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Pharmaco-toxicological effects of the synthetic cannabinoids 4F-ABUTINACA, SDB-005, and JWH-018 in mice. In vitro and in vivo studies

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EUROPEAN JOURNAL OF PHARMACOLOGY 2025年 996卷 177586页

作者： Luo, xuwen Kuai, Lixin Shi, Xuesong Qiao, Yanling Li, Kaixi Xu, Deli Di, Bin Yan, Fang Xu, peng China Pharmaceut Univ Sch Pharm Nanjing 210009 Peoples R China China Pharmaceut Univ Joint Lab Key Technol Narcot Control Off China Natl Narcot Control Commiss Beijing 100193 Peoples R China Minist Publ Secur Drug Intelligence & Forens Ctr Key Lab Drug Monitoring & Control Beijing 100193 Peoples R China

Background: Synthetic cannabinoids (SCs) are currently one of the most severely abused new psychoactive substances in the world. However, there remains a notable lack of pharmacological data on the newly emerged synthetic cannabinoids. In the present study, the in vitro and in vivo pharmacological effects of the fourth-generation synthetic cannabinoids 4F-ABUTINACA and SDB-005 are determined and compared to those of the first-generation synthetic cannabinoid JWH-018. Methods: In this study, the affinities of three SCs for CB1 receptors were evaluated using surface plasmon resonance (SPR) experiments. The acute toxicity of these three SCs was assessed through the up-and-down procedure, while their cannabinoid-specific pharmacological effects were determined through tetrad assays, which examined parameters such as temperature regulation, analgesia, locomotor activity, and catalepsy. Additionally, conditioned place preference (CPP) experiments and a precipitated withdrawal tests were conducted to assess the psychoactive effects and physical dependence of the SCs. Results: SPR experiments and acute toxicity tests demonstrated that in vitro KD values were positively correlated with in vivo ED50 potency estimates. All SCs were found to induce the classical "tetrad effects" in a dose-dependent manner. Notably, all SCs displayed significant biphasic effects in CPP experiments. Following the administration of the CB1 receptor antagonist rimonabant, a significant increase in head twitches and paw tremors was observed, indicating that the physical dependence manifested after the ingestion of SCs is mediated by the CB1 receptor. Conclusions: These findings suggest that these SCs have cannabinoid-specific pharmacological effects and abuse potential, providing robust experimental data to support future regulatory efforts.

关键词： 4F-ABUTINACA SDB-005 JWH-018 Tetrad CPP Precipitated withdrawal

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Electrophysiological studies of transgenic long QT type 1 and type 2 rabbits reveal genotype-specific differences in ventricular refractoriness and His conduction

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AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 2010年第3期299卷 H643-H655页

作者： Odening, Katja E. Kirk, Malcolm Brunner, Michael Ziv, Ohad Lorvidhaya, Peem Liu, Gong Xin Schofield, Lorraine Chaves, Leonard peng, xuwen Zehender, Manfred Choi, Bum-Rak Koren, Gideon Brown Univ Warren Alpert Med Sch Rhode Isl Hosp Div CardiolCardiovasc Res Ctr Providence RI 02903 USA Univ Hosp Freiburg Freiburg Germany Penn State Univ Coll Med Dept Comparat Med Hershey PA USA

Odening KE, Kirk M, Brunner M, Ziv O, Lorvidhaya P, Liu GX, Schofield L, Chaves L, peng X, Zehender M, Choi B, Koren G. Electrophysiological studies of transgenic long QT type 1 and type 2 rabbits reveal genotype-specific differences in ventricular refractoriness and His conduction. Am J Physiol Heart Circ Physiol 299: H643-H655, 2010. First published June 25, 2010;doi:10.1152/ajpheart.00074.2010.-We have generated transgenic rabbits lacking cardiac slow delayed-rectifier K+ current [I-Ks;long QT syndrome type 1 (LQT1)] or rapidly activating delayed-rectifier K+ current [I-Kr;long QT syndrome type 2 (LQT2)]. Rabbits with either genotype have prolonged action potential duration and QT intervals;however, only LQT2 rabbits develop atrioventricular (AV) blocks and polymorphic ventricular tachycardia. We therefore sought to characterize the genotype-specific differences in AV conduction and ventricular refractoriness in LQT1 and LQT2 rabbits. We carried out in vivo electrophysiological studies in LQT1, LQT2, and littermate control (LMC) rabbits at baseline, during isoproterenol infusion, and after a bolus of dofetilide and ex vivo optical mapping studies of the AV node/His-region at baseline and during dofetilide perfusion. Under isoflurane anesthesia, LQT2 rabbits developed infra-His blocks, decremental His conduction, and prolongation of the Wenckebach cycle length. In LQT1 rabbits, dofetilide altered the His morphology and slowed His conduction, resulting in intra-His block, and additionally prolonged the ventricular refractoriness, leading to pseudo-AV block. The ventricular effective refractory period (VERP) in right ventricular apex and base was significantly longer in LQT2 than LQT1 (P < 0.05) or LMC (P < 0.01), with a greater VERP dispersion in LQT2 than LQT1 rabbits. Isoproterenol reduced the VERP dispersion in LQT2 rabbits by shortening the VERP in the base more than in the apex but had no effect on VERP in LQT1. EPS and optical mapping experiments demonstrated

