Subjectivity
·
2024
·Vol. 31
·期 1
·97-116
·
IF 0.7
Gilbert Bennett
Examining the author’s own experiences of narcotics addiction reveals certain aspects of the addicted mentality that have strong ethical valence. In general, this shows that addiction is not a state fundamentally characterized by lack. The rudiments of this position are found in some contemporary philosophy of addiction; also, it is contrasted with a common widely held mistaken view. Addiction should instead be understood in continuity with and as illuminating the nature of human personhood and subjectivity. Under a phenomenology specific to the author’s experience, addiction appears as a mode of experience that has an unmanageable overflow of narratives created as discourses concerning people, events, thoughts, and feelings; narratives embodied in assemblages of objects; and narratives appearing as mental images. These considerations suggest that pre-reflective connection to the world can be profoundly illuminative but also can isolate is from the world and, further, that our ethical values form from within our lives and not as an artificial addition. Our historical, narrative self-understanding has existential and moral import. Thus, addiction by its extremity exemplifies the ceaseless ethical activity of personhood.
研究领域:
成瘾哲学
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现象学
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伦理学
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心灵哲学
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叙事身份
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DOI
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Bingyong Lin,Yuanyuan Yao,Yueliang Wang,Lifen Chen,Xianghong Peng,Longhua Guo
The nicotine addiction problem is of great concern, particularly in adolescents. Notably, nicotine addiction drives humans to continue smoking. Notably, several diseases and disorders are caused by smoking. To date, various adsorbents have been proposed to develop a functionalization filter tip for reducing nicotine content in mainstream smoke. However, the nicotine adsorption efficiencies of most of the reported functionalization filter tips were not satisfactory, and their preparation process was complex and time-consuming. Herein, we demonstrate a highly active and adsorbing filter tip for cigarettes, fabricated by decorating polydopamine (PDA) on the surface of a commercial filter tip in situ. The PDA coating on the filter tip was obtained by the self-polymerization of dopamine (DA) within 16 h, which was quicker and easier than the preparation processes of other reported functionalized filter tips. Significantly, the PDA-decorated filter tip had a nicotine adsorption efficiency as high as ∼95%, which was much higher than most of the commercial filter tips.
研究领域:
烟草科学
·
材料科学
·
公共卫生
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Yunfan Chen,Haitao Li,Jing Shi,Jiajun Cheng,Zhuolu Song,Xinyue Zhang,Xinnan Li,Jialin Zhuang,Qi An,Zeguo Feng,Long Wang
Opioids addiction has been steadily rising worldwide, posing serious medical and social challenges. However, there is currently no gold standard for diagnosing opioid addiction for the lack of a specific biomarker. Surface-enhanced Raman scattering (SERS) is widely employed in screening complex components for its capacity to present fingerprint features in the spectra. However, it remains challenging to test blood samples to diagnose diseases without biomarkers using SERS. Here, we introduce a machine learning (ML) assisted, SERS-based platform for analysis of serum of addiction mouse, enabling the diagnosis of morphine and fentanyl addiction. We identify that the proper ligand choice during preparation of the SERS substrate is essential for obtaining clear signal from blood samples. Among several capping ligands, only sodium citrate leads to successful SERS substrate fabrication being able to test blood samples. The critical role of the citrate ligand to promote adsorption and charge transfer between the substrate and the biomolecule of interest is demonstrated. Accuracy rates up to 100% and 87% are achieved for morphine addiction and fentanyl addiction analyses. The present work paves a new way achieving clinical label-free serum diagnosis of morphine and fentanyl addiction by SERS with machine learning, showing its potential for fast-screening of diseases without a clear biomarker.
