Enhanced patient-based real-time quality control using the graph-based anomaly detection.

OBJECTIVES: Patient-based real-time quality control (PBRTQC) is an alternative tool for laboratories that has gained increasing attention. Despite the progress made by using various algorithms, the problems of data volume imbalance between in-control and out-of-control results, as well as the issue of variation remain challenges. We propose a novel integrated framework using anomaly detection and graph neural network, combining clinical variables and statistical algorithms, to improve the error detection performance of patient-based quality control. METHODS: The testing results of three representative analytes (sodium, potassium, and calcium) and eight independent variables of patients (test date, time, gender, age, department, patient type, and reference interval limits) were collected. Graph-based anomaly detection network was modeled and used to generate control limits. Proportional and random errors were simulated for performance evaluation. Five mainstream PBRTQC statistical algorithms were chosen for comparison. RESULTS: The framework of a patient-based graph anomaly detection network for real-time quality control (PGADQC) was established and proven feasible for error detection. Compared with classic PBRTQC, the PGADQC showed a more balanced performance for both positive and negative biases. For different analytes, the average number of patient samples until error detection (ANPed) of PGADQC decreased variably, and reductions could reach up to approximately 95 % at a small bias of 0.02 taking calcium as an example. CONCLUSIONS: The PGADQC is an effective framework for patient-based quality control, integrating statistical and artificial intelligence algorithms. It improves error detection in a data-driven fashion and provides a new approach for PBRTQC from the data science perspective.

Roles of lncLingo2 and its derived miR-876-5p in the acquisition of opioid reinforcement.

Recent studies found that non-coding RNAs (ncRNAs) played crucial roles in drug addiction through epigenetic regulation of gene expression and underlying drug-induced neuroadaptations. In this study, we characterized lncRNA transcriptome profiles in the nucleus accumbens (NAc) of mice exhibiting morphine-conditioned place preference (CPP) and explored the prospective roles of novel differentially expressed lncRNA, lncLingo2 and its derived miR-876-5p in the acquisition of opioids-associated behaviours. We found that the lncLingo2 was downregulated within the NAc core (NAcC) but not in the NAc shell (NAcS). This downregulation was found to be associated with the development of morphine CPP and heroin intravenous self-administration (IVSA). As Mfold software revealed that the secondary structures of lncLingo2 contained the sequence of pre-miR-876, transfection of LV-lncLingo2 into HEK293 cells significantly upregulated miR-876 expression and the changes of mature miR-876 are positively correlated with lncLingo2 expression in NAcC of morphine CPP trained mice. Delivering miR-876-5p mimics into NAcC also inhibited the acquisition of morphine CPP. Furthermore, bioinformatics analysis and dual-luciferase assay confirmed that miR-876-5p binds to its target gene, Kcnn3, selectively and regulates morphine CPP training-induced alteration of Kcnn3 expression. Lastly, the electrophysiological analysis indicated that the currents of small conductance calcium-activated potassium (SK) channel was increased, which led to low neuronal excitability in NAcC after CPP training, and these changes were reversed by lncLingo2 overexpression. Collectively, lncLingo2 may function as a precursor of miR-876-5p in NAcC, hence modulating the development of opioid-associated behaviours in mice, which may serve as an underlying biomarker and therapeutic target of opioid addiction.

High-performance diode-end-pumped Nd:YLF laser operating at 1314†nm.

A stable, efficient, and powerful 1314 nm Nd:YLF laser inband-pumped by a wavelength-locked narrowband 880 nm laser diode is demonstrated. The influence of mode-to-pump ratio on the performance of the diode-end-pumped Nd:YLF laser has been systematically investigated by taking into account the thermal effect and the energy transfer upconversion effect. For the optimum mode-to-pump ratio of 0.84, the maximum continuous wave output power of 21.9 W was extracted under the pump power of 70 W, which corresponded to the optical power efficiency of 31.3% and the beam quality of M2 ≈ 1.6. The resultant output power stability was determined to be 0.059% (RMS) within 1 h. In addition, by increasing the mode-to-pump ratio to 1.0, the near-diffraction-limited beam (M2 ≈ 1.3) was achieved with the output power of 17.0 W and the optical power efficiency of 24.3%.

