MRI-based Machine Learning Radiomics Can Predict CSF1R Expression Level and Prognosis in High-grade Gliomas.

The purpose of this study is to predict the mRNA expression of CSF1R in HGG non-invasively using MRI (magnetic resonance imaging) omics technology and to evaluate the correlation between the established radiomics model and prognosis. We investigated the predictive value of CSF1R in the Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA) database. The Support vector machine (SVM) and the Logistic regression (LR) algorithms were used to create a radiomics_score (Rad_score), respectively. The effectiveness and performance of the radiomics model was assessed in the training (n = 89) and tenfold cross-validation sets. We further analyzed the correlation between Rad_score and macrophage-related genes using Spearman correlation analysis. A radiomics nomogram combining the clinical factors and Rad_score was constructed to validate the radiomic signatures for individualized survival estimation and risk stratification. The results showed that CSF1R expression was markedly elevated in HGG tissues, which was related to worse prognosis. CSF1R expression was closely related to the abundance of infiltrating immune cells, such as macrophages. We identified nine features for establishing a radiomics model. The radiomics model predicting CSF1R achieved high AUC in training (0.768 in SVM and 0.792 in LR) and tenfold cross-validation sets (0.706 in SVM and 0.717 in LR). Rad_score was highly associated with tumor-related macrophage genes. A radiomics nomogram combining the Rad_score and clinical factors was constructed and revealed satisfactory performance. MRI-based Rad_score is a novel way to predict CSF1R expression and prognosis in high-grade glioma patients. The radiomics nomogram could optimize individualized survival estimation for HGG patients.

Hippocampus Glutathione S Reductase Potentially Confers Genetic Resilience to Cognitive Decline in the AD-BXD Mouse Population.

Alzheimer's disease (AD) is a prevalent and costly age-related dementia. Heritable factors account for 58-79% of variation in late-onset AD, but substantial variation remains in age-of- onset, disease severity, and whether those with high-risk genotypes acquire AD. To emulate the diversity of human populations, we utilized the AD-BXD mouse panel. This genetically diverse resource combines AD genotypes with multiple BXD strains to discover new genetic drivers of AD resilience. Comparing AD-BXD carriers to noncarrier littermates, we computed a novel quantitative metric for resilience to cognitive decline in the AD-BXDs. Our quantitative AD resilience trait was heritable and genetic mapping identified a locus on chr8 associated with resilience to AD mutations that resulted in amyloid brain pathology. Using a hippocampus proteomics dataset, we nominated the mitochondrial glutathione S reductase protein (GR or GSHR) as a resilience factor, finding that the DBA/2J genotype was associated with substantially higher GR abundance. By mapping protein QTLs (pQTLs), we identified synaptic organization and mitochondrial proteins coregulated in trans with a cis-pQTL for GR. We found four coexpression modules correlated with the quantitative resilience score in aged 5XFAD mice using paracliques, which were related to cell structure, protein folding, and postsynaptic densities. Finally, we found significant positive associations between human GSR transcript abundance in the brain and better outcomes on AD-related cognitive and pathology traits in the Religious Orders Study/Memory and Aging project (ROSMAP). Taken together, these data support a framework for resilience in which neuronal antioxidant pathway activity provides for stability of synapses within the hippocampus.

ZCCHC17 Modulates Neuronal RNA Splicing and Supports Cognitive Resilience in Alzheimer's Disease.

ZCCHC17 is a putative master regulator of synaptic gene dysfunction in Alzheimer's disease (AD), and ZCCHC17 protein declines early in AD brain tissue, before significant gliosis or neuronal loss. Here, we investigate the function of ZCCHC17 and its role in AD pathogenesis using data from human autopsy tissue (consisting of males and females) and female human cell lines. Co-immunoprecipitation (co-IP) of ZCCHC17 followed by mass spectrometry analysis in human iPSC-derived neurons reveals that ZCCHC17's binding partners are enriched for RNA-splicing proteins. ZCCHC17 knockdown results in widespread RNA-splicing changes that significantly overlap with splicing changes found in AD brain tissue, with synaptic genes commonly affected. ZCCHC17 expression correlates with cognitive resilience in AD patients, and we uncover an APOE4-dependent negative correlation of ZCCHC17 expression with tangle burden. Furthermore, a majority of ZCCHC17 interactors also co-IP with known tau interactors, and we find a significant overlap between alternatively spliced genes in ZCCHC17 knockdown and tau overexpression neurons. These results demonstrate ZCCHC17's role in neuronal RNA processing and its interaction with pathology and cognitive resilience in AD, and suggest that the maintenance of ZCCHC17 function may be a therapeutic strategy for preserving cognitive function in the setting of AD pathology.

