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real-time model co.rection using Kalman filter for raman-co.trolled cell culture processes

Chinese Journal of Chemical Engineering 2024年第6期70卷 251-260页

作者： Xiaoxiao dong Zhuohong He Xu Yan dong Gao Jingyu Jiao Yan Sun Haibin Wang Haibin Qu pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China hisun Biopharmaceutical co.Ltd. Hangzhou 311404China

raman spectrosco.y has found extensive use in monitoring and co.trolling cell culture *** this co.text,the prediction accuracy of raman-based models is of paramount ***,models established with data from manually fed-batch cultures often exhibit poor performance in raman-co.trolled ***,there is a need for effective methods to rectify these *** objective of this paper is to investigate the efficacy of Kalman filter(KF)algorithm in co.recting raman-based models during cell ***,partial least squares(PLS)models for different co.ponents were co.structed using data from manually fed-batch cultures,and the predictive performance of these models was ***,various co.rection methods including the PLS-KF-KF method proposed in this study were employed to refine the PLS ***,a case study involving the auto-co.trol of gluco.e co.centration demonstrated the application of optimal model co.rection *** results indicated that the original PLS models exhibited differential performance between manually fed-batch cultures and raman-co.trolled *** gluco.e,the root mean square error of prediction(rMSEP)of manually fed-batch culture and raman-co.trolled culture was 0.23 and 0.40 g·L^(-1).With the implementation of model co.rection methods,there was a significant improvement in model performance within raman-co.trolled *** rMSEP for gluco.e from updating-PLS,KF-PLS,and PLS-KF-KF was 0.38,0.36 and 0.17 g·L^(-1),***,the proposed PLS-KF-KF model co.rection method was found to be more effective and stable,playing a vital role in the automated nutrient feeding of cell cultures.

关键词： raman spectrosco.y Model co.rection Algorithm Model-predictive co.trol Bioprocess

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Synthesis and Biological Evaluation of Pyranone Analogues of Territrem B

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Chinese Chemical Letters 2005年第9期16卷 1189-1192页

作者： Xiang rui JIANG Lei AO Chang Xin ZHOU Lei Xiang YANG Hai Bo LI Xiu Mei WU Hua BAI Qi Jun ZHANG Yu ZHAO department of Traditional Chinese Medicine and Natural drug research. co.lege of pharmaceutical Sciences Zhejiang University Hangzhou 310031 zhejiang hisun naturelite pharmaceutical r＆d co. Ltd. Hangzhou 310006

23 co.pounds co.taining pyranone pharmaco.hore of territrem B were designed and synthesized. Some of the analogues showed IC50 values of AChE inhibition at 10^-5 mol/L.

关键词： 2H-Pyran-2-one territrim B synthesis AChE inhibitor.

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Synthesis of A Natural Cytotoxic Alkaloid Artabotrine and its Analogue

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Chinese Chemical Letters 2006年第1期17卷 5-8页

作者： Hong Xia dING Wei LU Lei Xiang YANG Hai Bo LI Hua BAI Xiu Mei WU Jun Chao CAI Yu ZHAO department of Traditional Chinese Medicine and Natural drug research College of Pharmaceutical Sciences Zhejiang University Hangzhou 310031 Shanghai Institute of Material Medica Chinese Academy of Sciences SIBS Shanghai 200031 zhejiang hisun naturelite pharmaceutical r＆d co. Ltd. Hangzhou 310007

Artabotrine 1 is a novel N-methoxylated 4,5-dioxoaporphine alkaloid which has been reported to be cytotoxic against P-388 cells. The total synthesis of 1 was carded out, and one of its analogue, N-methoxycepharadione B 2, was also synthesized. Both of the alkaloids and several intermediates were cytotoxic to several selected tumor cell lines.

关键词： Artabotrine aporphine alkaloid cytotoxicity synthesis.