关键词： long QT syndrome His-Purkinje conduction rapidly activating delayed-rectifier potassium current slow delayed-rectifier potassium current transgenic rabbit model pharmacogenomics ventricular effective refractory period dispersion in vivo electrophysiological study

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Complex excitation dynamics underlie polymorphic ventricular tachycardia in a transgenic rabbit model of long QT syndrome type 1

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HEART RHYTHM 2015年第1期12卷 220-228页

作者： Kim, Tae Yun Kunitomo, Yukiko Pfeiffer, Zachary Patel, Divyang Hwang, Jungmin Harrison, Kathryn Patel, Brijesh Jeng, Paul Ziv, Ohad Lu, Yichun peng, xuwen Qu, Zhilin Koren, Gideon Choi, Bum-Rak Brown Univ Cardiovasc Res Ctr Div Cardiol Rhode Island HospWarren Alpert Med Sch Providence RI 02903 USA Univ Pittsburgh Sch Med Cardiovasc Inst Pittsburgh PA USA Univ Rhode Isl Dept Pharmacol Kingston RI 02881 USA Case Western Reserve Univ Sch Med Cleveland OH 44106 USA Penn State Univ Coll Med Dept Comparat Med Hershey PA USA Univ Calif Los Angeles Dept Med Los Angeles CA 90024 USA

BACKGROUND Long QT syndrome type 1 (LQT1) is a congenital disease arising from a loss of function in the slowly activating delayed potassium current I-Ks which causes early afterdepolarizabons (EADs) and polymorphic ventricular tachycardia (pVT). OBJECTIVE The purpose of this study was to investigate the mechanisms underlying pVT using a transgenic rabbit model of LQT1. METHODS Hearts were perfused retrogradely, and action potentials were recorded using a voltage-sensitive dye and CMOS cameras. RESULTS Bolus injection of isoproterenol (140 nM) induced pVT initiated by focal excitations from the right ventricle (RV;n = 15 of 18 pVTs). After the pVT was initiated, complex focal excitations occurred in both the RV and the left ventricle, which caused oscillations of the QRS complexes on ECG, consistent with the recent proposal of multiple shifting foci caused by EAD chaos. Moreover, the action potential upstroke in pVT showed a bimodal distribution, demonstrating the coexistence of 2 types of excitation that interacted to produce complex pVT: Na+ current (I-Na)-mediated fast conduction and L-type Ca2+ current (I-ca)-mediated slow conduction coexist, manifesting as pVT. Addition of 2 mu M tetrodotoxin to reduce I-Na converted pVT into monomorphic VT. Reducing late I-Na in computer simulation converted pVT into a single dominant reentry, agreeing with experimental results. CONCLUSION Our study demonstrates that pVT in LQT1 rabbits is initiated by focal excitations from the RV and is maintained by multiple shifting foci in both ventricles. Moreover, wave conduction in pVT exhibits bi-excitability, that is, fast wavefronts driven by I-Na and slow wavefronts driven by I-ca co-exist during pVT.