A longitudinal resource for population neuroscience of school-age children and adolescents in China.

During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), the first ten-year stage of the lifespan CCNP (2013-2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community ( https://ccnp.scidb.cn ) at the Science Data Bank.

Accelerating the Design of Self-Guided Microrobots in Time-Varying Magnetic Fields.

Mobile robots combine sensory information with mechanical actuation to move autonomously through structured environments and perform specific tasks. The miniaturization of such robots to the size of living cells is actively pursued for applications in biomedicine, materials science, and environmental sustainability. Existing microrobots based on field-driven particles rely on knowledge of the particle position and the target destination to control particle motion through fluid environments. Often, however, these external control strategies are challenged by limited information and global actuation where a common field directs multiple robots with unknown positions. In this Perspective, we discuss how time-varying magnetic fields can be used to encode the self-guided behaviors of magnetic particles conditioned on local environmental cues. Programming these behaviors is framed as a design problem: we seek to identify the design variables (e.g., particle shape, magnetization, elasticity, stimuli-response) that achieve the desired performance in a given environment. We discuss strategies for accelerating the design process using automated experiments, computational models, statistical inference, and machine learning approaches. Based on the current understanding of field-driven particle dynamics and existing capabilities for particle fabrication and actuation, we argue that self-guided microrobots with potentially transformative capabilities are close at hand.

Worlds apart? Testing the cultural distance hypothesis in music perception of Chinese and Western listeners.

According to the cultural distance hypothesis (CDH), individuals learn culture-specific statistical structures in music as internal stylistic models and use these models in predictive processing of music, with musical structures closer to their home culture being easier to predict. This cultural distance effect may be affected by domain-specific (musical ability) and domain-general individual characteristics (openness, implicit cultural bias). To test the CDH and its modulation by individual characteristics, we recruited Chinese and Western adults to categorize stylistically ambiguous and unambiguous Chinese and Western melodies by cultural origin. Categorization performance was better for unambiguous (low CD) than ambiguous melodies (high CD), and for in-culture melodies regardless of ambiguity for both groups, providing evidence for CDH. Musical ability, but not other traits, correlated positively with melody categorization, suggesting that musical ability refines internal stylistic models. Therefore, both cultures show musical enculturation in their home culture with a modulatory effect of individual musical ability.

Mechanosensitive Ion Channel TMEM63A Gangs Up with Local Macrophages to Modulate Chronic Post-amputation Pain.

Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain (CPAP). However, the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG, and the expression of TMEM63A increased significantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer (TNT). Behavioral tests showed that the mechanical, heat, and cold sensitivity were not affected in the Tmem63a-/- mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a-/- mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.

Amentoflavone Exerts Anti-Neuroinflammatory Effects by Inhibiting TLR4/MyD88/NF-κB and Activating Nrf2/HO-1 Pathway in Lipopolysaccharide-Induced BV2 Microglia.

Background: Amentoflavone, a natural biflavone, exerts anti-inflammation, antioxidation, and antiapoptosis effects on many diseases. However, the mechanism of amentoflavone on neuroinflammation-related diseases has not been comprehensively examined clearly. Methods: BV2 microglial cells were treated with amentoflavone (10 µM), followed by lipopolysaccharide (LPS). Microglial activation and migration ability and the expression of proinflammatory cytokines and other signaling proteins were determined using immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay, and wound-healing assays. Results: Amentoflavone restored LPS-induced microglia activation, migration, and inflammation response which depends on regulating toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) pathway. In addition, amentoflavone also enhanced nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) levels in LPS-treated BV2 microglial cells. Conclusions: Amentoflavone ameliorated LPS-induced neuroinflammatory response and oxidative stress in BV2 microglia. These data provide new insight into the mechanism of amentoflavone in the treatment of neuroinflammation-related diseases. Therefore, amentoflavone may be a potential therapeutic option for neurological disorders.

Traditional Chinese medicine injections: where we are after 80-year development.

Traditional Chinese medicine (TCM) injection is the combination of modern pharmaceutical technology and traditional Chinese prescription, which was born in 1941 and played a great role in the backward medical conditions at that time. However, the debate over TCM injections has never stopped due to adverse drug reactions (ADRs). The regulation on TCM injections has been further strengthened since 2017, which has prompted many TCM injections to carry out re-evaluations on quality, safety, efficiency as well as pharmacoeconomics, which made significant changes and progress. This review presented an up-to-date analysis of the types, amounts, and ADRs of TCM injections based on the published data and literature. This review also summarized the potential reasons for the ADRs and re-evaluation strategies. This review will provide some useful clues for TCM injections and their clinical use.

