Codeposition Enhances the Performance of Electrochemical Aptamer-Based Sensors.

Electrochemical aptamer-based (EAB) sensors, a minimally invasive means of performing high-frequency, real-time measurement of drugs and biomarkers in situ in the body, have traditionally been fabricated by depositing their target-recognizing aptamer onto an interrogating gold electrode using a "sequential" two-step method involving deposition of the thiol-modified oligonucleotide (typically for 1 h) followed by incubation in mercaptohexanol solution (typically overnight) to complete the formation of a stable, self-assembled monolayer. Here we use EAB sensors targeting vancomycin, tryptophan, and phenylalanine to show that "codeposition", a less commonly employed EAB fabrication method in which the thiol-modified aptamer and the mercaptohexanol diluent are deposited on the electrode simultaneously and for as little as 1 h, improves the signal gain (relative change in signal upon the addition of high concentrations of the target) of the vancomycin and tryptophan sensors without significantly reducing their stability. In contrast, the gain of the phenylalanine sensor is effectively identical irrespective of the fabrication approach employed. This sensor, however, appears to employ binding-induced displacement of the redox reporter rather than binding-induced folding as its signal transduction mechanism, suggesting in turn a mechanism for the improvement observed for the other two sensors. Codeposition thus not only provides a more convenient means of fabricating EAB sensors but also can improve their performance.

Unbalanced bidirectional causal association between thyroid cancer and ER-positive breast cancer: should we recommend screening for thyroid cancer in breast cancer patients?

BACKGROUND: The association between breast cancer (BC) and thyroid cancer (TC) has been studied in several epidemiological studies. However, the underlying causal relationship between them is not yet clear. METHODS: The data from the latest large-sample genome-wide association studies (GWAS) of BC and TC were searched in the public GWAS database. The BC GWAS data included estrogen receptor (ER)-positive and negative subgroups. Two-way two-sample Mendelian Randomization (MR) was used to explore the potential causal relationship between BC and TC. Inverse variance weighting (IVW) and the MR-Egger method were used to combine the estimation of each single nucleotide variation (previous single nucleotide polymorphism). BC was taken as the result, and the effect of TC exposure was analyzed. Then, the effect of BC exposure on the result of TC was analyzed. RESULTS: Both IVW and MR-Egger results indicated that gene-driven thyroid cancer does not cause estrogen receptor-positive breast cancer and is a protective factor (ß = -1.203, SE = 4.663*10-4, P = 0.010). However, gene-driven estrogen receptor-positive breast cancer can lead to the development of thyroid cancer (ß = 0.516, SE = 0.220, P = 0.019). CONCLUSION: From the perspective of gene drive, people with TC are less likely to have ER-positive BC. In contrast, people with ER-positive BC are more likely to have TC. Therefore, it is recommended that patients with BC be screened regularly for TC.

Clinical and ultrasonic risk factors for high-volume central lymph node metastasis in cN0 papillary thyroid microcarcinoma: A retrospective study and meta-analysis.

