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Mimotope peptide modified pompon mum-like magnetic microparticles for precise recognition,capture and biotransformation analysis of rituximab in biological fluids

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1317-1328页

作者： Jiawen Yang Aixuan zhou Minyi Li Qiaoxian He jingwei zhou Jacques Crommen Wentao Wang Zhengjin Jiang Qiqin Wang Institute of Pharmaceutical Analysis College of Pharmacy/State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education(MOE)of ChinaJinan UniversityGuangzhou 510632China Laboratory for the Analysis of Medicines Department of Pharmaceutical SciencesCIRMUniversity of LiegeLiege B-4000Belgium SCIEX Shanghai 200050China

Due to low immobilized ligand density,limited binding capacity,and severe interference from serum proteins,developing ideal peptide-based biomaterials for precise recognition and in vivo analysis of biopharmaceuticals remains a huge challenge.In this study,mimotope peptide modified pompon mum-like biomimetic magnetic microparticles(MMPs,3.8μm)that mimic the specific functionalities of CD20 on malignant B cells were developed for the first time.Benefit from the numerous ligand binding sites(Ni^(2+))on the pompon mum-like MMPs,these novel materials achieved≥10 times higher peptide ligand densities(>2300 mg/g)and antibody binding capacities(1380 mg/g)compared to previous reported biomaterials.Leveraging the high specificity of the mimotope peptide,rituximab can be precisely recognized and enriched from cell culture media or serum samples.We also established an LC-MS/MS method using the MMPs for tracking rituximab biotransformation in patient serum.Intriguingly,deamidation of Asn55 and Asn33,as well as oxidation of Met81 and Met34 were observed at the key complementarity determining regions of rituximab,which could potentially influence antibody function and require careful monitoring.Overall,these versatile biomimetic MMPs demonstrate superior recognition and enrichment capabilities for target antibodies,offering interesting possibilities for biotransformation analysis of biopharmaceuticals in patient serum.

关键词： Therapeutic monoclonal antibody Mimotope peptide Precise recognition Peptide-based biomaterials Biotransformation Patient serum

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Drug repurposing screening and mechanism analysis based on human colorectal cancer organoids

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Protein & Cell 2024年第4期15卷 285-304页

作者： Yunuo Mao Wei Wang jingwei Yang Xin zhou Yongqu Lu Junpeng Gao Xiao Wang Lu Wen Wei Fu Fuchou Tang School of Life Sciences Biomedical Pioneering Innovation CenterDepartment of General SurgeryThird HospitalPeking UniversityBeijing 100871China Beijing Advanced Innovation Center for Genomics(ICG) Ministry of Education Key Laboratory of Cell Proliferation and DifferentiationBeijing 100871China Peking-Tsinghua Center for Life Sciences Peking UniversityBeijing 100871China Peking University Third Hospital Cancer Center Beijing 100871China The Research Center of Stem Cell and Regenerative Medicine School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China

Colorectal cancer(CRC)is a highly heterogeneous cancer and exploring novel therapeutic options is a pressing issue that needs to be addressed.Here,we established human CRC tumor-derived organoids that well represent both morphological and molecular heterogeneities of original tumors.To efficiently identify repurposed drugs for CRC,we developed a robust organoid-based drug screening system.By combining the repurposed drug library and computation-based drug prediction,335 drugs were tested and 34 drugs with anti-CRC effects were identified.More importantly,we conducted a detailed transcriptome analysis of drug responses and divided the drug response signatures into five representative patterns:differentiation induction,growth inhibition,metabolism inhibition,immune response promotion,and cell cycle inhibition.The anticancer activities of drug candidates were further validated in the established patient-derived organoids-based xenograft(PDOX)system in vivo.We found that fedratinib,trametinib,and bortezomib exhibited effective anticancer effects.Furthermore,the concordance and discordance of drug response signatures between organoids in vitro and pairwise PDOX in vivo were evaluated.Our study offers an innovative approach for drug discovery,and the representative transcriptome features of drug responses provide valuable resources for developing novel clinical treatments for CRC.

