Infralimbic YTHDF1 is necessary for the beneficial effects of acute mild exercise on auditory fear extinction retention.

Exposure therapy is the most effective approach of behavioral therapy for anxiety and post-traumatic stress disorder (PTSD). But fear is easy to reappear even after successful extinction. So, identifying novel strategies for augmenting exposure therapy is rather important. It was reported that exercise had beneficial effects on cognitive and memory deficits. However, whether exercise could affect fear memory, especially for fear extinction remained elusive. Here, our results showed that exposure to acute mild exercise 1 or 2 h before extinction training can augment recent fear extinction retention and 2 h for the remote fear extinction retention. These beneficial effects could be attributed to increased YTHDF1 expression in medial prefrontal cortex (mPFC). Furthermore, by using an AAV-shRNA-based approach to silence YTHDF1 expression via stereotactic injection in prelimbic cortex (PL) or infralimbic cortex (IL), respectively, we demonstrated that silence YTHDF1 in IL, but not in PL, blunted augmentation of exposure therapy induced by acute mild exercise and accompanied with decreased NR2B and GluR1 expression. Moreover, YTHDF1 modulated dendritic spines remodeling of pyramidal neuron in IL. Collectively, our findings suggested that acute mild exercise acted as an effective strategy in augmenting exposure therapy with possible implications for understanding new treatment underlying PTSD.

Comprehensive Evolution and Expression anaLysis of PHOSPHATE 1 Gene Family in Allotetraploid Brassica napus and Its Diploid Ancestors.

The members of PHOSPHATE 1 (PHO1) family play important roles in plant phosphate (Pi) transport and adaptation to Pi deficiency. The functions of PHO1 family proteins have been reported in several plant species, with the exception of Brassica species. Here, we identified 23, 23, and 44 putative PHO1 family genes in Brassica rapa, Brassica oleracea, and Brassica napus by whole genome analysis, respectively. The phylogenetic analysis divided PHO1 family proteins into eight groups, which represented the orthologous relationships among PHO1 members. The gene structure and the conserved motif analysis indicated that the most PHO1 family genes had similar gene structures and the PHO1 proteins shared mutual conserved motifs. The chromosome distribution analysis showed that the majority of BnPHO1 family genes distributed analogously at chromosomes with BrPHO1 and BoPHO1 family genes. The data showed that PHO1 family genes were highly conserved during evolution from diploid to tetraploid. Furthermore, the expression analysis showed that PHO1 family genes had different expression patterns in plant tissues, suggesting the diversity of gene functions in Brassica species. Meanwhile, the expression analysis also revealed that some PHO1 family genes were significantly responsive to Pi deficiency, suggesting that PHO1 family genes play critical roles in Pi uptake and homeostasis under low Pi stress. Altogether, the characteristics of PHO1 family genes provide a reliable groundwork for further dissecting their functions in Brassica species.

Genetic association study of intron variants in the forkhead box protein P3 gene in Chinese patients diagnosed with cervical cancer.

The aim of this study was to investigate the effects of forkhead box protein P3 (FOXP3) intron single nucleotide variants (SNVs) in high-risk human papilloma virus (HR-HPV) infection and cervical cancer (CC) malignant lesions. We performed FOXP3 genotyping in 350 patients with CC and 350 healthy controls using the ImLDR multiple single nucleotide polymorphism genotyping technology. The heterozygous mutation TC in rs2294021 decreased the risk of HR-HPV infection and CC malignant lesions (TC vs. TT: OR = 0.71, 95% CI = 0.51-0.99); the dominant model TC+CC and allele C in rs2294021 decreased the risk of CC malignant lesions (TC+CC vs. TT: OR = 0.69, 95% CI = 0.50-0.95; C vs. T: OR = 0.78, 95% CI = 0.63-0.97). The heterozygous mutation GA, dominant model GA+AA and allele A in rs3761549 also decreased the risk of HR-HPV infection and CC malignant lesions (GA vs. GG: OR = 0.70, 95% CI = 0.51-0.96; GA+AA vs. GG: OR = 0.69, 95% CI = 0.51-0.94; A vs. G: OR = 0.75, 95% CI = 0.58-0.96). Patients with CC and HR-HPV infection carrying rs2294021 TC and rs3761549 GA had lower expression of FOXP3 protein. Haplotype analysis revealed that T-C-A decreased the risk of HR-HPV infection. Furthermore, we found a significant association between immune cells infiltration and prognosis in patients with CC. Our findings demonstrated that rs2294021 and rs3761549 variants may protect against HR-HPV and CC malignant lesions by downregulating FOXP3 and that FOXP3 was associated with immune cells infiltration, which affected the prognosis of CC.