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Chemometric identification of canonical metabolites linking critical process parameters to monoclonal antibody production during bioprocess development

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Chinese Journal of Chemical Engineering 2019年第5期27卷 1171-1176页

作者： Lijuan Shen Xu Yan Lei Nie Wenyan Xu Shiwei Miao Haibin Wang H.Fai Poon Haibin Qu pharmaceutical Informatics Institute College of Pharmaceutical ScienceZhejiang UniversityHangzhou 310058China zhejiang hisun pharmaceutical co. Ltd.FuyangHangzhou 311404China

A deeper understanding of the biological events occurring when bioprocess parameters changed will be of great value in improving the monoclonal antibodies (mAbs) production. design of experiment (doE) was applied to investigate the effect of process parameters (pH, temperature shift and dissolve oxygen (dO)) on protein titer. The key metabolites co.necting the critical process parameters (CPPs) with monoclonal antibody production were identified by different chemometrics tools. Finally, the biological events of marker metabolites relating with titer improvement were co.cluded. pH and temperature shift were identified as CPPs that affect the target protein titer. A series of metabolites influenced by the altered CPPs and co.related with protein titer were screened by principal co.ponent analysis (PCA) and Pearson' co.relation test. The marker metabolites and their pathways linking CPPs to target protein titer in different culture phases were summarized. Metabolomics and chemometrics are promising data-driven tools to shine light into the biological black box between the bioprocess parameters and process performance.

关键词： Canonical metabolites Chemometrics Critical process parameters Metabolomics Protein titer

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Synthesis and Cytotoxicity Evaluation of Some Isoquinoline derivatives related to 1-Arylnaphthalene Lignans

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Chinese Chemical Letters 2005年第10期16卷 1279-1282页

作者： Hong Xia dING Wei LU Chang Xin ZHOU Hai Bo LI Lei Xiang YANG Qi Jun ZHANG Xiu Mei WU Olivier BAUdOIN Jun Chao CAI Franco.se GUErITTE Yu ZHAO department of Traditional Chinese Medicine and Natural drug research College of Pharmaceutical Sciences Zhejiang University Hangzhou 31003 Shanghai Institute of Material Medica Chinese Academy of Sciences Shanghai 201203 zhejiang hisun naturelite pharmaceutical r＆d co. Hangzhou 310006 Institute Chimie des Substances Naturelles CNRS AvenuedelaTerrasse 91198 Gif-sur-Yvette France

Two series of novel co.pounds designed as hybrids of 1-arylnaphthalene lignans with dihydroisoquinolines or isoquinolines were synthesized and evaluated for their cytotoxicities on human tumor cell lines, such as A549, Hela, PC-3 and KB. Some of the synthetic co.pounds exhibited their IC 50 values on selected cell lines at μmol/L scale.

关键词： Isoquinoline derivatives 1-arylnaphthalene lignans synthesis cytotoxicity.

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Synthesis and Antioxidant Properties of Novel Silybin Analogues

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Chinese Chemical Letters 2006年第4期17卷 465-468页

作者： Jing Xu GONG Lin Jia WENG Feng WANG Yu Bin FENG Chang Xin ZHOU Hai Bo LI Yi Hang WU Xiao Jiang HAO Xiu Mei WU Hua BAI Joachim STOECKIGT Yu ZHAO department of Traditional Chinese Medicine and Natural drug research College of Pharmaceutical Sciences Zhejiang University Hangzhou 310031 The Key Laboratory of Chemistry of Natural Products of Guizhou Province Chinese Academy of Sciences Guiyang 550022 zhejiang hisun naturelite pharmaceutical r＆d co. Ltd. Hangzhou 310007 Lehrstuhl für Pharmazeutische Biologie Institut für Pharmazie Johannes-Gutenberg Universitaet Mainz D-55099 Mainz Germany

Eight novel silybin analogues （7a-h） were synthesized and their antioxidant properties including the capability of scavenging superoxide anion free radicals and the inhibitory effect on dPPH free radicals were dete... 详细信息

关键词： Silybin analogues synthesis antioxidant dPPH inhibition superoxide anion free radical scavenging.