Nanosecond pulsed single longitudinal mode diamond Raman laser in the 1.6†µm spectral region.

We demonstrate the first nanosecond pulsed single longitudinal mode (SLM) intracavity-pumped diamond Raman laser, to the best of our knowledge. The eye-safe coherent source at 1634 nm, which was converted from the actively Q-switched 1342 nm Nd:YVO4 laser, yielded 4.35 W of multimode average output power with a pulse duration of 6 ns and peak power of 29 kW. By exploiting the spatial hole burning free gain mechanism in the Raman media, stable SLM operation was observed at low output power (0.46 W) for the free-running case. Furthermore, by incorporating an etalon in the fundamental standing-wave cavity, the spectral linewidth of the fundamental field was suppressed substantially below the diamond Raman gain linewidth and slightly less than the free spectral range of the mm-scale Raman resonator. Thereby, a much higher SLM output power of 1.63 W was obtained with a pulse duration of ∼9 ns and a spectral linewidth of ∼77 MHz.

Comparison of cracking activity of the core-shell composite MCM-41/HY & MCM-48/HY catalysts in the synthesis of organic liquid fuel from Mahua oil.

A synergistic catalyst was architectured using the hydrothermal crystallization method. Mesoporous material with pore diameter less than 20 nm was grown on the microporous Zeolite HY. The catalysts were characterized by XRD, ICP-OES, BET, TPD, SEM and TEM techniques. The SEM picture portrayed excellent core - shell morphology and TEM analysis corresponded to the XRD reports. Mahua oil was cracked in a pilot scale reactor over the synthesized catalysts at an optimized reaction condition (Temperature: 400 οC; WHSV: 4.6 h-1). The gaseous and liquid products of reaction were analyzed by Residual Gas analyzer and GCMS respectively. The NMR spectral analysis of fuel showed low traces of aromatics. The produced fuel was analyzed for its significant properties like calorific value, fire point, flash point and viscosity.

Microwave assisted biodiesel production from chicken feather meal oil using Bio-Nano Calcium oxide derived from chicken egg shell.

Environmental concerns have initiated the search for greener measures to mitigate pollution issues. Bio Nano CaO was synthesized by reducing CaO extracted from chicken egg shell using tea decoction. The synthesized material was characterized by physico-chemical techniques such as XRD, TGA, BET surface area analyser, TGA and SEM techniques. XRD studied confirmed the crystalline nature of material. The prepared material was found to be stable till 450 οC from TGA study. The SEM pictures displayed uniform and discrete particles which portrays the high probable sites that maximises the catalytic activity. The optimization of microwave assisted Biodiesel synthesis from chicken feather oil through Transesterification process using the bio-synthesized catalytic material was the main aim of the study. A 500 W microwave irradiation of Chicken feather meal oil using 8:1 Methanol:Oil input, 1% Bio Nano CaO concentration, 5 min of reaction time resulted in 95% conversion of chicken feather meal oil into chicken feather meal methyl esters. The Biodiesel was showed low viscosity (4.15 mm2/s), high heating value (50 MJ/kg), high flash point (153οC), reasonable pour point (12 οC) and good cetane number (50 min). The future works will be concentrated on the engine studies related to Torque, fuel consumption, emission data by using the synthesized Biodiesel.

Enhancing Handover for 5G mmWave Mobile Networks Using Jump Markov Linear System and Deep Reinforcement Learning.