关键词： colorectal cancer organoids drug repurposing patient-derived organoids-based xenograft mechanism of action

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Optimizing diabetic kidney disease animal models:Insights from a meta-analytic approach

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动物模型与实验医学(英文) 2023年第5期6卷 433-451页

作者： Fanghong Li Zhi Ma Yajie Cai jingwei zhou Runping Liu School of Chinese Materia Medica Beijing University of Chinese MedicineBeijingChina School of Life Sciences Beijing University of Chinese MedicineBeijingChina Department of Nephrology Dongzhimen HospitalThe First Affiliated Hospital of Beijing University of Chinese MedicineBeijingChina

Diabetic kidney disease(DKD)is a prevalent complication of diabetes,often leading to end-stage renal disease.Animal models have been widely used to study the pathogenesis of DKD and evaluate potential therapies.However,current animal models often fail to fully capture the pathological characteristics of renal injury observed in clinical patients with DKD.Additionally,modeling DKD is often a time-consuming,costly,and labor-intensive process.The current review aims to summarize modeling strategies in the establishment of DKD animal models by utilizing meta-analysis related methods and to aid in the optimization of these models for future research.A total of 1215 articles were retrieved with the keywords of“diabetic kidney disease”and“animal experiment”in the past 10 years.Following screening,84 articles were selected for inclusion in the meta-analysis.Review manager 5.4.1 was employed to analyze the changes in blood glucose,glycosylated hemoglobin,total cholesterol,triglyceride,serum creatinine,blood urea nitrogen,and urinary albumin excretion rate in each model.Renal lesions shown in different models that were not suitable to be included in the metaanalysis were also extensively discussed.The above analysis suggested that combining various stimuli or introducing additional renal injuries to current models would be a promising avenue to overcome existing challenges and limitations.In conclusion,our review article provides an in-depth analysis of the limitations in current DKD animal models and proposes strategies for improving the accuracy and reliability of these models that will inspire future research efforts in the DKD research field.

关键词： animal model diabetic kidney diseases meta-analysis

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On the Probability of Generating a Primitive Matrix

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Journal of Systems Science & Complexity 2024年第4期37卷 1755-1771页

作者： CHEN jingwei FENG Yong LIU Yang WU Wenyuan Chongqing Key Laboratory of Automated Reasoning and Cognition Chongqing Institute of Green and Intelligent Technology Chinese Academy of Sciences Chongqing College University of Chinese Academy of Sciences Key Laboratory of Advanced Manufacturing Technology of Ministry of Education Guizhou Universityy Information Science and Engineering Chongqing Jiaotong University

Given a k × n integer primitive matrix A（i.e., a matrix can be extended to an n × n unimodular matrix over the integers） with the maximal absolute value of entries ‖A‖ bounded by an integer λ from above, the authors study the probability that the m × n matrix extended from A by appending other m-k row vectors of dimension n with entries chosen randomly and independently from the uniform distribution over {0, 1, · · ·, λ-1} is still primitive. The authors present a complete and rigorous proof of a lower bound on the probability, which is at least a constant for fixed m in the range[k + 1, n-4]. As an application, the authors prove that there exists a fast Las Vegas algorithm that completes a k × n primitive matrix A to an n × n unimodular matrix within expected ?（nωlog ‖A‖） bit operations, where ? is big-O but without log factors, ω is the exponent on the arithmetic operations of matrix multiplication.