Concise Synthesis of 1-Thioalkyl Glycoside Donors by Reaction of Per-O-acetylated Sugars with Sodium Alkanethiolates under Solvent-Free Conditions.

A relatively green method for synthesizing 1-thioalkyl glycosides has been developed, where sodium alkanethiolates were used to react with per-O-acetylated sugars instead of odorous alkyl mercaptans in the presence of BF3·Et2O without the use of solvents under mild conditions. Furthermore, we found that 1,2-trans-ß-thioglycosides can be converted into corresponding 1,2-cis-α-thioglycosides in the presence of trifluoromethanesulfonic acid in nonpolar solvents under mild conditions. This provides a simple and efficient new approach for synthesizing challenging 1,2-cis-α-thioglycosides.

Efficient Synthesis of 2-OH Thioglycosides from Glycals Based on the Reduction of Aryl Disulfides by NaBH4.

An improved method to efficiently synthesize 2-OH thioaryl glycosides starting from corresponding per-protected glycals was developed, where 1,2-anhydro sugars were prepared by the oxidation of glycals with oxone, followed by reaction of crude crystalline 1,2-anhydro sugars with NaBH4 and aryl disulfides. This method has been further used in a one-pot reaction to synthesize glycosyl donors having both "armed" and "NGP (neighboring group participation)" effects.

The role of fixation disengagement and oculomotor preparation in gap saccade task is gap-duration dependent.

The influence of internal brain state on behavioral performance is well illustrated by the gap saccade task, in which saccades might be initiated with short latency (express saccade) or with long latency (regular saccade) even though the external visual condition is identical. Accumulated evidence has demonstrated that the internal brain state is different before the initiation of an express saccade than a regular saccade. However, the reported origin of the fluctuation of internal brain state is disputed among previous studies, e.g., the fixation disengagement theory versus the oculomotor preparation theory. The present study examined these two theories by analyzing the rate and direction of fixational saccades, i.e., small amplitude saccades during fixation, because they could be modulated by the internal brain state. Since fixation disengagement is not spatially tuned, it might affect the rate but not the direction of fixational saccades. In contrast, oculomotor preparation can contain spatial information for the upcoming saccade and thus affect fixational saccade direction. We found that the different spatiotemporal characteristics of fixational saccades among tasks with different gap durations reveal diverse driving force to change the internal brain state. Under short gap duration (100 ms), fixation disengagement plays a primary role in switching internal brain states. Conversely, oculomotor preparation plays a primary role under medium (200 ms) and long (400 ms) gap durations. These results suggest that both fixation disengagement and oculomotor preparation can change the internal brain state, but their relative contributions are gap-duration dependent.NEW & NOTEWORTHY While performing the gap saccade task, the role of fixation disengagement and oculomotor preparation in modulating the internal brain state is gap-duration dependent. Fixation disengagement plays a primary role when gap duration is shorter (100 ms), whereas oculomotor preparation plays a primary role when gap duration is longer (200 ms and 400 ms).

Helicobacter pylori promote inflammation and host defense through the cagA-dependent activation of mTORC1.