The Fifth Generation (5G) mobile networks use millimeter waves (mmWaves) to offer gigabit data rates. However, unlike microwaves, mmWave links are prone to user and topographic dynamics. They easily get blocked and end up forming irregular cell patterns for 5G. This in turn causes too early, too late, or wrong handoffs (HOs). To mitigate HO challenges, sustain connectivity, and avert unnecessary HO, we propose an HO scheme based on a jump Markov linear system (JMLS) and deep reinforcement learning (DRL). JMLS is widely known to account for abrupt changes in system dynamics. DRL likewise emerges as an artificial intelligence technique for learning highly dimensional and time-varying behaviors. We combine the two techniques to account for time-varying, abrupt, and irregular changes in mmWave link behavior by predicting likely deterioration patterns of target links. The prediction is optimized by meta training techniques that also reduce training sample size. Thus, the JMLS-DRL platform formulates intelligent and versatile HO policies for 5G. When compared to a signal and interference noise ratio (SINR) and DRL-based HO scheme, our HO scheme becomes more reliable in selecting reliable target links. In particular, our proposed scheme is able to reduce wasteful HO to less than 5% within 200 training episodes compared to the DRL-based HO scheme that needs more than 200 training episodes to get to less than 5%. It supports longer dew time between HOs and high sum rates by ably averting unnecessary HOs with almost half the HOs compared to a DRL-based HO scheme.

Inhibitory Effect of CCK-8 on Methamphetamine-Induced Apoptosis.

OBJECTIVES: To investigate the inhibitory effect of cholecystokinin octapeptide (CCK-8) binding to cholecystokinin 2 receptor (CCK2R) on methamphetamine (METH)-induced neuronal apoptosis, and to explore the signal transduction mechanism of ß-arrestin 2 in CCK-8 inhibiting METH-induced neuronal apoptosis. METHODS: SH-SY5Y cell line was cultured, and HEK293-CCK1R and HEK293-CCK2R cell line were constructed by lentivirus transfection. Small interfering RNA (siRNA) was used to knockdown the expression of ß-arrestin 2. Annexin Ⅴ-FITC/PI staining and flow cytometry were used to detect the apoptotic rate of cells, and Western blotting was used to detect the expression of apoptosis-related proteins. RESULTS: The apoptosis of SH-SY5Y cells was induced by 1 mmol/L and 2 mmol/L METH treatment, the number of nuclear fragmentation and pyknotic cells was significantly increased, and the expression of apoptosis-related proteins Bax and cleaved caspase-3 were increased. CCK-8 pre-treatment at the dose of 0.1 mmol/L and 1 mmol/L significantly reversed METH-induced apoptosis in SH-SY5Y cells, and inhibited cell nuclear fragmentation, pyknosis and the changes of apoptosis-related proteins induced by METH. In lentivirus transfected HEK293-CCK1R and HEK293-CCK2R cells, the results revealed that CCK-8 had no significant effect on METH-induced changes of apoptosis-related proteins in HEK293-CCK1R cells, but it could inhibit the expression level of apoptosis-related proteins in HEK293-CCK2R cells induced by METH. The inhibitory effect of CCK-8 on METH-induced apoptosis was blocked by the knockdown of ß-arrestin 2 expression in SH-SY5Y cells. CONCLUSIONS: CCK-8 can bind to CCK2R and exert an inhibitory effect on METH-induced apoptosis by activating the ß-arrestin 2 signal.

Extracellular and Intracellular Polysaccharide Extracts of Trametes versicolor Improve Lipid Profiles Via Serum Regulation of Lipid-Regulating Enzymes in Hyperlipidemic Mice.