关键词： Integer matrix matrix completion probabilistic algorithm unimodular matrix

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AtVQ25 promotes salicylic acid-related leaf senescence by fine-tuning the self-repression of AtWRKY53

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Journal of Integrative Plant Biology 2024年第6期66卷 1126-1147页

作者： Qi Tan Mingming Zhao jingwei Gao Ke Li Mengwei Zhang Yunjia Li Zeting Liu Yujia Song Xiaoyue Lu Zhengge Zhu Rongcheng Lin Pengcheng Yin Chunjiang zhou Geng Wang Ministry of Education Key Laboratory of Molecular and Cellular Biology Hebei Research Center of the Basic Discipline of Cell BiologyHebei Collaboration Innovation Center for Cell Signaling and Environmental Adaptation Hebei Key Laboratory of Molecular and Cellular Biology College of Life Sciences Hebei Normal University College of Chemical Engineering Shijiazhuang University Institute of Botany Chinese Academy of Sciences

Most mechanistic details of chronologically ordered regulation of leaf senescence are unknown.Regulatory networks centered on AtWRKY53 are crucial for orchestrating and integrating various senescence-related signals. Notably, AtWRKY53binds to its own promoter and represses transcription of AtWRKY53, but the biological significance and mechanism underlying this selfrepression remain unclear. In this study, we identified the VQ motif-containing protein AtVQ25as a cooperator of AtWRKY53. The expression level of AtVQ25 peaked at mature stage and was specifically repressed after the onset of leaf senescence. AtVQ25-overexpressing plants and atvq25 mutants displayed precocious and delayed leaf senescence, respectively. Importantly, we identified AtWRKY53 as an interacting partner of AtVQ25. We determined that interaction between AtVQ25 and AtWRKY53 prevented AtWRKY53from binding to W-box elements on the AtWRKY53promoter and thus counteracted the selfrepression of AtWRKY53. In addition, our RNA-sequencing data revealed that the AtVQ25-AtWRKY53 module is related to the salicylic acid(SA) pathway. Precocious leaf senescence and SA-induced leaf senescence in AtVQ25-overexpressing lines were inhibited by an SA pathway mutant, atsid2, and Nah G transgenic plants; AtVQ25-overexpressing/atwrky53 plants were also insensitive to SA-induced leaf senescence. Collectively, we demonstrated that AtVQ25 directly attenuates the self-repression of AtWRKY53 during the onset of leaf senescence,which is substantially helpful for understanding the timing of leaf senescence onset modulated by AtWRKY53.

关键词： AtWRKY53 leaf senescence salicylic acid transcriptional regulation VQ motif-containing proteins

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Interface Engineering of Titanium Nitride Nanotube Composites for Excellent Microwave Absorption at Elevated Temperature

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Nano-Micro Letters 2024年第9期16卷 147-160页

作者： Cuiping Li Dan Li Shuai Zhang Long Ma Lei Zhang* jingwei Zhang Chunhong Gong College of Chemistry and Molecular Sciences Henan UniversityKaifeng 475004People’s Republic of China National and Local Joint Engineering Research Center for Applied Technology of Hybrid Nanomaterials Henan UniversityKaifeng 475004People’s Republic of China

Currently,the microwave absorbers usually suffer dreadful electromagnetic wave absorption(EMWA)performance damping at elevated temperature due to impedance mismatching induced by increased conduction loss.Consequently,the development of high-performance EMWA materials with good impedance matching and strong loss ability in wide temperature spectrum has emerged as a top priority.Herein,due to the high melting point,good electrical conductivity,excellent environmental stability,EM coupling effect,and abundant interfaces of titanium nitride(TiN)nanotubes,they were designed based on the controlling kinetic diffusion procedure and Ostwald ripening process.Benefiting from boosted heterogeneous interfaces between TiN nanotubes and polydimethylsiloxane(PDMS),enhanced polarization loss relaxations were created,which could not only improve the depletion efficiency of EMWA,but also contribute to the optimized impedance matching at elevated temperature.Therefore,the TiN nanotubes/PDMS composite showed excellent EMWA performances at varied temperature(298-573 K),while achieved an effective absorption bandwidth(EAB)value of 3.23 GHz and a minimum reflection loss(RLmin)value of−44.15 dB at 423 K.This study not only clarifies the relationship between dielectric loss capacity(conduction loss and polarization loss)and temperature,but also breaks new ground for EM absorbers in wide temperature spectrum based on interface engineering.

