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Acta Pharmaceutica Sinica B 2024年第3期14卷 1400-1411页

作者： Shuo Wang Tian Liu Yuetong Huang Chaoying Du Danping Wang Xiyan Wang Qingzhi Lv Zhonggui He Yinglei Zhai Bingjun Sun Jin Sun Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China School of Medical Devices Shenyang Pharmaceutical UniversityShenyang 110016China School of Pharmacy Binzhou Medical UniversityBinzhou 256600China

The self-assembly prodrugs are usually consisted of drug modules,activation modules,and assembly *** the balance between efficacy and safety by selecting suitable modules remains a challenge for developing prodrug *** study designed four docetaxel(DTX)prodrugs using disulfide bonds as activation modules and different lengths of branched-chain fatty alcohols as assembly modules(C_(16),C_(18),C_(20),and C_(24)).The lengths of the assembly modules determined the self-assembly ability of prodrugs and affected the activation modules’*** extension of the carbon chains improved the prodrugs’self-assembly ability and pharmacokinetic behavior while reducing the cytotoxicity and increased cumulative *** use of C_(20) can balance efficacy and *** results provide a great reference for the rational design of prodrug nanoassemblies.

关键词： Prodrugs Nanoassemblies Self-assembly Branched-chain fatty alcohols Disulfide bond Docetaxel Efficacy Safety

Discovery of GluN2A subtype-selective N-methyl-d-aspartate(NMDA)receptor ligands

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Acta Pharmaceutica Sinica B 2024年第5期14卷 1987-2005页

作者： Liyang Jiang Na Liu Fabao Zhao Boshi Huang Dongwei Kang Peng Zhan Xinyong Liu department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China

The N-methyl-d-aspartate(NMDA)receptors,which belong to the ionotropic Glutamate receptors,constitute a family of ligand-gated ion *** the various subtypes of NMDA receptors,the GluN1/2A subtype plays a significant role in central nervous system(CNS)*** present article aims to provide a comprehensive review of ligands targeting GluN2A-containing NMDA receptors,encompassing negative allosteric modulators(NAMs),positive allosteric modulators(PAMs)and competitive ***,the ligands’structure–activity relationships(SARs)and the binding models of representative ligands are also discussed,providing valuable insights for the clinical rational design of effective drugs targeting CNS diseases.

关键词： NMDA receptors GluN2A subtype Subtype-selective ligands SARs Protein ligand interactions

An Improved Modulation Strategy for Single-phase Three-level Neutral-point-clamped Converter in Critical Conduction Mode

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Journal of Modern Power Systems and Clean Energy 2024年第3期12卷 981-990页

作者： Ning Li Yujie Cao Xiaokang Liu Yan Zhang Ruotong Wang Lin Jiang Xiao-Ping Zhang School of Electrical Engineering Xi’an University of TechnologyXi’anChina the department of Electronics Information and BioengineeringPolitecnico di MilanoMilanItaly Xi’an Jiaotong University Xi’anChina the department of Electrical Engineering and Electronics University of LiverpoolLiverpoolU.K. the department of Electronic Electrical and Systems EngineeringUniversity of BirminghamBirminghamU.K.

Two-level totem-pole power factor correction(PFC)converters in critical conduction mode(CRM)suffer from the wide regulation range of switching ***,in highfrequency applications,the number of switching times increases,resulting in significant switching *** solve these issues,this paper proposes an improved modulation strategy for the single-phase three-level neutral-point-clamped(NPC)converter in CRM with *** optimizing the discharging strategy and switching state sequence,the switching frequency and its variation range have been efficiently *** detailed performance analysis is also presented regarding the switching frequency,the average switching times,and the effect of voltage gain.A 2 k W prototype is built to verify the effectiveness of the proposed modulation strategy and analysis *** with the totem-pole PFC converter,the switching frequency regulation range of the three-level PFC converter is reduced by 36.48%and the average switching times is reduced by 45.10%.The experimental result also shows a 1.2%higher efficiency for the three-level PFC converter in the full load range.

关键词： Critical conduction mode(CRM) on-board charger switching frequency range switching times power factor correction(PFC) three-level converter

Vitrification cryopreservation of ligaments based on zwitterionic betaine

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Chinese Journal of Chemical Engineering 2024年第8期72卷 1-9页

作者： Liming Zhang Xinmeng Liu Haoyue Li Lei Zhang department of Biochemical Engineering Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering(MOE)School of Chemical Engineering and TechnologyTianjin UniversityTianjin 300350China Haihe Laboratory of Sustainable Chemical Transformations Tianjin 300192China

Ligament cryopreservation enables a prolonged shelf life of allogeneic ligament grafts,which is fundamentally important to ligament ***,conventional cryopreservation techniques fail to eliminate the damage caused by ice crystal growth and the toxicity of cryopreservation agents(CPAs).Here,we report a novel CPA vitrification formulation primarily composed of betaine for ligament *** optimization was conducted on the methods for vitrification and rewarming,as well as the loading and unloading conditions,based on the critical cooling rate(CCR),critical warming rate(CWR),and permeation properties of the *** biomechanical and histological level tests,we demonstrate the superior performance of our method in ligament *** 30 days of vitrification cryopreservation,parameters such as the Young's modulus,tensile stress,denaturation temperature,and glycosaminoglycans content of the ligament remained essentially *** work pioneers the application of ice-free cryopreservation for ligament and holds great potential for improving the long-term storage of ligament,providing valuable insights for future cryopreservation technique development.