Trametes versicolor extracts have been shown to have health-promoting benefits in hypercholesterolemia, obesity, hepatic steatosis, and cardiovascular disease. However, hypolipidemic or the anti-hyperlipidemic effects of polysaccharide extracts of T. versicolor (PTVs) are not yet clear. In present work, the structural characterization of intracellular (IPTV) and the extracellular polysaccharide extracts of T. versicolor (EPTV) were partially clarified, and their effects on serum lipid metabolism and regulation of lipid-regulating enzymes in high-fat diet-induced hyperlipidemic mice were also investigated. Results indicated that IPTV and EPTV are α-pyran polysaccharide with an average molecular weight of 127 and 68.4 kDa, respectively, and were mainly composed of mannose, glucose and galactose. In vivo study, EPTV treatment (200 mg/kg/d) significantly decreased serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), and atherosclerosis index (AI) of hyperlipidemic mice by 20.97%, 57.85%, 27.72%, and 20.35%, respectively (P < 0.01), while IPTV treatment (100 mg/kg/d) showed a significant (P < 0.01) decrease in serum TC (17.05%), TG (43.80%), LDL-C (25.61%) levels, and AI value (13.32%). A significant increase in serum lipoprotein lipase (LPL) activity and decrease in protein expression of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) were observed following EPTV administration, while IPTV remarkably promoted LPL activity. These results suggest that IPTV and EPTV which improve serum lipid profiles in high-fat diet-induced hyperlipidemic mice via mechanisms regulated by serum LPL and hepatic HMGR have potential for further development as novel therapeutic dietary supplements for the prevention and treatment of hyperlipidemia.

Association of ATM and BMI-1 genetic variation with breast cancer risk in Han Chinese.

We tested the hypothesis that genetic variation in ATM and BMI-1 genes can alter the risk of breast cancer through genotyping 6 variants among 524 breast cancer cases and 518 cancer-free controls of Han nationality. This was an observational, hospital-based, case-control association study. Analyses of single variant, linkage, haplotype, interaction and nomogram were performed. Risk was expressed as odds ratio (OR) and 95% confidence interval (CI). All studied variants were in the Hardy-Weinberg equilibrium and were not linked. The mutant allele frequencies of rs1890637, rs3092856 and rs1801516 in ATM gene were significantly higher in cases than in controls (P = .005, <.001 and .001, respectively). Two variants, rs1042059 and rs201024480, in BMI-1 gene were low penetrant, with no detectable significance. After adjustment, rs189037 and rs1801516 were significantly associated with breast cancer under the additive model (OR: 1.37 and 1.52, 95% CI: 1.10-1.71 and 1.14-2.04, P: .005 and .005, respectively). In haplotype analysis, haplotypes A-C-G-G (in order of rs189037, rs3092856, rs1801516 and rs373759) and A-C-A-A in ATM gene were significantly associated with 1.98-fold and 6.04-fold increased risk of breast cancer (95% CI: 1.36-2.90 and 1.65-22.08, respectively). Nomogram analysis estimated that the cumulative proportion of 3 significant variants in ATM gene was about 12.5%. Our findings collectively indicated that ATM gene was a candidate gene in susceptibility to breast cancer in Han Chinese.

Genetic predisposition of six well-defined polymorphisms in HMGB1/RAGE pathway to breast cancer in a large Han Chinese population.

Breast cancer constitutes an enormous burden in China. A strong familial clustering of breast cancer suggests a genetic component in its carcinogenesis. To examine the genetic predisposition of high mobility group box-1/receptor for advanced glycation end products (HMGB1/RAGE) pathway to breast cancer, we genotyped six well-defined polymorphisms in this pathway among 524 breast cancer patients and 518 cancer-free controls from Heilongjiang province, China. There were no deviations from Hardy-Weinberg equilibrium for all polymorphisms. In single-locus analysis, the frequency of rs1800624 polymorphism mutant A allele in RAGE gene was significantly higher in patients than in controls (24.52% versus 19.50%, P = 0.006), with the carriers of rs1800624-A allele being 1.51 times more likely to develop breast cancer relative to those with rs1800624-GG genotype after adjustment (95% confidence interval or CI: 1.17-1.94, P = 0.001). In HMGB1 gene, haplotype analysis did not reveal any significance, while in RAGE gene, haplotypes C-T-A and C-A-G (alleles in order of rs1800625, rs18006024, rs2070600) were significantly associated with an increased risk of breast cancer (adjusted OR = 2.72 and 10.35; 95% CI: 1.20-6.18 and 1.58-67.80; P = 0.017 and 0.015 respectively). In further genetic score analysis, per unit and quartile increments of unfavourable alleles were significantly associated with an increased risk of breast cancer after adjustment (odds ratio or OR = 1.20 and 1.26; 95% CI: 1.09-1.32 and 1.12-1.42; P < 0.001 and <0.001 respectively). Our findings altogether demonstrate a significant association between RAGE gene rs1800624 polymorphism and breast cancer risk, and more importantly a cumulative impact of multiple risk associated polymorphisms in HMGB1/RAGE pathway on breast carcinogenesis.