Mechanistic target of rapamycin complex 1 (mTORC1) functions as regulating different cellular processes, including cell growth, proliferation, motility, survival, metabolism, autophagy, and protein transcription. Recently, it also found to be associated with many infections and inflammatory diseases, playing complex roles in pathogens growth and inflammation regulation. However, the regulation mechanism of mTORC1 in gastric epithelial cells and its role in Helicobacter pylori (H. pylori) infection and related gastritis remain unclear. Here, we identified that the phosphorylation of mechanistic target of rapamycin (mTOR) and the expression of DEP domain-containing mTOR-interacting protein (DEPTOR) was increased in gastric mucosa of H. pylori-infected patients and mice, as well as in H. pylori-infected gastric epithelial cells, which were largely depended on H. pylori cagA. The expression of DEPTOR was regulated via mTORC1, but, in turn, inhibited mTORC1. Knockdown mTOR significantly decreased expression and secretion of cytokines tumor necrosis factor-α, interleukin-1ß, and interleukin-6, chemokines CCL7 and CXCL16, and antimicrobial peptide LL37 in vitro, while knockdown DEPTOR had the opposite effect. Similar observations were made using mTOR knockout (KO) mice in vivo, moreover. The gastric inflammation was attenuated, while the bacterial burden was increased in mTOR KO mice during H. pylori infection. These findings supported H. pylori promote gastritis and inhibit bacterial colonization through the cagA-dependent activation of mTORC1.

The ARF7 and ARF19 Transcription Factors Positively Regulate PHOSPHATE STARVATION RESPONSE1 in Arabidopsis Roots.

PHOSPHATE STARVATION RESPONSE1 (PHR1) is a key regulatory component of the response to phosphate (Pi) starvation. However, the regulation of PHR1 in this response remains poorly understood. Here, we report that PHR1 is a target of the transcription factors AUXIN RESPONSE FACTOR7 (ARF7) and ARF19 and is positively regulated by auxin signaling in Arabidopsis (Arabidopsis thaliana) roots. PHR1 expression was induced by exogenous auxin and suppressed by auxin transport inhibitors in Arabidopsis roots. In the PHR1 promoter, three auxin-response elements, which are bound directly by ARF7 and ARF19, were shown to be essential for PHR1 expression. The arf7, arf19, and arf7 arf19 mutants showed down-regulated expression of PHR1 and downstream Pi starvation-induced genes in roots; they also exhibited defective Pi uptake in roots and overaccumulation of anthocyanin in shoots. The induction of lateral root formation in response to low Pi and to exogenous auxin was decreased in the phr1 mutant, whereas the expression of LATERAL ORGAN BOUNDARIES-DOMAIN16 (LBD16) and LBD29 was not changed significantly. PHR1 acted independently of LBD16 and LBD29 in the regulation of lateral root formation in response to low Pi. Under low-Pi conditions, lateral root impairment in the arf7 arf19 mutant was partially rescued by constitutive expression of PHR1, demonstrating that reduced PHR1 expression contributed to the arf7 arf19 phenotype. In addition to PHR1, other genes encoding MYB-CC members also were targets of ARF7 and ARF19. Our work thus reveals a mechanism coordinating auxin signaling and the PHR1 regulon in Arabidopsis responses to Pi deficiency.

Two subdivisions of macaque LIP process visual-oculomotor information differently.

Although the cerebral cortex is thought to be composed of functionally distinct areas, the actual parcellation of area and assignment of function are still highly controversial. An example is the much-studied lateral intraparietal cortex (LIP). Despite the general agreement that LIP plays an important role in visual-oculomotor transformation, it remains unclear whether the area is primary sensory- or motor-related (the attention-intention debate). Although LIP has been considered as a functionally unitary area, its dorsal (LIPd) and ventral (LIPv) parts differ in local morphology and long-distance connectivity. In particular, LIPv has much stronger connections with two oculomotor centers, the frontal eye field and the deep layers of the superior colliculus, than does LIPd. Such anatomical distinctions imply that compared with LIPd, LIPv might be more involved in oculomotor processing. We tested this hypothesis physiologically with a memory saccade task and a gap saccade task. We found that LIP neurons with persistent memory activities in memory saccade are primarily provoked either by visual stimulation (vision-related) or by both visual and saccadic events (vision-saccade-related) in gap saccade. The distribution changes from predominantly vision-related to predominantly vision-saccade-related as the recording depth increases along the dorsal-ventral dimension. Consistently, the simultaneously recorded local field potential also changes from visual evoked to saccade evoked. Finally, local injection of muscimol (GABA agonist) in LIPv, but not in LIPd, dramatically decreases the proportion of express saccades. With these results, we conclude that LIPd and LIPv are more involved in visual and visual-saccadic processing, respectively.

