Endogenous Opioid Release After Orgasm in Man: A Combined PET/Functional MRI Study.

The endogenous µ-opioid receptor (MOR) system plays a key role in the mammalian reward circuit. Human and animal experiments suggest the involvement of MORs in human sexual pleasure, yet this hypothesis currently lacks in vivo support. Methods: We used PET with the radioligand [11C]carfentanil, which has high affinity for MORs, to quantify endogenous opioid release after orgasm in man. Participants were scanned once immediately after orgasm and once in a baseline state. Hemodynamic activity was measured with functional MRI during penile stimulation. Results: The PET data revealed significant opioid release in the hippocampus. Hemodynamic activity in the somatosensory and motor cortices and in the hippocampus and thalamus increased during penile stimulation, and thalamic activation was linearly dependent on self-reported sexual arousal. Conclusion: Our data show that endogenous opioidergic activation in the medial temporal lobe is centrally involved in sexual arousal, and this circuit may be implicated in orgasmic disorders.

Biasing the neurocognitive processing of videos with the presence of a real cultural other.

In the digital age, while short videos present vital events with powerful information, the presence of cultural cues may bias our processing of videos of foreign cultures. However, the underlying neurocognitive processes remain unclear. In this study, we hypothesized that cultural cues might bias video processing by either enhancing cultural perspective-taking or shifting cultural self-schema. To test these hypotheses, we used a novel paradigm in which the cultural cue was a real cultural other (the priming participants) who watched American/Chinese videos together with the primed participants. The results showed that when the cue was present, the right temporoparietal junction (rTPJ) response to videos with other cultural content was shifted, showing a priming effect. Moreover, the activity pattern in the rTPJ was more congruent with the primed culture than with the original culture, reflecting a neural biasing effect. Finally, intersubject representational similarity analysis indicated that the neural biasing effect in the rTPJ was more closely associated with cultural perspective-taking than with cultural self-schema. In summary, these findings support the perspective-taking hypothesis, suggesting that cultural cues can significantly bias our cultural mindset by altering cultural perspective-taking when we are exposed to culture-relevant naturalistic stimuli.

Application of Artificial Intelligence in Acute Coronary Syndrome: A Brief Literature Review.

Artificial intelligence (AI) is defined as a set of algorithms and intelligence to try to imitate human intelligence. Machine learning is one of them, and deep learning is one of those machine learning techniques. The application of AI in healthcare systems including hospitals and clinics has many possible advantages and future prospects. Applications of AI in cardiovascular medicine are machine learning techniques for diagnostic procedures including imaging modalities and biomarkers and predictive analytics for personalized therapies and improved outcomes. In cardiovascular medicine, AI-based systems have found new applications in risk prediction for cardiovascular diseases, in cardiovascular imaging, in predicting outcomes after revascularization procedures, and in newer drug targets. AI such as machine learning has partially resolved and provided possible solutions to unmet requirements in interventional cardiology. Predicting economically vital endpoints, predictive models with a wide range of health factors including comorbidities, socioeconomic factors, and angiographic factors comprising of the size of stents, the volume of contrast agent which was infused during angiography, stent malposition, and so on have been possible owing to machine learning and AI. Nowadays, machine learning techniques might possibly help in the identification of patients at risk, with higher morbidity and mortality following acute coronary syndrome (ACS). AI through machine learning has shown several potential benefits in patients with ACS. From diagnosis to treatment effects to predicting adverse events and mortality in patients with ACS, machine learning should find an essential place in clinical medicine and in interventional cardiology for the treatment and management of patients with ACS. This paper is a review of the literature which will focus on the application of AI in ACS.

Reinforcement learning of irrelevant stimulus-response associations modulates cognitive control.

It has been demonstrated that the Simon effect may be increased or reversed due to proportion congruency manipulation, suggesting that learned spatial irrelevant stimulus-response (S-R) associations are used to guide responses. In this study, we tested the hypothesis that learning spatial irrelevant S-R associations by rewards may show a similar modulatory effect on the Simon effect. In two experiments with the Simon task, we manipulated the contingency of stimulus-response-reward between groups. Experiment 1 showed that the Simon effect in both reaction times and error rates increased if potential performance-contingent rewards always followed congruent trials but decreased and was even reversed if rewards always followed incongruent trials. These suggest that participants used reward-strengthened spatially compatible and incompatible irrelevant S-R associations respectively to predict responses. Experiment 2 showed that the data pattern of the increase and reversal of the Simon effect showed in both rewarded and nonrewarded colors, suggesting that reward-strengthened spatial irrelevant S-R associations were used to guide responses even when there were no potential rewards. Together, these results resemble the proportion congruency effect with the Simon task, suggesting that there could be stronger conflict and attentional control when the correct response is different from the response activated by reward-strengthened irrelevant S-R associations. This suggests that reinforcement learning of irrelevant S-R associations can modulate cognitive control. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Deficiency in the short-chain acyl-CoA dehydrogenase protects mice against diet-induced obesity and insulin resistance.