研究领域:
医学诊断
·
生物化学
·
人工智能应用
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产品关联
DOI
高影响因子
JOURNAL OF MOLECULAR NEUROSCIENCE
·
2025
·Vol. 75
·期 3
·1-14
·
IF 2.7
Fan Weihao,Ye Yi,Yang Hongkun,Wei Ying,Shi Kaiting,Yang Xinyu,Li Jian,Wang Zilong,Sun Yiming,Liao Linchuan
Ketamine is a synthesized anesthetic drug that was used extensively as a surgical anesthetic in the 1960s. Currently, ketamine is being investigated extensively for its potential as a treatment for depression. However, the addictive nature of ketamine has become an issue that cannot be ignored at this stage. As of now, there is no clear understanding of the changes in striatal metabolites and their relative metabolic pathways under the addictive effect of ketamine. In this study, a stable model of ketamine-induced conditioned place preference (CPP) was established. Non-targeted metabolomics and targeted metabolomics techniques, based on the ultra-performance liquid chromatography-Q Exactive hybrid quadrupole-Orbitrap mass spectrometry (UHPLC-QE/MS) and the UHPLC-MS platform, were employed to uncover the metabolic characteristics and neurotransmitter profiles of the striatum after ketamine abuse in mice. Potential biomarkers and related differential metabolic pathways of this model have been revealed. In non-targeted metabolomics analysis, striatal differential metabolites mainly involve pathways related to arginine synthesis, purine metabolism, and morphine addiction. In targeted metabolism, the striatum of mice receiving ketamine showed an increase in the content of the neurotransmitter kynurenine (Kyn) and a decrease in the content of the neurotransmitter dopamine (DA). Our study suggested that Kyn and DA metabolism disturbances might be associated with ketamine-induced CPP phenotypes and provided a new perspective for investigating the addiction mechanisms of ketamine.
研究领域:
药理学
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神经科学
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代谢组学
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精神病学
·
分析化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NEUROSCIENCE
·
2025
·
IF 4
Tianyi Yang,Yan Chen,Maolin Wang,Ren Ren,Fang Yan,Peng Xu,Bin Di
Nitrous oxide use Disorder（NUD）has recently received increasing social concern for its sharp rise among young people. However, the underlying mechanisms of NUD remain largely unexplored, which obstructs treatment strategy development and may exacerbate the epidemic of N2O abuse. Thus, specifying the essential mechanisms and targets in NUD are desperately needed. Here we unveiled a series of molecular adaptations regarding N2O reward memory in Nucleus accumbens (NAc) of mice through multi-omics approaches comprising transcriptomics, proteomics, metabolomics approaches. Our miRNA transcriptomics and pull-down proteomics analyzes uncovered that miR-7220-5p regulated N2O-induced conditioned-place preference (CPP) and associated increase of dendritic spine density in NAc of male mice. Our pull-down proteomics and metabolomics analyzes revealed that miR-7220-5p modulated ERK signaling pathway by directly binding with NR2B receptor. In summary, our work confirmed that restoring miR-7220-5p expression in NAc protected against synaptic abnormality via the NR2B/ERK/CREB signaling, thereby attenuating CPP behaviors in NUD. Selective inhibition of NR2B or ERK signaling blocked the reward memory of N2O-CPP via NAc microinjection. Our study proposed a potential therapeutic strategy for NUD and provided comprehensive resources of biological data to support future investigations of NUD treatment.Significance Statement Nitrous oxide Use Disorder (NUD) has recently received tremendously increasing social concern for its sharp rise among young people. Although the neurological consequences and their etiologies of consuming N2O have been well elucidated, the underlying mechanisms of NUD remain largely unexplored, which obstructs the development of clinical treatment strategies and may exacerbate the epidemic of N2O abuse. Our work uncovered the role of miR-7220-5p/NR2B/ERK/CREB signaling against synaptic abnormality/CPP behaviors. Selective inhibition of NR2B or ERK signaling blocked the reward memory of N2O-CPP via NAc microinjection. Our study proposed therapeutic targets for overcoming NUD behaviors and the omics data provided comprehensive biological resources to support future investigations of NUD.
研究领域:
神经科学
·
分子生物学
·
药理学
·
生物信息学
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精神病学
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细胞信号传导
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成瘾研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Yukun Huang,Yu Chen,Songlei Zhou,Laozhi Xie,Kaifan Liang,Jianpei Xu,Qian Zhang,Huan Chen,Dayuan Wang,Qingxiang Song,Gan Jiang,Ni Mei,Fenfen Ma,Huiping Lu,Xiaoling Gao,Jun Chen
Metabolic therapy targeting the metabolic addictions driven by gain-of-function mutations in KRAS is promising in fighting cancer through selective killing of malignant cells without hurting healthy cells. However, metabolic compensation and heterogeneity make current metabolic therapies ineffective. Here, we proposed a biomimetic “Nutri-hijacker” with “Trojan horse” design to induce synthetic lethality in KRAS-mutated (mtKRAS) malignant cells by hitchhiking and reprogramming the metabolic addictions. Nutri-hijacker consisted of the biguanide-modified nanoparticulate albumin that impaired glycolysis and a flavonoid that restrained glutaminolysis after the macropinocytosis of Nutri-hijacker by mtKRAS malignant cells. Nutri-hijacker suppressed the proliferation and spread of mtKRAS malignant cells while lowering tumor fibrosis and immunosuppression. Nutri-hijacker significantly extended the lifespan of pancreatic ductal adenocarcinoma (PDAC)-bearing mice when combined with the hydroxychloroquine-based therapies that failed in clinical trials. Collectively, our findings demonstrated that Nutri-hijacker is a strong KRAS mutation-customized inhibitor and the synthetic lethality based on mtKRAS-driven metabolic addictions might be a promising strategy against PDAC.