ING5 inhibits cell proliferation and invasion in esophageal squamous cell carcinoma through regulation of the Akt/NF-κB/MMP-9 signaling pathway.

The inhibitor of growth 5 (ING5) is a new candidate tumor suppressor gene (TSG) of the ING family. So far, there have been many reports about its functions related to cancer development. However, the biological roles of ING5 in esophageal squamous cell carcinoma (ESCC) remain unclear. In the present study, we demonstrated that ING5 was lowly expressed in ESCC tissues and cell lines. Overexpression of ING5 inhibited ESCC cell proliferation and invasion in vitro as well as suppressed tumor growth and metastasis in vivo. We also found that overexpression of ING5 significantly decreased the levels of p-AKT, NF-κB and MMP-9 in ECA109 cells. Taken together, these findings demonstrated that ING5 inhibited cell proliferation and invasion in ESCC through regulation of the Akt/NF-κB/MMP-9 signaling pathway. Thus, ING5 might be considered a promising target for ESCC treatment.

Stochastic Oscillation in Self-Organized Critical States of Small Systems: Sensitive Resting State in Neural Systems.

Self-organized critical states (SOCs) and stochastic oscillations (SOs) are simultaneously observed in neural systems, which appears to be theoretically contradictory since SOCs are characterized by scale-free avalanche sizes but oscillations indicate typical scales. Here, we show that SOs can emerge in SOCs of small size systems due to temporal correlation between large avalanches at the finite-size cutoff, resulting from the accumulation-release process in SOCs. In contrast, the critical branching process without accumulation-release dynamics cannot exhibit oscillations. The reconciliation of SOCs and SOs is demonstrated both in the sandpile model and robustly in biologically plausible neuronal networks. The oscillations can be suppressed if external inputs eliminate the prominent slow accumulation process, providing a potential explanation of the widely studied Berger effect or event-related desynchronization in neural response. The features of neural oscillations and suppression are confirmed during task processing in monkey eye-movement experiments. Our results suggest that finite-size, columnar neural circuits may play an important role in generating neural oscillations around the critical states, potentially enabling functional advantages of both SOCs and oscillations for sensitive response to transient stimuli.

Erratum to "Bladder-embedded ectopic intrauterine device with calculus".

[This corrects the article DOI: 10.1515/med-2020-0173.].

Subthalamic nucleus input-output dynamics are correlated with Parkinson's burden and treatment efficacy.

The subthalamic nucleus (STN) is pivotal in basal ganglia function in health and disease. Micro-electrode recordings of >25,000 recording sites from 146 Parkinson's patients undergoing deep brain stimulation (DBS) allowed differentiation between subthalamic input, represented by local field potential (LFP), and output, reflected in spike discharge rate (SPK). As with many natural systems, STN neuronal activity exhibits power-law dynamics characterized by the exponent α. We, therefore, dissected STN data into aperiodic and periodic components using the Fitting Oscillations & One Over F (FOOOF) tool. STN LFP showed significantly higher aperiodic exponents than SPK. Additionally, SPK beta oscillations demonstrated a downward frequency shift compared to LFP. Finally, the STN aperiodic and spiking parameters explained a significant fraction of the variance of the burden and treatment efficacy of Parkinson's disease. The unique STN input-output dynamics may clarify its role in Parkinson's physiology and can be utilized in closed-loop DBS therapy.

[Source Apportionment and Response to Landscape Pattern of Health Risk of Cultivated Soil Heavy Metals].