关键词： Ligament Betaine Vitrification Cryopreservation

Advantages of nanocarriers for basic research in the field of traumatic brain injury

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Neural Regeneration Research 2024年第2期19卷 237-245页

作者： Xingshuang Song Yizhi Zhang Ziyan Tang Lina Du School of pharmaceutical Sciences Shandong University of Traditional Chinese MedicineJinanShandong ProvinceChina department of Pharmaceutics Beijing Institute of Radiation MedicineBeijingChina

A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain *** overcome this problem,researchers have begun to focus on nanocarriers and other brain-targeting drug delivery *** this review,we summarize the epidemiology,basic pathophysiology,current clinical treatment,the establishment of models,and the evaluation indicators that are commonly used for traumatic brain *** also report the current status of traumatic brain injury when treated with nanocarriers such as liposomes and *** can overcome a variety of key biological barriers,improve drug bioavailability,increase intracellular penetration and retention time,achieve drug enrichment,control drug release,and achieve brain-targeting drug ***,the application of nanocarriers remains in the basic research stage and has yet to be fully translated to the clinic.

关键词： blood-brain barriers brain targeting central nervous system extracellular vesicles inflammatory factor microglial cell nanocarriers nanoparticles neural restoration traumatic brain injury

Evaluation of sodium borocaptate(BSH)and boronophenylalanine(BPA)as boron delivery agents for neutron capture therapy(NCT)of cancer:an update and a guide for the future clinical evaluation of new boron delivery agents for NCT

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Cancer Communications 2024年第8期44卷 893-909页

作者： Rolf F.Barth Nilendu Gupta Shinji Kawabata department of Pathology The Ohio State UniversityColumbusOhioUSA department of Radiation Oncology The Ohio State UniversityColumbusOhioUSA department of Neurosurgery Osaka Medical and Pharmaceutical UniversityTakatsukiOsakaJapan

Boron neutron capture therapy(BNCT)is a cancer treatment modality based on the nuclear capture and fission reactions that occur when boron-10,a stable isotope,is irradiated with neutrons of the appropriate energy to produce boron-11 in an unstable form,which undergoes instantaneous nuclear fission to produce high-energy,tumoricidal alpha *** primary purpose of this review is to provide an update on the first drug used clinically,sodium borocaptate(BSH),by the Japanese neurosurgeon Hiroshi Hatanaka to treat patients with brain tumors and the second drug,boronophenylalanine(BPA),which first was used clinically by the Japanese dermatologist Yutaka Mishima to treat patients with cutaneous ***,BPA has become the primary drug used as a boron delivery agent to treat patients with several types of cancers,specifically brain tumors and recurrent tumors of the head and neck *** focus of this review will be on the initial studies that were carried out to define the pharmacokinetics and pharmacodynamics of BSH and BPA and their biodistribution in tumor and normal tissues following administration to patients with high-grade gliomas and their subsequent clinical use to treat patients with highgrade ***,wewill summarize the studies thatwere carried out in Japan with BSH and subsequently at our own institution,The Ohio State University,and those of several other ***,we will describe studies carried out in Japan with BPA and then in the United States that have led to its use as the primary drug that is being used clinically for ***,although there have been intense efforts to develop new and better boron delivery agents for BNCT,none of these have yet been evaluated *** present reportwill provide a guide to the future clinical evaluation of new boron delivery agents prior to their clinical use for BNCT.

关键词： Boron neutron capture therapy(BNCT) boronophenylalanine(BPA) brain tumors head and neck cancer sodium borocaptate(BSH)

Effect of magnetic resonance imaging in liver metastases

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World Journal of Gastroenterology 2024年第1期30卷 112-114页

作者： Xing-Liang Huang Xiao-Dong Wang Zhao-Miao Gong Yan-Feng Zheng Jing-Xin Mao department of Science and Education Dianjiang People's Hospital of ChongqingChongqing 408399China department of Science and Industry Chongqing Medical and Pharmaceutical CollegeChongqing 400030China

This letter to the editor is a commentary on a study titled"Liver metastases:The role of magnetic resonance imaging."Exploring a noninvasive imaging evaluation system for the biological behavior of hepatocellular carcinoma(HCC)is the key to achieving precise diagnosis and treatment and improving *** review summarizes the role of magnetic resonance imaging in the detection and evaluation of liver metastases,describes its main imaging features,and focuses on the added value of the latest imaging tools(such as T1 weighted in phase imaging,T1 weighted out of phase imaging;diffusion-weighted imaging,T2 weighted imaging).In this study,I investigated the necessity and benefits of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid for HCC diagnostic testing and prognostic evaluation.