Acyl-CoA dehydrogenases (CADs) participate in mitochondrial fatty acid oxidation; abnormal fatty acid oxidation is associated with obesity and related metabolic disorders. We decipher the impact of short-chain CAD (SCAD) on adiposity and insulin resistance. BALB/cBy strain mice derived from BALB/c strain are deficient in SCAD activity because of a spontaneous deletion in the acyl-CoA dehydrogenases (Acads) gene. Adiposity, lipogenesis, and insulin sensitivity were compared in BALB/c and BALB/cBy mice subjected to high-fat diets (HFDs). A whole hepatic transcriptome profiling experiment with microarrays was performed to evaluate the mechanisms by which SCAD deficiency protects against insulin resistance. Acads-deficient mice were significantly resistant to HFD-induced obesity and insulin resistance as compared with control mice. Reduced obesity results from decreased triglyceride content due to activation of AMPK in liver that would reduce hepatic content of malonyl-CoA, resulting in decreased hepatic de novo lipogenesis. Improved insulin sensitivity was associated with reduced diacylglycerol content commensurate with reduced PKC-ε activity and increased protein kinase B (AKT) activation in liver and skeletal muscle. Additionally, Acads-deficient mice displayed significantly higher expression of the endoplasmic chaperone 78-kDa glucose-regulated protein, which was further associated with the AKT activation in the primary hepatocytes. Modulation of SCAD expression may therefore be a novel therapeutic approach to manage and prevent obesity and related metabolic diseases, such as diabetes.-Chen, Y., Chen, J., Zhang, C., Yang, S., Zhang, X., Liu, Y., Su, Z. Deficiency in the short-chain acyl-CoA dehydrogenase protects mice against diet-induced obesity and insulin resistance.

Effects of Genetic Variants of Nuclear Receptor Y on the Risk of Type 2 Diabetes Mellitus.

Nuclear factor-Y (NF-Y) consists of three evolutionary conserved subunits including NF-YA, NF-YB, and NF-YC; it is a critical transcriptional regulator of lipid and glucose metabolism and adipokine biosynthesis that are associated with type 2 diabetes mellitus (T2DM) occurrence, while the impacts of genetic variants in the NF-Y gene on the risk of T2DM remain to be investigated. In the present study, we screened five single-nucleotide polymorphisms (SNPs) with the SNaPshot method in 427 patients with T2DM and 408 healthy individuals. Subsequently, we analyzed the relationships between genotypes and haplotypes constructed from these SNPs with T2DM under diverse genetic models. Furthermore, we investigated the allele effects on the quantitative metabolic traits. Of the five tagSNPs, we found that three SNPs (rs2268188, rs6918969, and rs28869187) exhibited nominal significant differences in allelic or genotypic frequency between patients with T2DM and healthy individuals. The minor alleles G, C, and C at rs2268188, rs6918969, and rs28869187, respectively, conferred a higher T2DM risk under a dominant genetic model, and the carriers of these risk alleles (either homozygotes of the minor allele or heterozygotes) had statistically higher levels of fasting plasma glucose, cholesterol, and triglycerides. Haplotype analysis showed that SNPs rs2268188, rs6918969, rs28869187, and rs35105472 formed a haplotype block, and haplotype TTAC was protective against T2DM (OR = 0.76, 95% CI = 0.33-0.82, P = 0.004), while haplotype GCCG was associated with an elevated susceptibility to T2DM (OR = 2.33, 95% CI = 1.43-3.57, P = 0.001). This study is the first ever observation to our knowledge that indicates the genetic variants of NF-YA might influence a Chinese Han individual's occurrence of T2DM.

Regulation of hepatic gluconeogenesis by nuclear factor Y transcription factor in mice.

Hepatic gluconeogenesis is essential to maintain blood glucose levels, and its abnormal activation leads to hyperglycemia and type 2 diabetes. However, the molecular mechanisms in the regulation of hepatic gluconeogenesis remain to be fully defined. In this study, using murine hepatocytes and a liver-specific knockout mouse model, we explored the physiological role of nuclear factor Y (NF-Y) in regulating hepatic glucose metabolism and the underlying mechanism. We found that NF-Y targets the gluconeogenesis pathway in the liver. Hepatic NF-Y expression was effectively induced by cAMP, glucagon, and fasting in vivo Lentivirus-mediated NF-Y overexpression in Hepa1-6 hepatocytes markedly raised the gluconeogenic gene expression and cellular glucose production compared with empty vector control cells. Conversely, CRISPR/Cas9-mediated knockdown of NF-Y subunit A (NF-YA) attenuated gluconeogenic gene expression and glucose production. We also provide evidence indicating that CRE-loxP-mediated, liver-specific NF-YA knockout compromises hepatic glucose production. Mechanistically, luciferase reporter gene assays and ChIP analysis indicated that NF-Y activates transcription of the gluconeogenic genes Pck1 and G6pc, by encoding phosphoenolpyruvate carboxykinase (PEPCK) and the glucose-6-phosphatase catalytic subunit (G6Pase), respectively, via directly binding to the CCAAT regulatory sequence motif in their promoters. Of note, NF-Y enhanced gluconeogenesis by interacting with cAMP-responsive element-binding protein (CREB). Overall, our results reveal a previously unrecognized physiological function of NF-Y in controlling glucose metabolism by up-regulating the gluconeogenic genes Pck1 and G6pc Modulation of hepatic NF-Y expression may therefore offer an attractive therapeutic approach to manage type 2 diabetes.