Heavy metal pollution mainly caused by human activities is becoming increasingly prominent and threatening human health and ecosystem safety in soil, which is a non-renewable natural resource that humans rely on for survival and development. Assessment and analysis of soil heavy metal health risk is significant for protecting human health, preventing soil pollution, and maintaining ecosystem security. Based on the investigation of heavy metals, including Cr, Pb, Cd, As, and Hg, in cultivated soil in Liuhe District, the health risk assessment model was used to identify the health risk characteristics of heavy metals, and the spatial distribution, main sources, and responses to landscape patterns were explored by using inverse distance weight interpolation, positive definite matrix factorization, landscape pattern index, and redundancy analysis. The results showed that the coefficients of variation corresponding to Cr, Pb, Cd, As, and Hg in the study area were 0.19, 0.36, 0.23, 0.52, and 1.16, respectively, all of which belonged to moderate or high variability, indicating that they had high spatial heterogeneity and were susceptible to human factors. Cr, Pb, and As were the main health risk characteristic factors in the study area, with the carcinogenic risks to children ranging from 13.307×10-6 to 38.400×10-6, 0.839×10-6 to 3.250×10-6, and 4.548×10-6 to 16.680×10-6, respectively, which were higher than those in adults. Agricultural production activities, industrial production, and transportation activities were the main sources of heavy metals, with carcinogenic risks to children of 17.946×10-6 and 12.941×10-6, respectively. Furthermore, high-risk areas caused by agricultural production activities were mainly concentrated in the northern area of Liuhe District and showed an increasing trend from south to north and from the center to the periphery. The surrounding areas caused by industrial production activities and transportation were mainly concentrated in the chemical industry park and economic development zone of Liuhe District and showed a spatial agglomeration feature of decreasing from south to north and from the core to the periphery. The cumulative explanatory value of the landscape pattern index for the comprehensive carcinogenic risk to children was 0.463, and patch density, patch proportion in landscape area, patch aggregation degree, and maximum patch index had significant effects on the comprehensive carcinogenic risk in children, and the corresponding explanatory values were 0.422, 0.274, 0.351, and 0.232, respectively. This study had important theoretical and practical significance for expanding the perspective of environmental health research, promoting the transformation of soil heavy metal management methods and safeguarding regional population health.

Chinese formula Guben-Jiannao Ye alleviates the dysfunction of circadian and sleep rhythms in APP/PS1 mice implicated in activation of the PI3K/AKT/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The Chinese formula Guben-Jiannao Ye (GBJNY) formula has a long history of usage in traditional Chinese medicine (TCM) for the treatment of learning and memory disorders as well as senile insomnia. This formulation is derived from Sun Simiao's five tonic pills. Furthermore, modern pharmacological investigations have revealed its ability to improve cognitive impairment and ameliorate sleep-wake circadian rhythm disorders. However, the precise mechanism underlying its efficacy remains elusive. AIM OF THE STUDY: The current research explored the modulatory effects and possible mechanisms of GBJNY in circadian rhythm sleep-wake disorders and cognitive dysfunction in Alzheimer's disease using transcriptome sequencing and experimental validation. MATERIALS AND METHODS: The LC-MS/MS tandem technology was utilized to qualitatively discern the active components present in GBJNY. The APP/PS1 mice received continuous treatment with GBJNY or Melatonin for 3 months. The learning and memory abilities of mice were assessed utilizing the Morris water maze (MWM) test, while sleep changes were studied utilizing the electroencephalogram (EEG) and electromyogram (EMG). Concurrently, mice's hippocampus clock gene rhythmicity was investigated. Subsequently, we employed HE staining, Golgi staining, and immunofluorescence to observe GBJNY's impact on synaptic damage and neuronal loss. We performed high-throughput sequencing to analyze the mRNA expression profiles of mice, aiming to identify differentially expressed genes (DEGs). Subsequently, we conducted GO and KEGG enrichment analyses to explore associated signaling pathways. Furthermore, we evaluated the expression levels of proteins involved in the PI3K/AKT/mTOR pathway and Aß deposition in the hippocampus of mice. Through this comprehensive approach, we sought to elucidate and validate the potential mechanisms of action of GBJNY in APP/PS1 mice. RESULTS: Results showed 216 DEGs. Following this, we conducted GO enrichment and KEGG pathway analyses to delve deeper into the distinctions and fundamental functions of the mRNA target genes. The enrichment analysis underscored the prominence of the PI3K/Akt/mTOR signaling pathway as the most pivotal among them. Through in vivo experiments, it was further demonstrated that the administration of GBJNY enhanced memory and learning capacities in APP/PS1 mice. Additionally, GBJNY treatment resulted in alterations in the sleep-wake circadian rhythm, characterized by reduced wakefulness and an increase in non-rapid eye movement (NREM) sleep. Moreover, alterations in the peak expression of Per1, Per2, Clock, Cry1, Cry2, and Bmal1 mRNA were noted in the hippocampus of treated mice. Particularly noteworthy were the observed reductions in amyloid-beta (Aß) deposition within the hippocampus, improvements in neuronal synaptic integrity, and upregulation of mTOR, Akt, and PI3K protein expression in the hippocampal region. These findings underscore the critical involvement of the PI3K/Akt/mTOR signaling pathway in mitigating disturbances in sleep-wake circadian rhythms. CONCLUSIONS: GBJNY enhanced the cognitive performance of APP/PS1 mice and altered clock gene expression patterns, alleviating sleep-wake circadian rhythm disruptions. The fundamental mechanism appears to be linked to the PI3K/Akt/mTOR pathway regulation, offering a foundation for potential clinical applications.