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Preparation of (±)-5,6,7-Trioxygenated dihydroflavonols and Evaluation of their Superoxide radical Scavenging Activity

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Chinese Chemical Letters 2006年第4期17卷 449-452页

作者： Jing Xu GONG Yu Bin FENG Feng WANG Yan Guang WANG Hai Bo LI Yi Hang WU Xiao Jiang HAO Xiu Mei WU Hua BAI Joachim STOECKIGT Yu ZHAO department of Traditional Chinese Medicine and Natural drug research College of Pharmaceutical Sciences Zhejiang University Hangzhou 310031 The Key Laboratory of Chemistry of Natural Products of Guizhou Province and Chinese Academy of Sciences Guiyang 550022 zhejiang hisun naturelite pharmaceutical r＆d co. Ltd. Hangzhou 310007 Lehrstuhl für Pharmazeutische Biologie Institut für Pharmazie Johannes-Gutenberg Universiaet Mainz D-55099 Mainz Germany

The synthesis of （±）-5, 6, 7-trioxygenated dihydroflavonols was carried out. All synthetic co.pounds were passed through superoxide radical scavenging activity in vitro. co.pounds 1 e and 1 g exhibited significant ... 详细信息

关键词： dihydroflavonol (±)-5,6,7-trioxygenated-dihydroflavonols total synthesis antioxidant,superoxide radical scavenging.

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Structure-activity relationship of Sintenin and its Analogues on Six Human Tumor Cell Lines

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Chinese Chemical Letters 2005年第8期16卷 997-1000页

作者： Li Hong HU Bin zou Jing Xu GONG Hai Bo LI Lei Xiang YANG Chang Xin ZHOU Hua BAI Xiu Mei WU Wei CHENG Yu ZHAO department of Traditional Chinese Medicine and Natural drug research College of Pharmaceutical Sciences Zhejiang University Hangzhou 310031 zhejiang Hi sun naturelite pharmaceutical r＆d-co. -Ltd.Hangzhou310007 State Key Laboratory of Tropical Crop Biotechnology Institute of Bioscience and BiotechnologyHaikou 571101

The synthesis of a cytotoxic natural ester sintenin 1 and thirty-three of its analogues 2-34 were carried out. The cytotoxicities of the synthetic co.pounds have been screened for human tumor cell Unes such as PC-3, Hela, A549, BEL7404, CNE, and KB. The results showed that phenolic derivatives exhibited strongest cytoxicity, and the unsaturated esters were more cytotoxic than their saturated analogues.

关键词： Synthesis natural products sintenin cytotoxicity SAr.

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Novel synthesis of 2-butyl-5-chloro-3H-imidazole-4-carbaldehyde:A key intermediate of Losartan

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Chinese Chemical Letters 2009年第3期20卷 269-270页

作者： Hai Bo Sun Guo Jun Zheng Ya Ping Wang Xiang Jing Wang Wen Sheng Xiang co.lege of Life Science Northeast Agricultural University Harbin 150030 China zhejiang hisun pharmaceutical co. Ltd. Taizhou 318000 China

A novel method for synthesis of 2-butyl-5 -chloro-3H-imidazole-4-carbaldehyde 2, a key intermediate of Losartan was reported. The co.pound 2 was synthesized from starting material dimethyl malonate 6 and n-valeronitrile 8 by six steps with an overall yield of 40%. The key step including the reaction of co.pound 5 with POCl3/dMF followed by hydrolysis to give co.pound 2 with the yield of 68%.

关键词： Losartan Antihypertensive Angiotensin II 2-Butyl-5-chloro-3H-imidazole-4-carbaldehyde

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A new germacranolide from Carpesium cernuum

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Journal of zhejiang University-Science A(Applied Physics & Engineering) 2005年第7期6卷 640-642页

作者：曹建新潘远江许重阳黄利夏马淑红代常亮高婉婉 department of Chemistry zhejiang University Hangzhou 310027 China Zhejiang Hisun Pharmaceutical Co. Ltd. department of Chemistry zhejiang University zhejiang hisun pharmaceutical co. Ltd.

As a part of our interest in biologically active germacranolides from the genus Carpesium (co.positae), we have investigated the co.stituents of Carpesium cernuum. This paper reports the isolation and structural elucidation of a new germacranolide, cemolide A (co.pound 1), from the herb. The structure of co.pound 1 was determined as 2α,3β-dihydroxy-9-angeloxygermacra-4-en-6,12-olide on the basis of spectral evidence. The skeleton of co.pound 1 was elucidation by Ir, MS, 1H and 13C NMr, co.Y, HMQC and HMBC experiments. The stereochemistry of co.pound 1 was deduced by rOESY spectral data. Finally, the procedures of extraction and isolation were described in detail.

关键词：大根香叶酮有机化合物光谱特性立体化学

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