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Real-time model correction using Kalman filter for Raman-controlled 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 spectroscopy has found extensive use in monitoring and controlling cell culture *** this context,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-controlled ***,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 correcting Raman-based models during cell ***,partial least squares(PLS)models for different components were constructed using data from manually fed-batch cultures,and the predictive performance of these models was ***,various correction methods including the PLS-KF-KF method proposed in this study were employed to refine the PLS ***,a case study involving the auto-control of glucose concentration demonstrated the application of optimal model correction *** results indicated that the original PLS models exhibited differential performance between manually fed-batch cultures and Raman-controlled *** glucose,the root mean square error of prediction(RMSEP)of manually fed-batch culture and Raman-controlled culture was 0.23 and 0.40 g·L^(-1).With the implementation of model correction methods,there was a significant improvement in model performance within Raman-controlled *** RMSEP for glucose 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 correction 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 spectroscopy Model correction Algorithm Model-predictive control Bioprocess

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Exogenous ketogenic supplements can mitigate the susceptibility to Alzheimer’s disease induced by chronic sleep deprivation:emerging role of Sirt1 in ferroptosis

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Food Science and Human Wellness 2024年

作者： Yueqi Yang Xueyan Wang Lu Chen Ning Zhang Shilei Ji Zhengping Wang Jun Han Yuming Wang Min Wen Pet Nutrition Rresearch and Development Center Gambol Pet Group co. Ltd. Institute of biopharmaceutical Research Liaocheng University college of Food Science and Engineering Ocean University of China

Emerging evidence supports that sleep disorders are the main risk factor for sporadic Alzheimer’s disease (AD)， and iron dysregulation may be the link between them. Our previous studies have confirmed that ketogenic diet (KD) can prevent chronic sleep deprivation-induced AD. However， it is uncertain whether exogenous ketones supplements (EKS)， as an alternative intervention， have the same effects as KD. Thus， we investigated the prophylactic efficiency of EKS on chronic sleep deprivation-induced AD and reveal the underlying mechanism focus on iron metabolism. We observed that the prophylactic efficacy of EKS against chronic sleep deprivation-induced AD was comparable to that of KD. Meanwhile， our results suggest that both EKS and KD inhibited iron metabolism disorder through regulation of iron metabolism-related proteins. Moreover， we found that both EKS and KD reduced hippocampal mitochondrial dysfunction and iron-mediated lipid peroxides. Furthermore， EX527 (Sirt1 inhibitor)， mostly abrogated these above protections of EKS， suggesting that the prophylactic effect of EKS on AD is partly dependent on Sirt1. Our findings provide novel evidence that EKS can be developed as functional foods to prevent or delay the development of AD， particularly in individuals with sleep disorders.

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Artificial Bear Bile:A Novel Approach to Balancing Medical Requirements and Animal Welfare

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Engineering 2024年第7期38卷 100-112页

作者： Yong Li Yuhong Huang Nan Feng Heping Zhang Jing Qu Shuanggang Ma Yunbao Liu Jiang Li Shaofeng Xu Ling Wang Mi Zhang Jie Cai Weiping Wang Ru Feng Hang Yu Bo Yu Dailiang Liang Heping Qin Suxiang Luo Yanfen Li Meifeng Li Ruihua Wang Chen Ma Yan Wang Xiaobo Cen Xiaoxian Xu Boli Zhang Xiaoliang Wang Shishan Yu State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine Tianjin 300250China Zhongshan Belling Biotechnology co. Ltd.Zhongshan 528437China Zhongshan Anshi biopharmaceutical co. Ltd.Zhongshan 528437China e WestChina-Frontier Pharma Tech Co.Ltd.Chengdu 610041China Tianjin University of Traditional Chinese Medicine Tianjin 301617China

Bear bile has been a valuable and effective medicinal material in traditional Chinese medicine(TCM)for over 13 ***,the current practice of obtaining it through bear farming is under scrutiny for its adverse impact on bear ***,we present a new approach for creating artificial bear bile(ABB)as a high-quality and sustainable alternative to natural bear *** study addresses the scientific challenges of creating bear bile alternatives through interdisciplinary collaborations across various fields,including resources,chemistry,biology,medicine,pharmacology,and TCM.A comprehensive efficacy assessment system that bridges the gap between TCM and modern medical terminology has been established,allowing for the systematic screening of therapeutic *** the utilization of chemical synthesis and enzyme engineering technologies,our research has achieved the environmentally friendly,large-scale production of bear bile therapeutic compounds,as well as the optimization and recomposition of ABB *** resulting ABB not only closely resembles natural bear bile in its composition but also offers advantages such as consistent product quality,availability of raw materials,and independence from threatened or wild *** preclinical efficacy evaluations have demonstrated the equivalence of the therapeutic effects from ABB and those from commercially available drained bear bile(DBB).Furthermore,preclinical toxicological assessment and phase I clinical trials show that the safety of ABB is on par with that of the currently used *** innovative strategy can serve as a new research paradigm for developing alternatives for other endangered TCMs,thereby strengthening the integrity and sustainability of TCM.