Study on antibacterial molecular drugs in Eucalyptus granlla wood extractives by GC-MS.

Eucalyptus granlla, which was one of dominant plantations in south China, was deemed as the important wood bio resources. However, the small molecules of Eucalyptus granlla wood weren't effectively reused. Thus the molecules of wood extractives in Eucalyptus granlla were extracted and studied so as to further utilize the resources. The result suggested that the optimal extraction time of ethanol/methanol extraction, petroleum ether/acetic ether extraction, and benzene/alcohol extraction were 5h, 7h and 4h, respectively. The wood extractives included hexanedioic acid, bis (2-ethylhexyl) ester, 3,3,7,11-tetramethyltricyclo[5.4.0.0(4,11)] undecan-1-ol, squalene, etc. and wood extractives of Eucalyptus granlla was suitable for extraction of 1,5-hexadien-3-yne and squalene.

Separation characteristics of lignin from Eucalyptus camaldulensis lignin celluloses for biomedical cellulose.

The separation characteristics of Eucalyptus camaldulensis biomass cell wall were investigated and analyzed by FTIR, UV and XRD. The result showed that the crystallinity of untreated sample were lower than ones of treated samples at 10° C, 20° C and 30° C. Effect of temperature was very notable so as to use the lower temperature if cellulose would be kept natural structure during lignin separation from lignincellulose. Treatment time and temperature had a notably significant effect on SLR of E. camaldulensis lignin cellulose, and the SLR increased gradually with the temperature increment, and SLR were 73.35% at 10° C, 80.14% at 20° C, 83.73% at 30° C. The maximum of SLR increased with the rising of temperature 10° C, 20° C and 30° C. Consequently, the best separation conditions of lignin were 24h and 30° C. During hemicelluloses separation, the peak of C=O disappeared, and the peak of CO-OR, O-H and C-O abated, resulting that acetyl in hemicelluloses were mainly broken by the dehydration, heat decomposition reaction and mild thermal degradation. During lignin separation, the side chain and benzene ring of lignin of E. urophynis lignin cellulose reached the largest bond breaking characteristics under the temperature of 10° C at 7h, 20° C at 7h and 30° C at 24h.

Synergy of higher education resources and digital infrastructure construction in China: Regional differences, dynamic evolution and trend forecasting.

The deep integration of higher education with digital technology represents an inevitable trend, and evaluating the interplay between higher education resources (HER) and digital infrastructure construction (DIC) holds significant value for advancing the development of digital higher education and mitigating regional disparities in China. This study establishes two comprehensive evaluation frameworks for HER and DIC. Panel data from 31 provinces, spanning the period from 2011 to 2020, are utilized for analysis. The coupling coordination degree (CCD) model is employed in this work to evaluate the synergy between HER and DIC in China. Furthermore, we analyze the regional differences, spatial distribution, and trend evolution of this synergy. The study results revealed that there is an initial decrease followed by an increase in the synergy between HER and DIC, and the overall CCD is at a moderate coordination, with the mean CCD of the eastern region being significantly higher than that of the other three regions, and the inter-regional difference is the main source of regional disparity in this synergy. The current state of synergistic development reveals a slight inclination towards multi-polarization, although the disparity in regional development was decreasing. Additionally, there is an observed convergence in the coordinated development of HER and DIC, with spatial factors playing a significant role. These findings offer empirical support for efforts to enhance the integration of HER and DIC, reduce regional disparities in higher education, and foster sustainable development in China's higher education sector.

Elevated of NDUFA4L2 expression in colon adenocarcinoma is correlated with an unfavorable prognosis and increased immune cell infiltration.