关键词： Long QT syndrome Early afterdepolarization Ventricular tachycardia Polymorphic ventricular tachycardia Action potential duration dispersion Optical mapping Bi-excitability

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Ru(II)-base d aggregation-induce d emission (AIE) agents with efficient 1 O2 generation, photo-catalytic NADH oxidation and anticancer activity

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CHINESE CHEMICAL LETTERS 2025年第5期36卷

作者： Xu, Yunli Da, xuwen Wang, Lei peng, Yatong Zhou, Wanpeng Liu, Xiulian Wu, Yao Wang, Wentao Wang, Xuesong Zhou, Qianxiong Chinese Acad Sci Tech Inst Phys & Chem Key Lab Photochem Convers & Optoelect Mat Beijing 100190 Peoples R China Univ Chinese Acad Sci Beijing 100049 Peoples R China Univ Chinese Acad Sci Wenzhou Inst Wenzhou 325000 Peoples R China

Photodynamic therapy (PDT) has received much attention in recent years. However, traditional photosensitizers (PSs) applied in PDT usually suffer from aggregation-caused quenching (ACQ) effect in H2 O, single and inefficient photochemical mechanism of action (MoA), poor cancer targeting ability, etc . In this work, two novel Ru(II)-based aggregation-induced emission (AIE) agents (Ru1 and Ru2) were developed. Both complexes exhibited long triplet excited lifetimes and nearly 100 % singlet oxygen quantum yields in H2 O. In addition, Ru1 and Ru2 displayed potent photo-catalytic reduced nicotinamide adenine dinucleotide (NADH) oxidation activity with turnover frequency (TOF) values of about 1779 and 20 0 0 h-1 , respectively. Therefore, both Ru1 and Ru2 showed efficient PDT activity towards a series of cancer cells. Moreover, Ru2 was further loaded in bovine serum albumin (BSA) to enhance the tumor targeting ability in vivo , and the obtained Ru2@BSA could selectively accumulate in tumor tissues and effectively inhibit tumor growth on a 4T1 tumor-bearing mouse model. So far as we know, this work represents the first report about Ru(II) AIE agents that possess high singlet oxygen quantum yields and also potent photocatalytic NADH oxidation activity, and may provide new ideas for rational design of novel PSs with efficient PDT activity. (c) 2025 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

关键词： Ru(II) complexes Aggregation-induced emission Photo-catalytic NADH oxidation Photodynamic therapy Turnover frequency

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A highly positively charged Ru(II) complex with photo-labile ligands for selective and efficient photo-inactivation of intracellular aureus

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JOURNAL OF INORGANIC BIOCHEMISTRY 2025年 268卷 112908页

作者： Xu, Yunli Da, xuwen Jian, Yao Zhou, Wanpeng Wu, Aifeng Wu, Yao peng, Yatong Liu, Xiulian Shi, Yu Wang, Xuesong Zhou, Qianxiong Chinese Acad Sci Tech Inst Phys & Chem Key Lab Photochem Convers & Optoelect Mat Beijing 100190 Peoples R China Univ Chinese Acad Sci Beijing 100049 Peoples R China

Due to the protection afforded by host cells, intracellular Staphylococcus aureus (S. aureus), particularly methicillin-resistant S. aureus (MRSA), poses a significantly greater challenge to eliminate compared to the extracellular counterparts. It is highly desirable to develop novel antibacterial agents which are capable of selectively and efficiently eradicating intracellular bacteria, including drug-resistant strains, while being less prone to induce bacterial resistance. In this work, two Ru(II) complexes (Ru1 and Ru2) with photo-labile ligands were designed and synthesized. Both Ru1 and Ru2 could covalently bind to DNA after photo-induced ligand dissociation. Compared to Ru1, the incorporation of a triphenylamine group adorned with two positively charged cationic pyridine units significantly boosts the DNA binding constant, bacterial binding/uptake level, and subsequently, the antibacterial activity of Ru2. Ru2 could selectively photo-inactivate intracellular S. aureus and MRSA, being more efficient than vancomycin both in vitro and in vivo. Interestingly, after 20 days' treatment at sublethal concentrations, S. aureus cells exhibited no obvious drug resistance towards Ru2 upon irradiation. Such appealing results may provide new sights for developing novel antibacterial agents against intractable intracellular pathogens and also prevalent drug resistance.

关键词： Ru(II) complexes Photo-induced ligand dissociation Intracellular bacteria DNA binding Drug resistance

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Recent advances in bubble-based technologies: Underlying interaction mechanisms and applications

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APPLIED PHYSICS REVIEWS 2021年第1期8卷

作者： Qiao, Chenyu Yang, Diling Mao, Xiaohui Xie, Lei Gong, Lu peng, xuwen peng, Qiongyao Wang, Tao Zhang, Hao Zeng, Hongbo Univ Alberta Dept Chem & Mat Engn Edmonton AB T6G 1H9 Canada