OBJECTIVE: Papillary thyroid microcarcinoma (PTMC) comprises more than 50% of all newly detected cases of papillary thyroid carcinoma (PTC). High-volume lymph node metastasis (involving >5 lymph nodes) (hv-LNM) is associated with PTMC recurrence. In half of the clinically node-negative (cN0) PTMC patients, central lymph node metastasis (CLNM) is pathologically present. However, clinical risk factors for high-volume CLNM (hv-CLNM) in cN0 PTMC have not been defined well. Therefore, we aimed to obtain evidence for hv-CLNM risk factors in cN0 PTMC. DESIGN: Data on patients who visited our hospital between January 2020 and December 2021 were collected; a preoperative diagnosis of cN0 and a postoperative pathological confirmation of PTMC were obtained. After filtering by inclusion versus exclusion criteria, the obtained data (N = 2268) were included in the meta-analysis. Relevant studies published as of 10 April 2022, were identified from the Web of Science, PubMed, WANFANG, and CNKI databases. These eligible studies were included in the meta-analysis and the association between clinicopathological factors and hv-CLNM in cN0 PTMC was assessed. SPSS and MetaXL were used for statistical analyses. RESULTS: The meta-analysis included 10 previous studies (11,734 patients) and 2268 patients enroled in our hospital for a total of 14,002 subjects. The results of which suggested that younger age (<40, odds ratio [OR] = 3.28, 95% confidence interval [CI] = 2.75-3.92, p < .001 or <45 odds ratio [OR] = 2.93, 95% CI = 2.31-3.72, p < .001), male sex (OR = 2.81, 95% CI = 2.25-3.52, p < .001), tumour size >5 mm (OR = 1.85, 95% CI = 1.39-2.47, p < .001), multifocality (OR = 1.88, 95% CI = 1.56-2.26, p < .001), extrathyroidal extension (OR = 2.58, 95% CI = 2.02-3.30, p < .001), capsule invasion (OR = 2.02, 95% CI = 1.46-2.78, p < .001), microcalcification (OR = 3.25, 95% CI = 2.42-4.36, p < .001) and rich blood flow (OR = 1.65, 95% CI = 1.21-2.25, p = .002) were the significant factors related to an elevated hv-CLNM risk in cN0 PTMC patients. Hashimoto thyroiditis (OR = 0.76, 95% CI = 0.55-1.07, p = .114), irregular margin (versus regular margin, OR = 0.96, 95% CI = 0.68-1.33, p = .787) and hypoechoic (versus nonhypoechoic, OR = 1.27, 95% CI = 0.84-1.92, p = .261) showed no significant association with hv-CLNM. CONCLUSIONS: Younger age, tumour size >5 mm, males, extrathyroidal extension, multifocality, microcalcification, capsular invasion, and rich blood flow were the significant clinicopathological risk factors for hv-CLNM risk in cN0 PTMC patients. These predictors may compensate for the sensitivity of imaging diagnosis in the preoperative period, thus helping in the effective identification of PTMCs with an invasive phenotype.

Effects of the Novel LaPLa-Enriched Medium- and Long-Chain Triacylglycerols on Body Weight, Glycolipid Metabolism, and Gut Microbiota Composition in High Fat Diet-Fed C57BL/6J Mice.

The roles of medium- and long-chain triacylglycerols (MLCT) on health benefits under high fat diet (HFD) conditions remain in dispute. This study was conducted to investigate the effects of novel LaPLa-rich MLCT on the glycolipid metabolism and gut microbiota in HFD-fed mice when pork fat is half replaced with MLCT and palm stearin (PS). The results showed that although MLCT could increase the body weight in the mouse model, it can improve the energy utilization, regulate the glucose and lipid metabolism, and inhibit the occurrence of inflammation. Furthermore, 16S rRNA gene sequencing of gut microbiota indicated that PS and MLCT affected the overall structure of the gut microbiota to a varying extent and specifically changed the abundance of some operational taxonomic units (OTUs). Moreover, several OTUs belonging to the genera Dorea, Streptococcus, and g_Eryipelotrichaceae had a high correlation with obesity and obesity-related metabolic disorders of the host. Therefore, it can be seen that this new MLCT has different properties and functions from the previous traditional MLCT, and it can better combine the advantages of MLCT, lauric acid, and sn-2 palmitate, as well as the advantages of health function and metabolism. In summary, this study explored the effects of LaPLa-enriched lipids on glycolipid metabolism in mice, providing theoretical support for future studies on the efficacy of different types of conjugated lipids, intending to apply them to industrial production and subsequent development of related products.

Evaluate the immune-related eRNA models and signature score to predict the response to immunotherapy in thyroid carcinoma.

