithm for multivariate ARX systems

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Control Theory and Technology 2024年第2期22卷 213-221页

作者： Yanxin fu Wenxiao Zhao Key Laboratory of Systems and Control Academy of Mathematics and Systems ScienceChinese Academy of SciencesBeijing100190China School of Mathematical Sciences University of Chinese Academy of SciencesBeijing100049China

We consider the sparse identification of multivariate ARX systems, i.e., to recover the zero elements of the unknown parameter matrix. We propose a two-step algorithm, where in the first step the stochastic gradient (SG) algorithm is applied to obtain initial estimates of the unknown parameter matrix and in the second step an optimization criterion is introduced for the sparse identification of multivariate ARX systems. Under mild conditions, we prove that by minimizing the criterion function, the zero elements of the unknown parameter matrix can be recovered with a finite number of observations. The performance of the algorithm is testified through a simulation example.

关键词： ARX system Stochastic gradient algorithm Sparse identification Support recovery Parameter estimation Strong consistency

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