Digital identification and adulteration analysis of Pulsatilla Radix and Pulsatilla Cernua based on "digital identity" and UHPLC-QTOF-MSE.

Under the background of digitalization of traditional Chinese medicine (TCM), to realize the quick identification and adulteration analysis of Pulsatilla Radix (PR), adhering to digital conviction, this study conducted UHPLC-QTOF-MSE analysis on PR and its adulterant-Pulsatilla Cernua (PC) from different batches and based on digital conversion, the shared ions were extracted from different batches of PR and PC as their "ions representation", respectively. Further, the data set of unique ions of PR relative to PC and PC relative to PR were screened out as the "digital identities" of PR and PC respectively. Further, above the "digital identities" of PR and PC were used as the benchmarks for matching and identifying to feedback give a matching credibility (MC). The results showed that based on the "digital identities" of PR and PC, the digital identification of two herbal samples can be realized efficiently and accurately at the individual level with the MC≥70.00 %, even if 5 % of PC in the mixed samples can still be identified efficiently and accurately. The study is of great practical significance for improving the identification efficiency of PR and PC, cracking down on adulterated and counterfeit drugs, and strengthening the quality control of PR. In addition, it has important reference significance for developing non-targeted digital identification of herbal medicines at the individual level based on UHPLC-QTOF-MSE and the "digital identity", which was beneficial to the construction of digital Chinese medicine and digital quality control.

Microglial activation in the medial prefrontal cortex after remote fear recall participates in the regulation of auditory fear extinction.

Excessive or inappropriate fear responses can lead to anxiety-related disorders, such as post-traumatic stress disorder (PTSD). Studies have shown that microglial activation occurs after fear conditioning and that microglial inhibition impacts fear memory. However, the role of microglia in fear memory recall remains unclear. In this study, we investigated the activated profiles of microglia after the recall of remote-cued fear memory and the role of activated microglia in the extinction of remote-cued fear in adult male C57BL/6 mice. The results revealed that the expression of the microglia marker Iba1 increased in the medial prefrontal cortex (mPFC) at 10 min and 1 h following remote-cued fear recall, which was accompanied by amoeboid morphology. Inhibiting microglial activation through PLX3397 treatment before remote fear recall did not affect recall, reconsolidation, or regular extinction but facilitated recall-extinction and mitigated spontaneous recovery. Moreover, our results demonstrated reduced co-expression of Iba1 and postsynaptic density protein 95 (PSD95) in the mPFC, along with decreases in the p-PI3K/PI3K ratio, p-Akt/Akt ratio, and KLF4 expression after PLX3397 treatment. Our results suggest that microglial activation after remote fear recall impedes fear extinction through the pruning of synapses in the mPFC, accompanied by alterations in the expression of the PI3K/AKT/KLF4 pathway. This finding can help elucidate the mechanism involved in remote fear extinction, contributing to the theoretical foundation for the intervention and treatment of PTSD.

A severe case of iatrogenic botulism associated with COVID-19 infection.