BACKGROUND: The functional alterations of eRNAs have been reported to be correlated with tumorigenesis. However, the roles of eRNAs in thyroid cancer (THCA) remain still unclear. This study aimed to construct an immune-related eRNA prognostic signature that could effectively predict the survival and prognosis for THCA. METHODS: The Weighted Gene Co-Expression Network Analysis (WGCNA) was performed to identify THCA-specific immune-related hub genes and immune-related eRNAs were obtained using Pearson correlation analysis. Univariate and least absolute shrinkage and selection operator (LASSO) Cox regression were conducted to construct an immune-related eRNA prognostic signature in training cohort, and the predictive capability was verified in test cohort and entire cohort. Kaplan-Meier analysis, principal component analysis (PCA), receiver operating characteristic (ROC) curves, and nomogram were used to validate the risk signature. Furthermore, CIBERSORT, ESTIMATE and ssGSEA were analyzed to explore the tumor immune microenvironment (TIME) of the risk signature, and the response of potential immunotherapeutic were also discussed. RESULTS: A total of 125 immune-related eRNAs were obtained and 16 immune-related eRNAs were significantly correlated with overall survival (OS). A 9-immune-related eRNA prognostic signature was constructed, and the risk score was identified as an independent predictor. High-risk groups were associated with a poorer OS. Immune microenvironment analysis indicated that low risk score was correlated with higher immuneScore, high immune cell infiltration, and the better response of immunotherapy. Additionally, we also detected 9 immune-related eRNA expression levels in sixty-two matched tumorous and non-tumorous tissues using qRT-PCR analysis. CONCLUSION: Our immune-related eRNA risk signature that was an independent prognostic factor was strongly correlated with the immune microenvironment and may be promising for the clinical prediction of prognosis and immunotherapeutic responses in THCA patients.

Identification and validation of a pyroptosis-related prognostic signature for thyroid cancer.

BACKGROUND: Pyroptosis is a form of programmed cell death triggered by inflammasomes. However, the roles of pyroptosis-related genes in thyroid cancer (THCA) remain still unclear. OBJECTIVE: This study aimed to construct a pyroptosis-related signature that could effectively predict THCA prognosis and survival. METHODS: A LASSO Cox regression analysis was performed to build a prognostic model based on the expression profile of each pyroptosis-related gene. The predictive value of the prognostic model was validated in the internal cohort. RESULTS: A pyroptosis-related signature consisting of four genes was constructed to predict THCA prognosis and all patients were classified into high- and low-risk groups. Patients with a high-risk score had a poorer overall survival (OS) than those in the low-risk group. The area under the curve (AUC) of the receiver operator characteristic (ROC) curves assessed and verified the predictive performance of this signature. Multivariate analysis showed the risk score was an independent prognostic factor. Tumor immune cell infiltration and immune status were significantly higher in low-risk groups, which indicated a better response to immune checkpoint inhibitors (ICIs). Of the four pyroptosis-related genes in the prognostic signature, qRT-PCR detected three of them with significantly differential expression in THCA tissues. CONCLUSION: In summary, our pyroptosis-related risk signature may have an effective predictive and prognostic capability in THCA. Our results provide a potential foundation for future studies of the relationship between pyroptosis and the immunotherapy response.