Unraveling the Regulation of Hepatic Gluconeogenesis.

Hepatic gluconeogenesis, de novo glucose synthesis from available precursors, plays a crucial role in maintaining glucose homeostasis to meet energy demands during prolonged starvation in animals. The abnormally increased rate of hepatic gluconeogenesis contributes to hyperglycemia in diabetes. Gluconeogenesis is regulated on multiple levels, such as hormonal secretion, gene transcription, and posttranslational modification. We review here the molecular mechanisms underlying the transcriptional regulation of gluconeogenesis in response to nutritional and hormonal changes. The nutrient state determines the hormone release, which instigates the signaling cascades in the liver to modulate the activities of various transcriptional factors through various post-translational modifications like phosphorylation, methylation, and acetylation. AMP-activated protein kinase (AMPK) can mediate the activities of some transcription factors, however its role in the regulation of gluconeogenesis remains uncertain. Metformin, a primary hypoglycemic agent of type 2 diabetes, ameliorates hyperglycemia predominantly through suppression of hepatic gluconeogenesis. Several molecular mechanisms have been proposed to be metformin's mode of action.

Polymer-assisted growth of molybdenum oxide whiskers via a sonochemical process.

Whiskers of molybdenum oxides with high aspect ratios were synthesized from peroxomolybdate precursor solutions in the presence of small amounts of poly(ethylene glycol) (PEG) via a sonochemical process at temperatures of 25-70 degrees C. Irradiation with ultrasound reduces the time needed for the growth of micrometer-sized whiskers from weeks to a few hours. The simplicity of the sonochemical approach also compares favorably to a hydrothermal/solvothermal process. The morphology, crystal structure, and other characteristics of the whiskers were characterized by scanning electron microscopy, transmission electron microscopy, selective area electron diffraction, energy-dispersive X-ray spectroscopy, wide-angle X-ray diffraction, Raman spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and the Brunauer-Emmett-Teller method. The surface area of the calcified molybdenum oxide whiskers (55.4 m2/g) was found to be much higher than those of molybdenum oxide nanofibers (35 m2/g) or nanorods (13.4 m2/g) The growth rate of various crystal faces could be postulated to be controlled by the binding of peroxomolybdate ions to pseudo-crown ether cavities formed by PEG. The reduction of molybdenum oxide to produce mixed-valent oxides and their growth could also be controlled by the reducing ability of PEG. The aspect ratio of the molybdenum oxide whiskers increased with decreasing concentration in the initial peroxomolybdate precursor solution. Whether the precursor solution species was H2Mo2O3(O2)4(H2O)2, H2MoO2(O2)2, or MoO2(OH)(OOH), the peroxide group in all the species disproportionates to give the final product MoO3 by a catalytic process. On the basis of experimental evidence of the dual role of glycols, a mechanism for the growth of the molybdenum oxide whiskers is proposed.

Mineralization of hydroxyapatite in electrospun nanofibrous poly(L-lactic acid) scaffolds.

A highly porous electrospun poly(L-lactic acid) (PLLA) nanofibrous scaffold was used as a matrix for mineralization of hydroxyapatite. The mineralization process could be initiated by immersing the electrospun scaffold in the simulated body fluids (SBF) at 37 degrees C for varying periods of time. Scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), wide-angle X-ray diffraction (WAXD), Fourier transform infrared (FTIR), and Raman spectroscopy were used to characterize the composition and the structure of the deposited mineral on the nanofiber surface. Results indicated that the mineral phase was a carbonated apatite with thin flake-like nanostructures. The effects of functional groups on the scaffold surface and anionic additives in the incubation fluids on the nucleation and growth of the mineral were investigated. It was found that a minuscule amount of anionic additives (e.g., citric acid and poly-L-aspartic acid) in the SBF could effectively inhibit the mineral growth. Surface modification of the scaffold was carried out by hydrolysis of PLLA scaffold in NaOH aqueous solution, where carboxylic acid groups were produced without compromising the scaffold integrity. The mineralization process from modified PLLA electrospun scaffolds was significantly enhanced because the calcium ions can bind to the carboxylate groups on the fiber surface.

Morphogenesis of highly ordered mixed-valent mesoporous molybdenum oxides.

Control of the size, shape, and structure of mesoporous transition metal oxide materials is important in their correlations with corresponding optoelectronic and photocatalytic properties. Highly ordered cubic phases of mixed-valent mesoporous molybdenum oxides have been prepared by the reduction and decomposition of aqueous molybdenum precursor solution in the presence of poly(ethylene oxide) under ultrasonic irradiation. Large-scale uniform molybdenum oxide particles with well-defined crystal-like morphologies (ball-like, rhombic dodecahedral, and cubic shapes) were synthesized and found to be controllable by modifying the molecular chain length of the polymeric additive. Molybdenum oxides with an average oxidation state of 4.8 form a cubic lattice of open mesoporous structures.