Gas bubbles widely exist in nature and numerous industrial processes. The physicochemical characteristics of bubbles such as large specific surface area, low density, and hydrophobicity make them an ideal platform for developing colloidal and interfacial technologies. Over the past few decades, much effort has been devoted to investigating the properties and behaviors of bubbles and their applications. A series of bubble-based technologies (BBTs) have been developed, which have attracted increasing attention and shown great importance in a wide range of engineering, material, and biological fields. These BBTs, such as bubble flotation and the bubble-liposome system, provide feasible and promising solutions to mineral separation, material assembling, medical diagnosis, and drug delivery. In this work, we have systematically reviewed the physicochemical characteristics of bubbles and how to modulate their behaviors in complex fluid systems, as well as the underlying fundamental interaction mechanisms of bubbles in related BBTs. Advanced nanomechanical techniques such as atomic force microscopy, which are used to quantify the interaction mechanisms in bubble-containing systems, have been introduced. The effects of various influential factors on the bubble behaviors are discussed, which provide potential approaches to improve the controllability and performance of BBTs. The recent advances in the applications of selected BBTs in engineering, biomedical, and material areas are presented. Some remaining challenging issues and perspectives for future studies have also been discussed. This review improves the fundamental understanding of characteristics and surface interaction mechanisms of bubbles, with useful implications for developing advanced BBTs.

关键词： Diagnosis

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HClO-responsive dinuclear Ru(II) complexes for selective imaging and efficient photo-inactivation of intracellular bacteria

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CHINESE CHEMICAL LETTERS 2025年第6期36卷

作者： Zhou, Wanpeng Da, xuwen Xu, Yunli peng, Yatong Liu, Xiulian Wu, Yao Shi, Yu Wu, Aifeng Yao, Yishan Wang, Xuesong Zhou, Qianxiong Chinese Acad Sci Key Lab Photochem Convers & Optoelect Mat Tech Inst Phys & Chem Beijing 100190 Peoples R China Univ Chinese Acad Sci Beijing 100049 Peoples R China Beijing Inst Pharmacol & Toxicol Beijing 100850 Peoples R China

Intracellular bacteria (ICB), cloaked by the protective barriers of host cells, pose a formidable challenge to selective and efficient eradication. The employment of activatable photosensitizers based antibacterial photodynamic therapy (aPDT) holds significant potential for selective imaging and photo-inactivation of ICB while minimizing side effects on normal cells. Drawing inspiration from the elevated hypochlorous acid (HClO) levels in ICB infected phagocytes, herein we firstly designed and synthesized a series of HClOresponsive dinuclear Ru(II) complexes (Ru1-Ru3) to achieve such a goal. Initially, the luminescence, 1 O2 generation and aPDT activity of these Ru(II) complexes were suppressed due to the quenching effect of the azo group, but were recovered after reaction with HClO in solutions or within ICB infected phagocytes. The detailed results revealed that Ru1 and Ru3 could not only selectively visualize ICB, but also demonstrated remarkable aPDT activity against ICB, surpassing vancomycin both in vitro and in vivo . (c) 2025 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

关键词： Intracellular bacteria HClO-responsive Ru(II) complexes Antibacterial photodynamic therapy Selective imaging and photo-inactivation

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Decreased intestinal abundance of Akkermansia muciniphila is associated with metabolic disorders among people living with HIV

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ANNALS OF MEDICINE 2025年第1期57卷 2474730页

作者： Qian, Zhe Chen, Suling Liao, Xiaoyang Xie, Jingfang Xu, Yuyuan Zhong, Huiqun Ou, Lang Zuo, Xiang Xu, xuwen peng, Jie Wu, Jian Cai, Shaohang Southern Med Univ Guangdong Prov Peoples Hosp Guangdong Acad Med Sci Guangdong Prov Geriatr InstDept Elderly Resp 2 Guangzhou 510030 Peoples R China Southern Med Univ Nanfang Hosp Dept Infect Dis Guangzhou 510515 Peoples R China Southern Med Univ Guangdong Prov Peoples Hosp Guangdong Acad Med Sci Guangdong Prov Geriatr InstDept Geriatr Guangzhou Peoples R China Univ South China Affiliated Nanhua Hosp Dept Hepatobiliary Surg Hengyang Peoples R China Southern Med Univ Nanfang Hosp Dept Gen Surg Div Hepatobiliopancreat Surg Guangzhou Peoples R China South China Univ Technol Sch Med Guangzhou Peoples R China