Ferroptosis-related gene signature predicts the prognosis of papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer (TC), accounting for more than 80% of all cases. Ferroptosis is a novel iron-dependent and Reactive oxygen species (ROS) reliant type of cell death which is distinct from the apoptosis, necroptosis and pyroptosis. Considerable studies have demonstrated that ferroptosis is involved in the biological process of various cancers. However, the role of ferroptosis in PTC remains unclear. This study aims at exploring the expression of ferroptosis-related genes (FRG) and their prognostic values in PTC. METHODS: A ferroptosis-related gene signature was constructed using lasso regression analysis through the PTC datasets of the Cancer Genome Atlas (TCGA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate the bioinformatics functions of significantly different genes (SDG) of ferroptosis. Additionally, the correlations of ferroptosis and immune cells were assessed through the single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT database. Finally, SDG were test in clinical PTC specimens and normal thyroid tissues. RESULTS: LASSO regression model was utilized to establish a novel FRG signature with 10 genes (ANGPTL7, CDKN2A, DPP4, DRD4, ISCU, PGD, SRXN1, TF, TFRC, TXNRD1) to predicts the prognosis of PTC, and the patients were separated into high-risk and low-risk groups by the risk score. The high-risk group had poorer survival than the low-risk group (p < 0.001). Receiver operating characteristic (ROC) curve analysis confirmed the signature's predictive capacity. Multivariate regression analysis identified the prognostic signature-based risk score was an independent prognostic indicator for PTC. The functional roles of the DEGs in the TGCA PTC cohort were explored using GO enrichment and KEGG pathway analyses. Immune related analysis demonstrated that the most types of immune cells and immunological function in the high-risk group were significant different with those in the low-risk group. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) verified the SDG have differences in expression between tumor tissue and normal thyroid tissue. In addition, cell experiments were conducted to observe the changes in cell morphology and expression of signature's genes with the influence of ferroptosis induced by sorafenib. CONCLUSIONS: We identified differently expressed FRG that may involve in PTC. A ferroptosis-related gene signature has significant values in predicting the patients' prognoses and targeting ferroptosis may be an alternative for PTC's therapy.

Identification of a Novel Cuproptosis-Related Gene Signature and Integrative Analyses in Thyroid Cancer.

Cuproptosis is a novel programmed cell death that depends on copper. The role and potential mechanism of cuproptosis-related genes (CRGs) in thyroid cancer (THCA) are still unclear. In our study, we randomly divided THCA patients from the TCGA database into a training set and a testing set. A cuproptosis-related signature consisting of six genes (SLC31A1, LIAS, DLD, MTF1, CDKN2A, and GCSH) was constructed using the training set to predict the prognosis of THCA and was verified with the testing set. All patients were classified into low- and high-risk groups according to risk score. Patients in the high-risk group had a poorer overall survival (OS) than those in the low-risk group. The area under the curve (AUC) values for 5 years, 8 years, and 10 years were 0.845, 0.885, and 0.898, respectively. The tumor immune cell infiltration and immune status were significantly higher in the low-risk group, which indicated a better response to immune checkpoint inhibitors (ICIs). The expression of six cuproptosis-related genes in our prognostic signature were verified by qRT-PCR in our THCA tissues, and the results were consistent with TCGA database. In summary, our cuproptosis-related risk signature has a good predictive ability regarding the prognosis of THCA patients. Targeting cuproptosis may be a better alternative for THCA patients.

Soft-Shelled Turtle Peptide Supplementation Modifies Energy Metabolism and Oxidative Stress, Enhances Exercise Endurance, and Decreases Physical Fatigue in Mice.

The potential of soft-shelled turtle peptides (STP) against fatigue was evaluated. Mice orally supplemented with STP significantly increased the swimming time until tiredness by 35.4-57.1%. Although not statistically significant, STP increased muscle and thymus mass. In addition, the serum lactate, ammonia, blood urea nitrogen content and creatine kinase activity in STP-fed mice were dramatically decreased when compared to the control group. Furthermore, STP supplementation increased the reserves of liver glycogen and muscle glycogen, thus improved the energy metabolism system of mice. STP treatment contributed to increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities as well as a decrease in malondialdehyde (MDA), indicating an improvement in oxidative stress protection. The Western blot (WB) results indicated that the STP supplement effectively altered the expression of oxidative stress-related protein by modulating the NRF2/KEAP1 pathway. In summary, STP affected NRF2/KEAP1 levels in skeletal muscle, leading to antioxidant activity and a slower time to exhaustion during exercise.

Single-Cell Transcriptome Analysis Reveals Inter-Tumor Heterogeneity in Bilateral Papillary Thyroid Carcinoma.