Background: Colon adenocarcinoma (COAD) is a prevalent malignancy worldwide, yet, its underlying pathogenesis and genetic characteristics are still unclear. Previous studies have suggested that NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) may affect tumor progression across various cancers. However, this effect on COAD has rarely been reported. Thus, this study investigated NDUFA4L2's prognostic and diagnostic relevance and explored its potential connection with immune cell infiltration in COAD. Methods: To achieve this, RNA sequencing data from Cancer Genome Atlas (TCGA) was analyzed to assess NDUFA4L2's prognostic value in COAD, and factors relevant to the prognosis of COAD, including NDUFA4L2, were scrutinized using Kaplan-Meier analyses as well as univariate and multivariate Cox regression. A nomogram model was created to project prognosis based on the results of multivariate Cox analysis. Furthermore, gene set enrichment analysis (GSEA) was employed to pinpoint key NDUFA4L2-related pathways, and single-sample GSEA (ssGSEA) on TCGA data was employed to investigate the connections of NDUFA4L2 with cancer immune infiltrations. Results: Our findings revealed significant associations of high NDUFA4L2 expression with poor overall survival, progression-free interval, and disease-specific survival of COAD patients. GSEA indicated close links of NDUFA4L2 with several signaling pathways implicated in tumorigenesis, including extracellular matrix receptor interaction, the intestinal immune network for immunoglobulin A production, natural killer (NK) cell-mediated cytotoxicity, pathways in cancer, cell adhesion molecules, mitogen-activated protein kinase signaling pathway, Hedgehog signaling pathway, transforming growth factor beta signaling pathway, and chemokine signaling pathway. Additionally, ssGSEA identified a positive link between increased NDUFA4L2 expression and higher infiltration degree of various immune cells, such as immature dendritic cells, macrophages, NK cells and dendritic cells. Conclusions: Collectively, our findings demonstrate the association of increased NDUFA4L2 expression with adverse prognosis and heightened immune cell infiltration in COAD patients.

Next-Generation Patient-Based Real-Time Quality Control Models.

Patient-based real-time QC (PBRTQC) uses patient-derived data to assess assay performance. PBRTQC algorithms have advanced in parallel with developments in computer science and the increased availability of more powerful computers. The uptake of Artificial Intelligence in PBRTQC has been rapid, with many stated advantages over conventional approaches. However, until this review, there has been no critical comparison of these. The PBRTQC algorithms based on moving averages, regression-adjusted real-time QC, neural networks and anomaly detection are described and contrasted. As Artificial Intelligence tools become more available to laboratories, user-friendly and computationally efficient, the major disadvantages, such as complexity and the need for high computing resources, are reduced and become attractive to implement in PBRTQC applications.

Dopaminergic dominance in the ventral medial hypothalamus: A pivotal regulator for methamphetamine-induced pathological aggression.

Methamphetamine (METH) abuse is associated with a spectrum of behavioral consequences, among which heightened aggression presents a significant challenge. However, the causal role of METH's impact in aggression and its target circuit mechanisms remains largely unknown. We established an acute METH exposure-aggression mouse model to investigate the role of ventral tegmental area (VTA) dopaminergic neurons and ventral medial hypothalamus VMH glutamatergic neuron. Our findings revealed that METH-induced VTA dopamine excitability activates the ventromedial hypothalamus (VMH) glutamatergic neurons, contributing to pathological aggression. Notably, we uncovered a dopaminergic transmission within the VTA-VMH circuit that exclusively functioned under METH influence. This dopaminergic pathway emerged as a potential key player in enabling dopamine-related pathological aggression, with heightened dopaminergic excitability implicated in various psychiatric symptoms. Also, the modulatory function of this pathway opens new possibilities for targeted therapeutic strategies for intervention to improve treatment in METH abuse and may have broader implications for addressing pathological aggression syndromes.

Spatial spillover effect of Green Finance and Clean Energy on China's Provincial Green Economic Development.