关键词： Artificial bear bile Chemical profile Formula optimization Pharmacodynamic consistency Preclinical toxicological assessment

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创制人工熊胆——在医药需求和动物福利之间实现平衡的创新路径（英文）

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Engineering 2024年第7期 100-112页

作者：李勇黄宇虹冯楠张和平屈晶马双刚刘云宝李江徐少锋王玲张咪蔡杰王伟平冯茹于航于博梁待亮秦和平罗素芗李艳芬李美凤王瑞华马辰王琰岑小波徐孝先张伯礼王晓良庾石山 State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine Zhongshan Belling Biotechnology co. Ltd. Zhongshan Anshi biopharmaceutical co. Ltd. WestChina-Frontier Pharma Tech co. Ltd. Tianjin University of Traditional Chinese Medicine

Bear bile has been a valuable and effective medicinal material in traditional Chinese medicine (TCM) for over 13 ***,the current practice of obtaining it through bear farming is under scrutiny for its adverse impact on bear ***,we present a new approach for creating artificial bear bile (ABB)as a high-quality and sustainable alternative to natural bear *** study addresses the scientific challenges of creating bear bile alternatives through interdisciplinary collaborations across various fields,including resources,chemistry,biology,medicine,pharmacology,and TCM.A comprehensive efficacy assessment system that bridges the gap between TCM and modern medical terminology has been established,allowing for the systematic screening of therapeutic *** the utilization of chemical synthesis and enzyme engineering technologies,our research has achieved the environmentally friendly,large-scale production of bear bile therapeutic compounds,as well as the optimization and recomposition of ABB *** resulting ABB not only closely resembles natural bear bile in its composition but also offers advantages such as consistent product quality,availability of raw materials,and independence from threatened or wild *** preclinical efficacy evaluations have demonstrated the equivalence of the therapeutic effects from ABB and those from commercially available drained bear bile (DBB).Furthermore,preclinical toxicological assessment and phase I clinical trials show that the safety of ABB is on par with that of the currently used *** innovative strategy can serve as a new research paradigm for developing alternatives for other endangered TCMs,thereby strengthening the integrity and sustainability of TCM.

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Boosting the Activity and Stability of the Photoreduction of Diluted co_(2) by copper Oxide Decorated CeO_(2) Hetero-shells

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Chemical Research in Chinese Universities 2024年第3期40卷 513-520页

作者： XIAO Mingjiao LI Di WEI Yanze HE Yilei WANG Zumin YU Ranbo Department of Physical Chemistry School of Metallurgical and Ecological EngineeringUniversity of Science&Technology BejingBeijing 100083P.R.China State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190P.R.China Key Laboratory of biopharmaceutical Preparation and Delivery Chinese Academy of SciencesBeijing 100190P.R.China

Inspired by the natural photosynthesis systems,the integrated harnessing and conversion of co_(2) present a promising solution for addressing the ever-rising global atmospheric concentration of co_(2).Hollow multi-shelled structured(HoMS)photocatalysts,featuring alternating shells and cavities,have recently gained recognition as efficient nano-reactors for capturing co_(2) molecules and facilitating effective photoreduction within these hierarchical structures,leveraging the preeminent enrichment *** this work,to augment the photocatalytic efficacy of HoMS in co_(2) treatment,highly dispersed Cu_(x)O nanoparticles(NPs)were incorporated on the CeO2 shells through a polymer-assisted impregnation method to create more active sites and strengthen the interaction between the hetero-shells and co_(2) *** photoreduction of the co_(2)-to-co rate under a diluted co_(2)(15%,volume fraction)atmosphere is improved by the introduction of Cu_(x)O NPs,with the highest co yielding rate reaching 120µmol·h^(−1)·g^(−1) without any sacrificial *** comparison experiments and theoretical calculations reveal that the Cu_(x)O NPs promote the adsorption of co_(2) molecules in HoMS,accelerate the charge transfer efficiency,and stabilize the surface oxygen vacancies(Ovs)during the photoreduction co_(2) conversion *** hope these easy-to-prepare HoMS nanoreactors can contribute to the effective enrichment and valorization of co_(2) in industrial exhaust gases.