Background: The tumor microenvironment (TME) plays a pivotal role in cancer progression in papillary thyroid carcinoma (PTC), yet the composition and the phenotype of cells within the TME in bilateral PTC are poorly understood. Methods: We performed unbiased transcriptome-wide single-cell RNA sequencing (scRNA-seq) analysis on 29,561 cells from 3 pairs of bilateral PTC and 1 non-tumor thyroid sample. The results of the analysis were validated by a large-scale bulk transcriptomic dataset deposited in The Cancer Genome Atlas (TCGA) database. Results: Our integrative analysis of thyroid follicular cells revealed 42 signaling pathways enriched in malignant follicular cells, including cytokine-cytokine receptor interaction, PI3K/Akt signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and tumor necrosis factor (TNF) signaling pathway. A 6-gene signature (CXCL3, CXCL1, IL1A, CCL5, TNFRSF12A, and IL18) in the cytokine-cytokine receptor interaction pathway was constructed to predict the prognosis of patients with PTC, with high risk scores being associated with decreased overall survival [hazard ratio (HR) = 3.863, 95% CI = 2.233-6.682, p < 0.001]. Gene set variation analysis (GSVA) indicated that the pathways enriched in bilateral PTC were significantly different, indicating great heterogeneity in bilateral PTC, even with the same BRAF V600E mutation. Comprehensive analysis of T cells revealed that the proportion of CD8+ tissue-resident memory T cells expressing IFNG decreased in tumor samples with advanced N stage. Within the myeloid compartment, the ratio of suppressive M2-like to pro-inflammatory M1-like macrophages increased with advanced disease stage, which was confirmed in the bulk dataset using transcriptomic profiles. In addition, we also identified numerous biologically critical interactions among myeloid cells, T cells, and follicular cells, which were related to T-cell recruitment, M2-like macrophage polarization, malignant follicular cell progression, and T-cell inhibitory signaling. Conclusion: Our integrative analyses revealed great inter-tumor heterogeneity within the TME in bilateral PTC, which will offer assistance for precise diagnosis and treatment.

Total thyroidectomy vs thyroid lobectomy for localized medullary thyroid cancer in adults: A propensity-matched survival analysis.

BACKGROUND: This study aimed to clarify whether the extent of thyroidectomy (total thyroidectomy vs thyroid lobectomy) influences survival in adults with localized medullary thyroid cancer. METHODS: Patients with localized medullary thyroid cancer were identified using the Surveillance, Epidemiology, and End Results database (2000-2018). An independent cohort of patients with localized medullary thyroid cancer were retrospectively reviewed from three medical centers in China from 2010 to 2020. The patients were grouped by the extent of surgery (total thyroidectomy vs thyroid lobectomy). Primary end points were overall survival and disease-specific survival. RESULTS: From 1,686 patients with medullary thyroid cancer identified in SEER, 1,122 patients met inclusion for matching, with a median follow-up of 99 months. After propensity score matching, 122 patients underwent a total thyroidectomy and 122 patients underwent a thyroid lobectomy. The 10-year overall survival was 85.2% (77.9%-90.7%) and 83.1% (75.5%-90.7%) in total thyroidectomy group and in thyroid lobectomy group, respectively. The 10-year disease-specific survival was 100% and 96.8% (93.1%-100%) in total thyroidectomy group and in thyroid lobectomy group, respectively. There was no statistically significant difference in overall survival or disease-specific survival in patients with localized medullary thyroid cancer undergoing total thyroidectomy or thyroid lobectomy (hazard ratio = 0.83, 95% confidence interval 0.44-1.57, P = .57 and hazard ratio = 0.49, 95% confidence interval 0.10-2.41, P = .39, respectively). Forty-seven patients with localized medullary thyroid cancer were identified in an independent Chinese cohort (n = 29 in total thyroidectomy group vs n = 18 in thyroid lobectomy group). After a median follow-up of 47 months, there was no mortality observed in either group. CONCLUSION: This study suggests that the extent of thyroidectomy does not influence survival for patients with early-stage localized medullary thyroid cancer and that thyroid lobectomy might be adequate in this patient population.