ATP-binding cassette protein ABCA7 deficiency impairs sphingomyelin synthesis, cognitive discrimination, and synaptic plasticity in the entorhinal cortex.

Sphingomyelin (SM) is an abundant plasma membrane and plasma lipoprotein sphingolipid. We previously reported that ATP-binding cassette family A protein 1 (ABCA1) deficiency in humans and mice decreases plasma SM levels. However, overexpression, induction, downregulation, inhibition, and knockdown of ABCA1 in human hepatoma Huh7 cells did not decrease SM efflux. Using unbiased siRNA screening, here, we identified that ABCA7 plays a role in the biosynthesis and efflux of SM without affecting cellular uptake and metabolism. Since loss of function mutations in the ABCA7 gene exhibit strong associations with late-onset Alzheimer's disease across racial groups, we also studied the effects of ABCA7 deficiency in the mouse brain. Brains of ABCA7-deficient (KO) mice, compared with WT, had significantly lower levels of several SM species with long chain fatty acids. In addition, we observed that older KO mice exhibited behavioral deficits in cognitive discrimination in the active place avoidance task. Next, we performed synaptic transmission studies in brain slices obtained from older mice. We found anomalies in synaptic plasticity at the intracortical synapse in layer II/III of the lateral entorhinal cortex but not in the hippocampal CA3-CA1 synapses in KO mice. These synaptic abnormalities in KO brain slices were rescued with extracellular SM supplementation but not by supplementation with phosphatidylcholine. Taken together, these studies identify a role of ABCA7 in brain SM metabolism and the importance of SM in synaptic plasticity and cognition, as well as provide a possible explanation for the association between ABCA7 and late-onset Alzheimer's disease.

Observation of the Antimicrobial Activities of Two Actinomycetes in the Harvester Ant Messor orientalis.

Observations have shown that seeds collected by harvester ants are less likely to mold. Based on evolutionary analysis and other research, it was hypothesized that harvester ants could apply actinomycetes to protect seeds, similar to the protection of mutualistic fungi by leafcutter ants. Two actinomycetes were successfully isolated from the harvester ant Messor orientalis. The taxonomic status of the actinomycetes was determined by 16S rRNA sequence analysis and biochemical experimental observations. Their inhibitory effects on plant pathogens were measured. One of the bacteria was identified as Brachybacterium phenoliresistens and denoted as B. phenoliresistens MO. The other belonged to the genus Microbacterium. It was named Microbacterium sp. Growth rate determination and coculture experiments were performed to explore the inhibitory effect of actinomycetes on indicator plant pathogens. The inhibition rates of the actinomycetes toward Peronophythora litchii and Rhizoctonia solani were 100% in media containing 30% or more fermentation broth, and they also showed an inhibitory effect on Colletotrichum siamense. The coculture experiment supported this result by showing that the growth of P. litchii and R. solani was inhibited in the presence of actinomycetes. Therefore, the results of this study show the agricultural application potential of these bacteria and may provide a reference for research on the symbiosis of harvester ants with actinomycetes.

Ultrasound-Guided Extraforaminal Thoracic Nerve Root Block Through the Midpoint of the Inferior Articular Process and the Parietal Pleura: A Clinical Application of Thoracic Paravertebral Nerve Block.

PURPOSE: Thoracic nerve root (TNR) block is performed primarily under computed tomography or X-ray fluoroscopy but is associated with radiation exposure. Ultrasound requires no radiation and distinguishes vessels, nerves, pleura, and other tissues. Few reports of ultrasound-guided TNR (US-TNR) block have been described, and the puncture end point has not been clearly defined. Herein, we evaluated the feasibility of US-TNR block using the midpoint of the inferior articular process (IAP) and parietal pleura (PP) as the puncture end point. PATIENTS AND METHODS: A prospective series of 10 patients with Herpes Zoster-associated pain underwent US-TNR-guided block performed using an in-plane technique with the midpoint of thoracic IAP and PP as the puncture end points of ultrasonography. The US-TNR block procedure was performed with ultrasound as the primary imaging tool followed by fluoroscopic confirmation. RESULTS: In all patients, the needle tips were visible at the lateral margin of the pedicle in the anteroposterior view and at the extraforaminal zone in the lateral view. The TNR and dorsal root ganglion (DRG) were delineated in all 10 patients. Furthermore, 2 mL of radiopaque agent could delineate the epidural space in 8 patients and the thoracic paravertebral (TPV) space in the other 2 patients. All patients developed numbness along the corresponding dermatome 30 min after injection of local anesthetics. The numeric rating scale (NRS) score at baseline, and at two- and four-week follow-ups were 6.50 ± 1.35, 3.50 ± 0.85 (vs NRS at baseline, P < 0.01), and 4.00 ± 0.82 (vs NRS at baseline, P < 0.01), respectively. CONCLUSION: This study demonstrated the feasibility of US-TNR block using the in-plane technique with the midpoint of thoracic IAP and PP as the puncture end point to effectively block the TNR and DRG. This technique is an accurate clinical application of TPV nerve block and provides a potential therapeutic option for the treatment of neuropathic pain.