关键词： TiN nanotubes Interface engineering Polarization loss Impedance matching Electromagnetic wave absorption performance

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Flow excitation mechanisms of unbalanced impeller forces after pump power-trip of ultra-high head pump-turbines

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Science China(Technological Sciences) 2024年第5期67卷 1602-1611页

作者： FU XiaoLong LI DeYou LV jingwei YANG Biao WANG HongJie WEI XianZhu School of Energy Science and Engineering Harbin Institute of TechnologyHarbin150001China State Key Laboratory of Hydro-Power Equipment Harbin Institute of Large Electrical MachineryHarbin150040China

To elucidate the dynamic mechanisms of unbalanced impellers in ultra-high head pump-turbines(PTs),this study employed a one-and three-dimensional coupled method to simulate the pump power-trip(PPT)process of an ultra-high head PT.The investigation revealed two novel pulsation frequency components,denoted as fDVand fINFT,associated with impeller forces.The pulsation intensities of these components were markedly higher than those of rotor-stator interaction frequency components in ultra-high head PTs.Notably,the fDVcomponents exhibited pulsations at 1–2 times the rated rotation frequency of the impeller,spanning the entire transition period.Meanwhile,the fINFTcomponents constituted a complex frequency band with various frequency values,primarily occurring near conditions(Q=0,n=0,M=0,and d M/dt=0).These two pulsation frequency components were predominantly linked to the unsteady evolution of dean vortices inside the volute and complex transitions of the flow pattern within the impeller,respectively.It is crucial to note that these unbalanced flow-induced impeller axial forces can elevate the risk of accidents where the rotor is subjected to significant upwind axial forces.These findings offer valuable insights into mitigating the risk of rotor lifting due to axial forces during PT events in ultra-high head PTs.

关键词： ultra-high head pump-turbine pump power-trip unbalanced impeller forces pressure pulsations flow pattern transitions

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Deep Reinforcement Learning or Lyapunov Analysis?A Preliminary Comparative Study on Event-Triggered Optimal Control

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IEEE/CAA Journal of Automatica Sinica 2024年第7期11卷 1702-1704页

作者： jingwei Lu Lefei Li Qinglai Wei Fei-Yue Wang IEEE the Department of Industrial Engineering Tsinghua UniversityBeijing 100084China The State Key Laboratory for Management and Control of Complex Systems Institute of AutomationChinese Academy of SciencesBeijing 100190China

Dear Editor,This letter develops a novel method to implement event-triggered optimal control(ETOC) for discrete-time nonlinear systems using parallel control and deep reinforcement learning(DRL), referred to as Deep-ETOC. The developed Deep-ETOC method introduces the communication cost into the performance index through parallel control, so that the developed method enables control systems to learn ETOC policies directly without triggering conditions.

关键词： Deep letter enable

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Removal of pathogenic indicator microorganisms during partial nitrification:the role of free nitrous acid

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Frontiers of Environmental Science & Engineering 2024年第3期18卷 93-102页

作者： Jiaojiao Xu Xiaotian Chen Rui Tang jingwei Feng Shoujun Yuan Wei Wang Zhen-Hu Hu Anhui Engineering Laboratory of Rural Water Environment and Resource School of Civil EngineeringHefei University of TechnologyHefei 230009China Hefei 168 High School Hefei 230025China Shanghai Key Laboratory of Materials Protection and Advanced Materials in Electric Power Shanghai University of Electric PowerShanghai 200090China