A novel necroptosis-related gene signature associated with immune landscape for predicting the prognosis of papillary thyroid cancer.

Background: Necroptosis, a type of programmed cell death, has been implicated in a variety of cancer-related biological processes. However, the roles of necroptosis-related genes in thyroid cancer yet remain unknown. Methods: A necroptosis-related gene signature was constructed using the least absolute shrinkage and selection operator (LASSO) regression analysis and Cox regression analysis. The predictive value of the prognostic signature was validated in an internal cohort. Additionally, the single-sample gene set enrichment analysis (ssGSEA) was used to examine the relationships between necroptosis and immune cells, immunological functions, and immune checkpoints. Next, the modeled genes expressions were validated in 96 pairs of clinical tumor and normal tissue samples. Finally, the effects of modeled genes on PTC cells were studied by RNA interference approaches in vitro. Results: In this study, the risk signature of seven necroptosis-related genes was created to predict the prognosis of papillary thyroid cancer (PTC) patients, and all patients were divided into high- and low-risk groups. Patients in the high-risk group fared worse in terms of overall survival than those in the low-risk group. The area under the curve (AUC) of the receiving operating characteristic (ROC) curves proved the predictive capability of created signature. The risk score was found to be an independent risk factor for prognosis in multivariate Cox analysis. The low-risk group showed increased immune cell infiltration and immunological activity, implying that they might respond better to immune checkpoint inhibitor medication. Next, GEO database and qRT-PCR in 96 pairs of matched tumorous and non-tumorous tissues were used to validate the expression of the seven modeled genes in PTCs, and the results were compatible with TCGA database. Finally, overexpression of IPMK, KLF9, SPATA2 could significantly inhibit the proliferation, invasion and migration of PTC cells. Conclusion: The created necroptosis associated risk signature has the potential to have prognostic capability in PTC for patient outcome. The findings of this study could pave the way for further research into the link between necroptosis and tumor immunotherapy.

The prognostic value of plasma complement factor B (CFB) in thyroid carcinoma.

Stromal and immune cells are major components of tumor microenvironment (TME) and affect the growth and development of thyroid carcinoma (THCA). However, data on the exact mechanisms that define the relationship between the TME and THCA remain scant. We calculated stromal and immune cells scores and the proportion of tumor-infiltrating immune cells (TICs) by CIBERSORT and ESTIMATE based on the THCA gene expression data from the Cancer Genome Atlas (TCGA). In addition, we evaluated differentially expressed genes (DEGs) from high- and low-score groups and performed functional enrichment analysis. Furthermore, our data show a significant correlation between plasma complement factor B (CFB) and PTC development and prognosis. Gene Set Enrichment Analysis (GSEA) demonstrated that the CFB was mainly enriched in immune response pathways. The expression of CFB was positively correlated with T cells CD8, Macrophages M1, Plasma cells, T cells CD4 memory activated, T cells follicular helper and T cells regulatory (Tregs), whereas negatively correlated with Eosinophils, Macrophages M0, Macrophages M2, Mast cells resting, T cells CD4 memory resting in the TME. Finally, the expression level of CFB was verified by other cohorts from Gene Expression Omnibus (GEO) database and quantitative Real-Time PCR (qRT-PCR) analyses, which was consistent with the results of bioinformatic analysis. Taken together, our data demonstrated that the CFB could be a prognostic marker for THCA and its expression influences the infiltration of immune cells.

Predicting factors for central or lateral lymph node metastasis in conventional papillary thyroid microcarcinoma.