Dual antisense oligonucleotide targeting miR-21/miR-155 synergize photodynamic therapy to treat triple-negative breast cancer and inhibit metastasis.

Triple negative breast cancer (TNBC) is a greatly aggressive subtype of breast cancer with high recurrence and mortality rates. Chemotherapy as a primary treatment for cancer is limited due to toxic side effects and drug resistance. Therefore, low toxicity and more effective breast cancer therapeutic approaches are greatly desired. In this study, a strategy which using ZIF-90 nanoparticles co-deliver Ce6-anti-miR-21 and Ce6-anti-miR-155 into the tumor cells was developed. Due to the pH responsive drug release of ZIF-90, antisense oligonucleotides (anti-miRNAs) and photosensitizers are able to be efficiently released inside tumor microenvironment. The nano delivery system captures overexpressed oncogenic miRNAs while the photosensitizer Ce6 generates ROS under light irradiation to effectively induce the apoptosis of tumor cell. This combinatorial effect was verified by results showing that the purposed therapic method could effectively inhibit tumor cell proliferation and metastasis. The concept of antisense oligonucleotide combined with photodynamic therapy has great potential in cancer treatment or adjuvant therapy.

Modification of surface morphology of hydrogels due to subsurface femtosecond laser micromachining.

In this paper, we studied the effects of subsurface femtosecond laser micromachining on surface morphology in hydrogels. Depending on material properties and writing conditions, we found surface bumps when materials were hydrated, and trenches when they were dehydrated, which can be attributed to the localized change in water concentration. Such wavy surfaces by laser-induced refractive index change are not desirable in clinical contact lenses. Therefore, the minimization of surface bumps is necessary to ensure the user eye wearing comfort. In addition, we examined the optical effects of the surface features using interferometry and the surface morphology using profilometry. Finally, we proposed a simplified mechanical model based on localized swelling.

Development and validation of a ferroptosis-related model for three digestive tract tumors based on a pan-cancer analysis.

Aims: To develop a ferroptosis gene-based survival-predictor model for predicting the prognosis of patients with digestive tract tumors, a pan-caner analysis was performed. Materials & methods: Based on unsupervised clustering and the expression levels of ferroptosis genes, patients with cancer were divided into two clusters. The least absolute shrinkage and selection operator method Cox regression analysis was used to establish the survival-predictor model. Results: Based on the pan-cancer analysis, a 20 gene-based survival-predictor model for predicting survival rates was developed, which was validated in patients with hepatocellular carcinoma. Conclusion: The survival-predictor model accurately predicted the prognosis of patients with digestive tract tumors.

Directional phase-unwrapping algorithm and phase shift technique on hydrogel.

Refractive index microstructures, which can be written by multiphoton absorption with femtosecond lasers, have many applications. Here we present a directional phase-unwrapping algorithm with phase-shifting technique and apply it to the metrology of hydrogel microstructures. A staircase phase-unwrapping algorithm is demonstrated. This fast quality-guided path phase-unwrapping applies well to situations that are geometrically well defined and is quite tolerant of phase noise. To achieve precise very small phase shifts, we also present a slant angle technique on a DC servo stage along with phase shift measurement, allowing us to achieve 6.5 nm step sizes.

Derivation and validation of the ED-SAS score for very early prediction of mortality and morbidity with acute pancreatitis: a retrospective observational study.