BackgroundPrevious studies have shown changes in gut microbiota after human immunodeficiency virus (HIV) infection, but there is limited research linking the gut microbiota of people living with HIV (PLWHIV) to metabolic *** total of 103 PLWHIV were followed for 48 weeks of anti-retroviral therapy (ART), with demographic and clinical data collected. Gut microbiome analysis was conducted using metagenomic sequencing of fecal samples from 12 individuals. Nonalcoholic fatty liver disease (NAFLD) was diagnosed based on controlled attenuation parameter (CAP) values of 238 dB/m from liver fibro-scans. Participants were divided based on the presence of metabolic disorders, including NAFLD, overweight, and hyperlipidemia. Akkermansia abundance in stool samples was measured using RT-qPCR, and Pearson correlation and logistic regression were applied for *** sequencing revealed a significant decline in gut Akkermansia abundance in PLWHIV with NAFLD. STAMP analysis of public datasets confirmed this decline after HIV infection, while KEGG pathway analysis identified enrichment of metabolism-related genes. A prospective cohort study with 103 PLWHIV followed for 48 weeks validated these findings. Akkermansia abundance was significantly lower in participants with NAFLD, overweight, and hyperlipidemia at baseline, and it emerged as an independent predictor of NAFLD and overweight. Negative correlations were observed between Akkermansia abundance and both CAP values and body mass index (BMI) at baseline and at week 48. At the 48-week follow-up, Akkermansia remained a predictive marker for *** abundance was reduced in PLWHIV with metabolic disorders and served as a predictive biomarker for NAFLD progression over 48 weeks of ART.

关键词： HIV gut microbiota metabolic diseases NAFLD overweight Akkermansia muciniphila

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降低铅银渣含锌的研究与实践

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湖南有色金属 2023年第4期39卷 33-35页

作者：彭许文南丹县南方金属有限责任公司广西南丹547000

通过加强多膛炉操作,降低氧化锌中的不溶锌含量,过程中加强球磨矿浆粒度、温度、酸度与反应时间的控制,可以大幅降低铅银渣含锌,不但可以降低损失、创造效益,也为后续铅银渣进入铅冶炼系统处理创造了良好的条件。

关键词：锌浸出渣多膛炉不溶锌中性浸出酸性浸出铅银渣 ZnS

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Probing the surface forces between air bubbles and bitumen via direct force Measurements: Effects of aqueous chemistry

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FUEL 2024年第PartC期357卷

作者： Yang, Diling Qiao, Chenyu Mao, Xiaohui Wang, Jingyi Xie, Lei Chen, Jingsi peng, xuwen peng, Qiongyao Wang, Tao Liu, Qi Zhang, Hao Zeng, Hongbo Univ Alberta Dept Chem & Mat Engn Edmonton AB T6G 1H9 Canada

The surface interactions of air bubbles and other components (e.g., particles, oil droplets) significantly influence the operation efficiency of a variety of engineering processes such as oily water treatment, bitumen extraction and flotation. Herein, the surface interactions of air bubbles with two types of Athabasca bitumen samples in aqueous solutions of varying pH, salinity, type of cations and in the presence of surfactants have been systematically characterized using a bubble probe atomic force microscope (AFM) technique. AFM imaging has revealed that exposure to high concentrations of NaCl and CaCl2 solutions or alkaline environments causes roughening of the bitumen surfaces. The results of surface force measurements demonstrate that the interaction and attachment behaviors between bubbles and bitumen are significantly affected by ionic strength, solution pH, and the presence of surfactants. The experimental force measurement results could be accurately described by a theoretical model that incorporates Reynolds lubrication theory and augmented Young-Laplace equation, with the inclusion of disjoining pressure. In low-salinity conditions, the bubble-bitumen interaction is dominated by electric double layer (EDL) repulsion, which prevents surface attachment. This effect is more pronounced at elevated pH conditions. In high-salinity solutions, however, the EDL interactions are significantly reduced, and the hydrophobic interaction becomes the dominant factor, overcoming the van der Waals repulsion and leading to the attachment of bubbles to bitumen surfaces. Raising aqueous pH weakens the bubble-bitumen hydrophobic interaction, whereas the introduction of calcium ions strengthens this interaction, resulting in enhanced surface attachment. Interestingly, even in high-salinity conditions, the presence of a small number of surfactants can inhibit bubble-bitumen contact, mainly caused by reduced hydrophobic attraction and increased steric repulsion. This work provid

关键词： bitumen oil sands bitumen flotation bubbles surface interactions

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