BACKGROUND: Optimal management for papillary thyroid microcarcinoma (PTMC) remains controversial. The purpose of this study was to explore risk factors predictive of cervical lymph node metastasis in conventional PTMCs. METHODS: Conventional PTMC patients (n = 2,404) undergoing surgery between 2010 and 2017 were grouped and analyzed according to the positivity of cervical lymph node. RESULTS: Central lymph node (CLN) metastases and lateral lymph node (LLN) metastases were observed in 915 (38.1%) and 184 (7.7%) cases, respectively. Multivariate analysis found that male (odds ratio [OR] = 1.974, p < 0.001), younger age (OR = 1.601, p < 0.001), tumor size (OR = 1.935, p < 0.001), extrathyroidal extension (ETE) (OR = 1.647, p < 0.001), multifocality (OR = 1.416, p < 0.001), and intrathyroidal spreading (OR = 3.355, p < 0.001) predicted increased CLN metastasis. In particular, younger age, multifocality, and intrathyroidal spreading were significantly associated with a high number of CLN metastases (n ≥ 5). The presence of CLN metastasis was strongly associated with LLN metastasis (OR = 5.426, p < 0.001). CONCLUSION: Male, younger age, tumor size, ETE, multifocality, and intrathyroidal spreading predict increased CLN metastasis in PTMCs. In patients with suspicious lateral lymphadenopathy, the presence of CLN metastasis is independently associated with LLN metastasis.

Cocaine Self-administration and Extinction Inversely Alter Neuron to Glia Exosomal Dynamics in the Nucleus Accumbens.

Alteration of glutamatergic synaptic plasticity in the Nucleus Accumbens (NAc) has been implicated in cocaine-seeking behaviors. Astroglial mechanisms for maintaining extracellular glutamate homeostasis through cysteine/glutamate exchanger (xCT) and glutamate transporter GLT1 are dysregulated following cocaine exposure and contribute to altered glutamatergic synaptic plasticity. However, how these astroglial proteins become dysregulated in cocaine addiction remains unknown. We recently showed that neuron to astroglial exosome signaling is essential to maintain GLT1 protein expression by transferring neuronal miR-124-3p into astrocytes to suppress GLT1-inhibiting microRNAs (miRs) in astrocytes. In the current study, by selectively labeling neuronal exosomes using CD63-GFPf/+ exosome reporter mice, we examined how the self-administration and extinction stages of the mouse cocaine self-administration model alter neuronal exosome signaling to astrocytes and microglia in the NAc. We found that cocaine (but not food) self-administration strongly reduces the internalization of neuronal exosomes, particularly in astrocytes in the NAc (but not in motor cortex), which can be effectively reversed by extinction training. In parallel, cocaine self-administration alone specifically and differentially affects activation of glial cells by decreasing GFAP expression in astrocytes but increasing Iba1 expression in microglia. However, extinction training fully reverses the increased Iba1 expression in microglia but only partially reverses the reduction of GFAP in astrocytes. Taken together, our study reveals altered in vivo dynamics of NAc neuronal exosomes in the cocaine addiction model, providing new insights about how altered neuron to glial exosome signaling may contribute to astroglial dysfunction in cocaine addiction.

Inhibitory kinetics and mechanism of flavonoids from lotus (Nelumbo nucifera Gaertn.) leaf against pancreatic α-amylase.

In this study, lotus leaf flavonoids (LLF) were found to show a notable inhibition activity on α-amylase in a mixed-type manner with IC50 value of (5.58 ±â€¯0.10) mg/mL. The intrinsic fluorescence of α-amylase was quenched by the interaction with LLF through a static quenching mechanism, and LLF-α-amylase complex was spontaneously formed mainly driven by the hydrophobic interaction and hydrogen bonding. Multispectroscopic analyses (synchronous fluorescence, three-dimensional fluorescence, circular dichroism (CD) and fourier transform infrared spectra (FT-IR)) comprehensively demonstrated that the binding of LLF to α-amylase would change the conformation and microenvironment of α-amylase, resulting in inhibiting the enzyme activity. The present study indicated that LLF had potential to be as an ingredient in functional food for the prevention of type-2 diabetes.