Digested wastewater contains pathogenic microorganisms and high ammonia concentrations,which can pose a potential risk to public health.Effective removal of pathogens and nitrogen is crucial for the post-treatment of digested wastewater.Partial nitrification-anammox is an energy-saving nitrogen removal process.Free nitrous acid(FNA),an intermediate product of partial nitrification,has the potential to inactivate microorganisms.However,the efficiency and mechanisms of FNA-related inactivation in pathogens during partial nitrification remains unclear.In this study,Enterococcus and Escherichia coli(E.coli)were selected to investigate the efficiency and mechanisms of FNA-related inactivation in partial nitrification process.The results revealed that 83%±13%and 59%±27%of E.coli and Enterococcus were removed,respectively,in partial nitrification process at FNA concentrations of 0.023−0.028 mg/L.When the concentration of FNA increased from 0 to 0.5 mg/L,the inactivation efficiencies of E.coli and Enterococcus increased from 0 to 99.9%and 89.9%,respectively.Enterococcus exhibited a higher resistance to FNA attack compared to E.coli.3D-laser scanning microscopy(3D-LSM)and scanning electron microscopy(SEM)revealed that FNA exposure caused the surface collapse of E.coli and Enterococcus,as well as visible pore formation on the surface of E.coli cells.4',6-Diamidino-2-phenylindole dihydrochloride n-hydrate(DAPI)/propidium iodide(PI)and biomolecule leakage confirmed that inactivation of E.coli and Enterococcus occurred due to breakdown of cell walls and cell membranes.These findings indicate that partial nitrification process can be used for the removal of residual pathogenic microorganisms.

关键词： Partial nitrification Free nitrous acid Pathogenic indicator microorganism Inactivation Cell structure

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Rapid fabrication of zwitterionic sulfobetaine vinylimidazole-based monoliths via photoinitiated copolymerization for hydrophilic interaction chromatography

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Journal of Pharmaceutical Analysis 2022年第5期12卷 783-790页

作者： Qiqin Wang Lingjue Sun Huihui Wu Ning Deng Xianglong Zhao jingwei zhou Tingting Zhang Hai Han Zhengjin Jiang Institute of Pharmaceutical Analysis College of PharmacyJinan UniversityGuangzhou510632China Anhui Prevention and Treatment Center for Occupational Disease Anhui No.2 Provincial People's HospitalHefei230041China Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education Lab of BiochemistryCollege of ChemistryXiangtan UniversityXiangtanHunan411105China Department of Pharmacy and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine&New Drug Research Jinan UniversityGuangzhou510632China

Zwitterionic sulfobetaine-based monolithic stationary phases have attracted increasing attention for their use in hydrophilic interaction chromatography.In this study,a novel hydrophilic polymeric monolith was fabricated through photo-initiated copolymerization of 3-(3-vinyl-1-imidazolio)-1-propanesulfonate(SBVI)with pentaerythritol triacrylate using methanol and tetrahydrofuran as the porogenic system.Notably,the duration for the preparation of this novel monolith was as little as 5 min,which was significantly shorter than that required for previously reported sulfobetaine-based monoliths prepared via conventional thermally initiated copolymerization.Moreover,these monoliths showed good morphology,permeability,porosity(62.4%),mechanical strength(over 15 MPa),column efficiency(51,230 plates/m),and reproducibility(relative standard deviations for all analytes were lower than 4.6%).Mechanistic studies indicated that strong hydrophilic and negative electrostatic interactions might be responsible for the retention of polar analytes on the zwitterionic SBVI-based monolith.In particular,the resulting monolith exhibited good anti-protein adhesion ability and low nonspecific protein adsorption.These excellent features seem to favor its application in bioanalysis.Therefore,the novel zwitterionic sulfobetaine-based monolith was successfully employed for the highly selective separation of small bioactive compounds and the efficient enrichment of N-glycopeptides from complex samples.In this study,we prepared a novel zwitterionic sulfobetaine-based monolith with good performance and developed a simpler and faster method for preparation of zwitterionic monoliths.

关键词： Zwitterionic monolith Sulfobetaine Photo-initiated copolymerization Hydrophilic interaction chromatography Complex sample

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