研究领域:
肿瘤学
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分子生物学
·
癌症治疗
·
药理学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2021
·
IF 15.881
Chen-Song Huang,Qiong-Cong Xu,Chunlei Dai,Liying Wang,Yi-Chih Tien,Fuxi Li,Qiao Su,Xi-Tai Huang,Jun Wu,Wei Zhao,Xiao-Yu Yin
Gallbladder cancer (GBC) is the most aggressive malignancy of the biliary tract cancer, and there is a lack of effective treatment. Here, we developed a nanoparticle platform (8P4 NP) that can deliver THZ1, a cyclin-dependent kinase 7 (CDK7) inhibitor, to treat GBC. Analysis of datasets demonstrated that CDK7 was positively correlated with poor prognosis. CDK7 inhibition suppressed cell proliferation, induced apoptosis, and caused cell cycle block in GBC cells. THZ1 downregulated CDK7-mediated phosphorylation of RNA polymerase II (RNAPII), resulting in a significant downregulation of transcriptional programs, with a preferential repression of oncogenic transcription factors. To improve the tumor targeting efficiency of THZ1, 8P4 NPs were prepared and assembled with THZ1 to form THZ1@8P4 NPs. Compared with free THZ1, THZ1@8P4 NPs showed more advantages in prolonging blood circulation, escaping from lysosomes and increasing cellular uptake. Importantly, THZ1@8P4 NPs demonstrated a more significant inhibition effect on GBC cells than free THZ1 in vitro. In addition, THZ1@8P4 NPs could efficiently deliver THZ1 to tumor sites in a patient-derived xenograft model of early recurrence, leading to tumor regression and transcriptional inhibition with minimal toxicity. In summary, we conclude that THZ1@8P4 NPs provide a potent therapeutic strategy that targets CDK7-mediated transcriptional addiction in GBC.
研究领域:
肿瘤学
·
药理学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Chenxing Xu,Nan Wang,Tao Ma,Shengrong Pei,Meiting Wang,Jinpeng Yu,Dongting Zhangsun,Xiaopeng Zhu,Sulan Luo
α 3 β 4, a vital subtype of neuronal nicotinic acetylcholine receptors (nAChRs), is widely distributed in the brain, ganglia, and adrenal glands, associated with addiction and neurological diseases. However, the lack of specific imaging tools for α 3 β 4 nAChRs has hindered the investigation of their tissue distribution and functions. [D11A]LvIA, a peptide derived from marine cone snails, demonstrates high affinity and potency for α 3 β 4 nAChRs, making it a valuable pharmacological tool for studying this receptor subtype. In this study, three fluorescent conjugates of [D11A]LvIA were synthesized using 6-TAMRA-SE (R), Cy3-NHS-ester (Cy3), and BODIPY-FL NHS ester (BDP) dyes. The electrophysiological activities were assessed in Xenopus laevis oocytes by two-electrodes voltage clamp (TEVC). [D11A]LvIA-Cy3 and [D11A]LvIA-BDP show improved selectivity and affinity, with IC 50 values of 512.70 nM and 343.50 nM, respectively, and [D11A]LvIA-Cy3 exhibits better stability in cerebrospinal fluid. Utilizing [D11A]LvIA-Cy3, we successfully visualized the distribution of α 3 β 4 nAChRs in rat trigeminal ganglia, retina, adrenal glands, and various brain regions. This novel fluorescent peptide provides a significant pharmacological tool for the exploration and visualization in-situ distribution of α 3 β 4 nAChRs in different tissues and also assists in clarifying the function.
研究领域:
神经科学
·
药理学
·
成像技术
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产品关联
DOI
PubMed
高影响因子
Neural Regeneration Research
·
2024
·Vol. 19
·期 10
·2270
·
IF 5.9
Qi Yize,Zhou Yao,Li Jiyang,Zhu Fangyuan,Guo Gengni,Wang Can,Yu Man,Wang Yijie,Ma Tengfei,Feng Shanwu,Zhou Li
Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.
研究领域:
神经科学
·
药理学
·
炎症
·
成瘾
·
行为神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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