Background: The botulinum toxin is an extremely potent substance that impacts the nervous system. There has been a rise in cases of medical poisoning associated with it, particularly in the field of plastic and aesthetic procedures, in recent years. Case description: A 51-year-old woman underwent a facial wrinkle reduction procedure with an unauthorized injection of 100 U of botulinum toxin at an unlicensed medical facility six days prior to hospitalization. Over time, her toxicity symptoms intensified, impacting her respiratory muscles, and she did not receive antitoxin treatment. She was concurrently diagnosed with a COVID-19 infection during this period. Nonetheless, she experienced a full recovery 86 days after the injection. Conclusion: Currently, there is no effective antidote for botulism. Nevertheless, the timely administration of antitoxin can contribute to reducing the duration of the illness, alleviating symptoms, and preventing its recurrence. It is essential to recognize that individual responses may vary, and in this instance, the absence of antitoxin treatment did not significantly prolong the course of the disease. Accurate diagnosis of medical poisoning can be based on injection history and clinical symptoms. Early indications like fatigue and dry mouth warrant particular attention, emphasizing the importance of immediate medical intervention. To address emergencies, the Center for Disease Control (CDC) should maintain an accessible supply of antitoxin. Patients with severe poisoning should be hospitalized until their respiratory muscle strength is fully restored.

CK2 negatively regulates the extinction of remote fear memory.

Cognitive behavioral therapy, rooted in exposure therapy, is currently the primary approach employed in the treatment of anxiety-related conditions, including post-traumatic stress disorder (PTSD). In laboratory settings, fear extinction in animals is a commonly employed technique to investigate exposure therapy; however, the precise mechanisms underlying fear extinction remain elusive. Casein kinase 2 (CK2), which regulates neuroplasticity via phosphorylation of its substrates, has a significant influence in various neurological disorders, such as Alzheimer's disease and Parkinson's disease, as well as in the process of learning and memory. In this study, we adopted a classical Pavlovian fear conditioning model to investigate the involvement of CK2 in remote fear memory extinction and its underlying mechanisms. The results indicated that the activity of CK2 in the medial prefrontal cortex (mPFC) of mice was significantly upregulated after extinction training of remote cued fear memory. Notably, administration of the CK2 inhibitor CX-4945 prior to extinction training facilitated the extinction of remote fear memory. In addition, CX-4945 significantly upregulated the expression of p-ERK1/2 and p-CREB in the mPFC. Our results suggest that CK2 negatively regulates remote fear memory extinction, at least in part, by inhibiting the ERK-CREB pathway. These findings contribute to our understanding of the underlying mechanisms of remote cued fear extinction, thereby offering a theoretical foundation and identifying potential targets for the intervention and treatment of PTSD.

Degradation of perineuronal nets in the medial prefrontal cortex promotes extinction and reduces reinstatement of methamphetamine-induced conditioned place preference in female mice.

The high rate of relapse to compulsive methamphetamine (MA)-taking and seeking behaviors after abstinence constitutes a major obstacle to the treatment of MA addiction. Perineuronal nets (PNNs), essential components of the extracellular matrix, play a critical role in synaptic function, learning, and memory. Abnormalities in PNNs have been closely linked to a series of neurological diseases, such as addiction. However, the exact role of PNNs in MA-induced related behaviors remains elusive. Here, we established a MA-induced conditioned place preference (CPP) paradigm in female mice and found that the number and average optical density of PNNs increased significantly in the medial prefrontal cortex (mPFC) of mice during the acquisition, extinction, and reinstatement stages of CPP. Notably, the removal of PNNs in the mPFC via chondroitinase ABC (ChABC) before extinction training not only facilitated the extinction of MA-induced CPP and attenuated the relapse of extinguished MA preference but also significantly reduced the activation of c-Fos in the mPFC. Similarly, the ablation of PNNs in the mPFC before reinstatement markedly lessened the reinstatement of MA-induced CPP, which was accompanied by the decreased expression of c-Fos in the mPFC. Collectively, our results provide more evidence for the implication of degradation of PNNs in facilitating extinction and preventing relapse of MA-induced CPP, which indicate that targeting PNNs may be an effective therapeutic option for MA-induced CPP memories.