BACKGROUND: Existing scoring systems to predict mortality in acute pancreatitis may not be directly applicable to the emergency department (ED). The objective of this study was to derive and validate the ED-SAS, a simple scoring score using variables readily available in the ED to predict mortality in patients with acute pancreatitis. METHODS: This retrospective observational study was performed based on patient data collected from electronic health records across 2 independent health systems; 1 was used for the derivation cohort and the other for the validation cohort. Adult patients who were eligible presented to the ED, required hospital admission, and had a confirmed diagnosis of acute pancreatitis. Patients with chronic or recurrent episodes of pancreatitis were excluded. The primary outcome was 30-day mortality. Analyses tested and derived candidate variables to establish a prediction score, which was subsequently applied to the validation cohort to assess odds ratios for the primary and secondary outcomes. RESULTS: The derivation cohort included 599 patients, and the validation cohort 2011 patients. Thirty-day mortality was 4.2 and 3.9%, respectively. From the derivation cohort, 3 variables were established for use in the predictive scoring score: ≥2 systemic inflammatory response syndrome (SIRS) criteria, age > 60 years, and SpO2 < 96%. Summing the presence or absence of each variable yielded an ED-SAS score ranging from 0 to 3. In the validation cohort, the odds of 30-day mortality increased with each subsequent ED-SAS point: 4.4 (95% CI 1.8-10.8) for 1 point, 12.0 (95% CI 4.9-29.4) for 2 points, and 41.7 (95% CI 15.8-110.1) for 3 points (c-statistic = 0.77). CONCLUSION: An ED-SAS score that incorporates SpO2, age, and SIRS measurements, all of which are available in the ED, provides a rapid method for predicting 30-day mortality in acute pancreatitis.

Are CAR-T therapies living up to their hype? A study using real-world data in two cohorts to determine how well they are actually working in practice compared with bone marrow transplants.

With the increasing use of new regulatory tools, like the Food and Drug Administration's breakthrough designation, there are increasing challenges for European health technology assessors (HTAs) to make an accurate assessment of the long-term value and performance of chimeric antigen receptor T-cell (CAR-T) therapies, particularly for orphan conditions, such as acute lymphoblastic leukaemia. The aim of this study was to demonstrate a novel methodology harnessing longitudinal real-world data, extracted from the electronic health records of a medical centre functioning as a clinical trial site, to develop an accurate analysis of the performance of CAR-T compared with the next-best treatment option, namely allogeneic haematopoietic cell transplant (HCT). The study population comprised 43 subjects in two cohorts: 29 who had undergone HCT treatment and 14 who had undergone CAR-T therapy. The 3-year relapse-free survival probability was 46% (95% CI: 08% to 79%) in the CAR-T cohort and 68% (95% CI: 46% to 83%) in the HCT cohort. To explain the lower RFS probability in the CAR-T cohort compared with the HCT cohort, the authors hypothesised that the CAR-T cohort had a far higher level of disease burden. This was validated by log-rank test analysis (p=0.0001) and confirmed in conversations with practitioners at the study site. The authors are aware that the small populations in this study will be seen as limiting the generalisability of the findings to some readers. However, in consultation with many European HTAs and regulators, there is broad agreement that this methodology warrants further investigation with a larger study.

GABAergic neurons in the insular cortex play an important role in cue-morphine reward memory reconsolidation.

AIMS: There have been recent reports that reconsolidation-based interventions attenuate drug reward memories in rodents. The insular cortex (IC) is an essential part of neural circuits that underlie cue-drug memory reconsolidation. GABAergic interneurons in the IC are a potent control on network excitability and play an important role in the inhibitory mediation of reward circuits. However, the function of GABAergic neurons in the IC for memory reconsolidation remains unclear; therefore, we conducted this study to clarify this. MAIN METHODS: We applied morphine-induced conditioned place preference (mCPP) paradigm and pharmacogenetic techniques to study the mediation effect of GABAergic neurons in the IC on mCPP reconsolidation. Moreover, we preliminarily explored the possible mechanisms of mediating GABAergic neurons in the IC involved in mCPP reconsolidation by assessing Arc and Erg-1 protein levels in the IC. KEY FINDINGS: We found that post-retrieval immediate activation of GABAergic neurons in the IC impaired mCPP reconsolidation. In addition, this effect was not reversed by a priming morphine injection. Further, post-retrieval inhibition and non-retrieval excitation of GABAergic neurons in the IC had no effect on mCPP. SIGNIFICANCE: Taken together, our findings suggest that GABAergic neurons in the IC are closely involved in mCPP reconsolidation. Specifically, their excitation could eliminate established mCPP and prevent the relapse risk by disruption of the reconsolidation. The underlying molecular biological mechanisms could involve reduced Arc and Erg-1 levels.