Green finance is a new financing mode that pays attention to environmental benefits. Achieving a balance between the economy and the environment requires clean energy. For formulating policies to achieve sustainable development goals, it is very important to explore whether integrating green finance and clean energy is conducive to promoting green economic development (GED). This study applies a non-radial directional distance function (NDDF) to assess China's provincial GED using panel data from 2007 to 2020. It adopts the spatial Durbin model to empirically analyze the spatial spillover effects of green finance and clean energy on GED. The results indicate that: 1) The influence of green finance on GED shows a "U" curve relationship of first suppression and then rise. 2) A 1% increase in the synergy between green finance and clean energy yields a 0.1712% raise in the local GED and a 0.3482% boost to the surrounding area's GED through spatial spillovers. 3) The integration of green credit and clean energy has an apparent spatial spillover effect, and the interaction between green securities and clean energy can promote local GED. This study suggests that the government should accelerate and improve the development of a green financial market and establish a long-term linkage and co-ordination mechanism for the promotion of GED. It is crucial that financial institutions allocate more resources to clean energy development, and all regions will have to utilize the spatial spillover effect of clean energy to facilitate China's economic transformation and development in theory and practice.

The Role of circTmeff-1 in Morphine Addiction Memory of Mice.

In addition to the essential pharmacological effects of opioids, situational cues associated with drug addiction memory are key triggers for drug seeking. CircRNAs, an emerging hotspot regulator in crown genetics, play an important role in central nervous system-related diseases. However, the internal mediating mechanism of circRNAs in the field of drug reward and addiction memory remains unknown. Here, we trained mice on a conditional place preference (CPP) model and collected nucleus accumbens (NAc) tissues from day 1 (T0) and day 8 (T1) for high-throughput RNA sequencing. QRT-PCR analysis revealed that circTmeff-1 was highly expressed in the NAc core but not in the NAc shell, suggesting that it plays a role in addiction memory formation. Meanwhile, the down-regulation of circTmeff-1 by adeno-associated viruses in the NAc core or shell could inhibit the morphine CPP scores. Subsequently, the GO and KEGG analyses indicated that circTmeff-1 might regulate the addiction memory via the MAPK and AMPK pathways. These findings suggest that circTmeff-1 in NAc plays a crucial role in morphine-dependent memory formation.

Roles of nucleus accumbens shell small-conductance calcium-activated potassium channels in the conditioned fear freezing.

BACKGROUND: Posttraumatic stress disorder (PTSD), a psychiatric disorder caused by stressful events, is characterized by long-lasting fear memory. The nucleus accumbens shell (NAcS) is a key brain region that regulates fear-associated behavior. Small-conductance calcium-activated potassium channels (SK channels) play a key role in regulating the excitability of NAcS medium spiny neurons (MSNs) but their mechanisms of action in fear freezing are unclear. METHOD: We established an animal model of traumatic memory using conditioned fear freezing paradigm, and investigated the alterations in SK channels of NAc MSNs subsequent to fear conditioning in mice. We then utilized an adeno-associated virus (AAV) transfection system to overexpress the SK3 subunit and explore the function of the NAcS MSNs SK3 channel in conditioned fear freezing. RESULTS: Fear conditioning activated NAcS MSNs with enhanced excitability and reduced the SK channel-mediated medium after-hyperpolarization (mAHP) amplitude. The expression of NAcS SK3 were also reduced time-dependently. The overexpression of NAcS SK3 impaired conditioned fear consolidation without affecting conditioned fear expression, and blocked fear conditioning-induced alterations in NAcS MSNs excitability and mAHP amplitude. Additionally, the amplitudes of mEPSC, AMPAR/NMDAR ratio, and membrane surface GluA1/A2 expression in NAcS MSNs was increased by fear conditioning and returned to normal levels upon SK3 overexpression, indicating that fear conditioning-induced decrease of SK3 expression caused postsynaptic excitation by facilitating AMPAR transmission to the membrane. CONCLUSION: These findings show that the NAcS MSNs SK3 channel plays a critical role in conditioned fear consolidation and that it may influence PTSD pathogenesis, making it a potential therapeutic target against PTSD.