关键词： Photoreduction co_(2) Cu_(x)O/CeO_(2)hollow multi-shell structure(HoMS) Hetero-shell

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Tailoring Classical conditioning Behavior in TiO_(2) Nanowires:ZnO QDs-Based Optoelectronic Memristors for Neuromorphic Hardware

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Nano-Micro Letters 2024年第7期16卷 265-280页

作者： Wenxiao Wang Yaqi Wang Feifei Yin Hongsen Niu Young-Kee Shin Yang Li Eun-Seong Kim Nam-Young Kim School of Information Science and Engineering University of JinanJinan 250022People’s Republic of China RFIC Centre NDAC CentreKwangwoon UniversityNowon-guSeoul 139-701South Korea Department of Electronics Engineering Kwangwoon UniversityNowon-GuSeoul 139-701South Korea School of Microelectronics Shandong UniversityJinan 250101People’s Republic of China Department of Molecular Medicine and biopharmaceutical Sciences Seoul National UniversitySeoul 08826South Korea

Neuromorphic hardware equipped with associative learn-ing capabilities presents fascinating applications in the next generation of artificial ***,research into synaptic devices exhibiting complex associative learning behaviors is still ***,an optoelec-tronic memristor based on Ag/TiO_(2) Nanowires:ZnO Quantum dots/FTO was proposed and constructed to emulate the biological associative learning *** implementation of synaptic behaviors,including long and short-term plasticity,and learning-forgetting-relearning behaviors,were achieved in the device through the application of light and electrical *** the optoelectronic co-modulated characteristics,a simulation of neuromorphic computing was conducted,resulting in a handwriting digit recognition accuracy of 88.9%.Furthermore,a 3×7 memristor array was constructed,confirming its application in artificial visual *** importantly,complex biological associative learning behaviors were emulated by mapping the light and electrical stimuli into conditioned and unconditioned stimuli,*** training through associative pairs,reflexes could be triggered solely using light ***-sively,under specific optoelectronic signal applications,the four features of classical conditioning,namely acquisition,extinction,recovery,and generalization,were elegantly *** work provides an optoelectronic memristor with associative behavior capabilities,offering a pathway for advancing brain-machine interfaces,autonomous robots,and machine self-learning in the future.

关键词： Artificial intelligence Classical conditioning Neuromorphic computing Artificial visual memory Optoelectronic memristors ZnO Quantum dots

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Enzyme-metal nanocomposites for antibacterial applications

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Particuology 2022年第5期20卷 134-139页

作者： Jiarong Xiong Xinyi cai Jun Ge Key Lab for Industrial Biocatalysis Ministry of EducationDepartment of Chemical EngineeringTsinghua UniversityBeijing 100084China Institute of biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate SchoolShenzhen 518055China

Metal nanoparticles have been used as antibacterial agents widely,and the combined use of enzymes and metal nanoparticles promotes antibacterial activity,achieving a synergistic ***,enzymes decrease the amounts of metals and increase biocompatibility,thereby reducing toxicity of ***,the efficiency of enzymes is hindered when coupled with metals,which causes deactivation in the function of *** can a balance be struck between metals and enzymes?Although the antibacterial mechanism of metal nanoparticles is relatively clear,how enzyme-metal nanocomposites work against bacteria is not ***,we describe several examples on the synthesis of enzyme-metal nanocomposites via co-immobilization or in situ reduction and summarize how enzyme-metal nanocomposites combat microorganisms.

关键词： Enzyme-metal nanocomposites Applications Preparations Antibacterial mechanisms

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Development of a fluorescent probe hydrolysis-insulated isothermal PCR for rapid and sensitive on-site detection of African swine fever virus

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Virologica Sinica 2022年第3期37卷 462-464页

作者： Tianli Zou Junhua Deng Xiangdong Li Shiyin Zhang Lingyan Chen Liying Hao Jinshan Zhuang Heng Wang Guihong Zhang Shengxiang Ge Kegong Tian Beijing Wantai biopharmaceutical co. LtdBeijing102206China Luoyang Putai Bio-Tech co.Ltd Luoyang471003China National Research Center for Veterinary Medicine Luoyang471003China School of Public Health Xiamen UniversityXiamen361102China ASFV Regional Reference Laboratory in Guangzhou South China Agricultural UniversityGuangzhou510642China

Dear Editor,African swine fever virus(ASFV),the sole member of the family Asfarviridae,is the causative agent of African swine fever(ASF),a viral disease that leads to high mortality in domestic *** firstly identified in Kenya in the 1920s,ASFV has been prevalent in Africa,Europe,and Russian Federation(Sanchez et al.,2019).Recently,ASFV was introduced to Asian countries including China,Mongolia,Vietnam,Cambodia,Laos and South Korea,which lead to huge economic losses to local pig industries(Li and Tian,2018;Gaudreault and Richt,2019).The first case of ASFV in China was reported in August 2018(Zhou et al.,2018).