关键词： Liver metastases Magnetic resonance imaging Liver-specific contrast agents Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid Hepatocellular carcinoma Hepatobiliary contrast agents

Dammarane-type triterpenoids from Gynostemma longipes and their protective activities on hypoxia-induced injury in PC12 cells

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Chinese Journal of Natural Medicines 2024年第5期22卷 466-480页

作者： LIANG Haizhen CHEN Xiaojuan LI Qi ZHANG Mengmeng LU Pengxin ZHANG Jie SONG Juan ZHANG Tao GUO Baolin MA Baiping department of pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China Institute of Medicinal Plant Development Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100193China AnKang Chia Tai pharmaceutical Co. Ltd.Shaanxi 725000China

Sixteen new dammarane-type triterpenoid saponins(1-16)featuring diverse structural variations in the side chain at C-17,along with twenty-one known analogues(17-37),have been isolated from the rhizomes of Gynostemma longipes ***,a plant renowned for its medicinal and edible *** structural elucidation of these compounds was accomplished through comprehensive analyses of 1D and 2D NMR and HRMS spectroscopic data,supplemented by comparison with previously reported *** assays on the isolates for their protective effects against hypoxia-induced damage in pheochromocytoma cells(PC12 cells)revealed that nine saponins exhibited significant anti-hypoxic *** investigation into the anti-hypoxia mechanisms of the representative saponins demonstrated that compounds 22 and 36 markedly reduced the levels of hypoxia-induced ***,these compounds were found to decrease the release of lactate dehydrogenase(LDH)and malondialdehyde(MDA),while increasing the activity of superoxide dismutase(SOD),thereby indicating that the saponins could mitigate hypoxia-induced injuries by ameliorating apoptosis and oxidative *** findings offer substantial evidence for the future utilization and development of ***,identifying dammarane-type triterpenoid saponins as its active anti-hypoxic constituents.

关键词： Gynostemma longipes Dammarane-type saponins Anti-hypoxia effect Apoptosis

Neurovascular unit on a chip:the relevance and maturity as an advanced in vitro model

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Neural Regeneration Research 2024年第6期19卷 1165-1166页

作者： Sujey Palma-Florez Anna Lagunas Mònica Mir Nanobioengineering Group Institute for Bioengineering of Catalonia(IBEC)Barcelona Institute of Science and Technology(BIST)BarcelonaSpain CIBER-BBN ISCIIIMadridSpain department of Electronics and Biomedical Engineering University of BarcelonaBarcelonaSpain

The brain is a high-energy demanding organ,consuming around 20%of the metabolic energy *** fulfill this demand,cerebral blood flow(CBF)supplies oxygen and glucose continuously through the intricate network of cerebral blood *** for many years brain activity and blood flow were conceived as independent processes,MRI-based functional brain imaging demonstrated that there is a coupling between them.

关键词： cerebral maturity consuming

A High-Affinity Methyl-CpG-Binding Protein for Endonuclease-Free and Label-Free DNA Methyltransferase Activity Detection

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Journal of Analysis and Testing 2024年第3期8卷 327-334页

作者： Yang Bai Shulin Tan Yingsong Sheng Yueqing Gu Haiping Wu Baicun Li Yunlong Liu department of Biomedical Engineering School of Engineering China Pharmaceutical University department of Clinical Pharmacy Jinling Hospital State Key Laboratory of Analytical Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine Medical School of Nanjing University School of pharmaceutical Sciences Southern Medical University National Center for Respiratory Medicine Center of Respiratory Medicine China-Japan Friendship Hospital

DNA methyltransferase(MTase) activity detection has received increasing attention as a promising biomarker and therapeutic target. However, most of these detection methods rely on endonuclease digestion and signal groups ***, we present a novel platform for sensing DNA MTase activity that overcomes these limitations. Our approach is both endonuclease-free and label-free, utilizing a combination of a high-affinity streptavidin-methyl-CpG-binding domain(SA-MBD) protein and surface plasmon resonance(SPR) technology. The SA-MBD protein specifically recognizes a hairpin probe containing methylated CpG sites, which is treated with *** MTase. This recognition event generates a corresponding SPR response signal. The limit of detection is as low as 0.016 U/mL, owing to the high-a ffinity of the SA-MBD ***, we have demonstrated the feasibility of our method for *** MTase activity analysis in serum and inhibitor screening, which implies the potential prospects for biomedical research.

关键词： Biosensing DNA methyltransferase Inhibitor screening Methyl-CpG-binding protein Surface plasmon resonance