关键词： swine hydrolysis African

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Current status and perspectives of regulatory T cell-based therapy

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Journal of Genetics and Genomics 2022年第7期49卷 599-611页

作者： Guojun Qu Jieqiong Chen Yangyang Li Yaqin Yuan Rui Liang Bin Li Shanghai Institute of Immunology Department of Immunology and MicrobiologyShanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghai 200025China Shanghai Affinity biopharmaceutical co. Ltd.781 Cailun RoadShanghai 201203China Unit of Immune and Metabolic Regulation School of Life Science and TechnologyShanghaiTech UniversityShanghai 201210China

The CD4FOXP3regulatory T(Treg)cells are essential for maintaining immune homeostasis in healthy *** from clinical trials of Treg cell-based therapies in patients with graft versus host disease(GVHD),type 1 diabetes(T1D),liver transplantation,and kidney transplantation have demonstrated that adoptive transfer of Treg cells is emerging as a promising strategy to promote immune *** we provide an overview of recent progresses and current challenges of Treg cell-based *** summarize the completed and ongoing clinical trials with human Treg ***,a few of the chimeric antigen receptor(CAR)-Treg cell therapies are currently undergoing clinical ***,we describe the new strategies for engineering Treg cells used in preclinical ***,we envision that the use of novel synthetic receptors,metabolic regulators,combined therapies,and in vivo generated antigen-specific or engineered Treg cells through the delivery of modified mRNA and CRISPR-based gene editing will further promote the advances of next-generation Treg cell therapies.

关键词： Regulatory T cell FOXP3 Chimeric antigen receptor Cell therapy CRISPR-Based gene editing mRNA-based therapy

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Effect and safety of anaprazole in the treatment of duodenal ulcers:a randomized,rabeprazole-controlled,phase Ⅲ non-inferiority study

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Chinese Medical Journal 2022年第24期135卷 2941-2949页

作者： Huiyun Zhu Xue Pan Li Zhang Hongxin Sun Huizhen Fan Zhongwei Pan Caibin Huang Zhenwang Shi Jin Ding Qi Wang Yiqi Du Nonghua Lyu Zhaoshen Li Department of Gastroenterology Changhai Hospital of Navy Military Medical UniversityShanghai 200433China Drug Clinical Trial Institution Changhai Hospital of Navy Military Medical UniversityShanghai 200433China Department of Gastroenterology Yichun People’s HospitalYichunJiangxi 336028China Department of Gastroenterology Meihekou Central HospitalMeihekouJilin 135099China Department of Gastroenterology The First Affiliated Hospital of Gannan Medical CollegeGanzhouJiangxi 341001China Department of Gastroenterology Hefei Second People’s HospitalHefeiAnhui 230011China Department of Gastroenterology Jinhua Central HospitalJinhuaZhejiang 321099China Department of Gastroenterology Anqing Municipal HospitalAnqingAnhui 246004China Department of Gastroenterology The First Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006China

Background:The pharmacokinetic and clinical behaviors of many proton pump inhibitors(PPIs)in peptic ulcer treatment are altered by CYP2C19 genetic *** non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with *** also explored the influence of Helicobacter pylori(***)infection status and CYP2C19 polymorphism on ***:In this multicenter,randomized,double-blind,double-dummy,positive-drug parallel-controlled,phase Ⅲ study,Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg+anaprazole placebo or rabeprazole placebo+anaprazole 20 mg once daily for 4 *** primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent *** endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 ***,exploratory subgroup analysis of the primary endpoint by *** status and CYP2C19 polymorphism was *** events were monitored for ***-inferiority analysis was conducted for the primary ***:The study enrolled 448 patients(anaprazole,n=225;rabeprazole,n=223).The 4-week healing rates were 90.9%and 93.7%for anaprazole and rabeprazole,respectively(difference,-2.8%[95%confidence interval,-7.7%,2.2%]),demonstrating non-inferiority of anaprazole to *** duodenal ulcer symptoms improved in 90.9%and 92.5%of patients,*** rates of individual symptoms were similar between the *** rates did not significantly differ by *** status or CYP2C19 genotype for either treatment *** incidence of treatment-emergent adverse events was similar for anaprazole(72/220,32.7%)and rabeprazole(84/219,38.4%).conclusions:The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ***:***,NCT04215653.

关键词： Cytochrome P-450 CYP2C19 Non-inferiority trial Peptic ulcer Polymorphism Genetic Proton pump inhibitors Anaprazole Rabeprazole

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