Effects of computerized working memory training on neuroplasticity in healthy individuals: A combined neuroimaging and neurotransmitter study.

Working memory (WM) is an essential cognitive function that underpins various higher-order cognitive processes. Improving WM capacity through targeted training interventions has emergered as a potential approach for enhancing cognitive abilities. The present study employed an 8-week regimen of computerized WM training (WMT) to investigate its effect on neuroplasticity in healthy individuals, utilizing neuroimaging data gathered both before and after the training. The key metrics assessed included the amplitude of low-frequency fluctuations (ALFF), voxel-based morphometry (VBM), and the spatial distribution correlations of neurotransmitter. The results indicated that post-training, compared to baseline, there was a reduction in ALFF in the medial superior frontal gyrus and an elevation in ALFF in the left middle occipital gyrus within the training group. In comparison to the control group, the training group also exhibited decreased ALFF in the anterior cingulate cortex, angular gyrus, and superior parietal lobule, along with increased ALFF in the postcentral gyrus post-training. VBM analysis revealed a significant increase in gray matter volume (GMV) in the right dorsal superior frontal gyrus after the training period, compared to the initial baseline measurement. Furthermore, the training group showed GMV increases in the dorsal superior frontal gyrus, Rolandic operculum, precentral gyrus, and postcentral gyrus when compared to the control group. In addition, significant associations were identifed between neuroimaging measurements (AFLL and VBM) and the spatial patterns of neurotransmitters such as serotonin (5-HT), dopamine (DA), and N-methyl-D-aspartate (NMDA), providing insights into the underlying neurochemical processes. These findings clarify the neuroplastic changes caused by WMT, offering a deeper understanding of brain plasticity and highlighting the potential advantages of cognitive training interventions.

Reproducibility and reliability of pancreatic pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with an extended Tofts linear (ETL) model for tissue and tumor evaluation has been established, but its effectiveness in evaluating the pancreas remains uncertain. PURPOSE: To understand the pharmacokinetics of normal pancreas and serve as a reference for future studies of pancreatic diseases. MATERIAL AND METHODS: Pancreatic pharmacokinetic parameters of 54 volunteers were calculated using DCE-MRI with the ETL model. First, intra- and inter-observer reliability was assessed through the use of the intra-class correlation coefficient (ICC) and coefficient of variation (CoV). Second, a subgroup analysis of the pancreatic DCE-MRI pharmacokinetic parameters was carried out by dividing the 54 individuals into three groups based on the pancreatic region, three groups based on age, and two groups based on sex. RESULTS: There was excellent agreement and low variability of intra- and inter-observer to pancreatic DCE-MRI pharmacokinetic parameters. The intra- and inter-observer ICCs of Ktrans, kep, ve, and vp were 0.971, 0.952, 0.959, 0.944 and 0.947, 0.911, 0.978, 0.917, respectively. The intra- and inter-observer CoVs of Ktrans, kep, ve, vp were 9.98%, 5.99%, 6.47%, 4.76% and 10.15%, 5.22%, 6.28%, 5.40%, respectively. Only the pancreatic ve of the older group was higher than that of the young and middle-aged groups (P = 0.042, 0.001), and the vp of the pancreatic head was higher than that of the pancreatic body and tail (P = 0.014, 0.043). CONCLUSION: The application of DCE-MRI with an ETL model provides a reliable, robust, and reproducible means of non-invasively quantifying pancreatic pharmacokinetic parameters.

Cognitive impairment after sleep deprivation: The role of precuneus related connectivity on the intra-individual variability changes.

OBJECTIVE: Intra-individual variability (IIV) in cognitive performance is thought to reflect the efficiency with which attentional resources are allocated in different circumstances requiring cognitive control. IIV in cognitive performance is associated with the strength of the negative correlation between task-positive network and default mode network (DMN) activity. In this study, we investigated the impact of sleep deprivation (SD) on functional connectivity (FC) between the DMN and psychomotor vigilance task-related network (PVT-RN), and its relationship with IIV in cognitive performance. METHODS: Two analyses, network-level independent component analysis (NL-ICA) and region-level (RL)-ICA, were employed to compare the coefficient of variation (CV) of the PVT between normal sleep and SD conditions across 67 healthy participants. RESULTS: After SD, in NL-ICA, the FC between the PVT-RN and DMN was positively correlated with the CV of the PVT, as well as the changes therein, compared with normal sleep. Using a mask derived from the DMN and PVT-RN, the RL-ICA revealed that 12 edges/connections between DMN and PVT independent components were associated with the CV of the PVT, with nine of these connections involving the precuneus. CONCLUSIONS: These findings suggest that the precuneus may play a crucial role in the interactions of various brain functions during the PVT, with the connections between the precuneus and frontoparietal and somatosensory networks being significantly altered after SD. Moreover, following SD, weakened negative FC between the precuneus and bilateral inferior parietal lobule may disrupt the balance between cognitive and executive control functions, leading to a decline in cognitive performance.

Effects on resting-state EEG phase-amplitude coupling in insomnia disorder patients following 1 Hz left dorsolateral prefrontal cortex rTMS.

Despite burgeoning evidence for cortical hyperarousal in insomnia disorder, the existing results on electroencephalography spectral features are highly heterogeneous. Phase-amplitude coupling, which refers to the modulation of the low-frequency phase to a high-frequency amplitude, is probably a more sensitive quantitative measure for characterizing abnormal neural oscillations and explaining the therapeutic effect of repetitive transcranial magnetic stimulation in the treatment of patients with insomnia disorder. Sixty insomnia disorder patients were randomly divided into the active and sham treatment groups to receive 4 weeks of repetitive transcranial magnetic stimulation treatment. Behavioral assessments, resting-state electroencephalography recordings, and sleep polysomnography recordings were performed before and after repetitive transcranial magnetic stimulation treatment. Forty good sleeper controls underwent the same assessment. We demonstrated that phase-amplitude coupling values in the frontal and temporal lobes were weaker in Insomnia disorder patients than in those with good sleeper controls at baseline and that phase-amplitude coupling values near the intervention area were significantly enhanced after active repetitive transcranial magnetic stimulation treatment. Furthermore, the enhancement of phase-amplitude coupling values was significantly correlated with the improvement of sleep quality. This study revealed the potential of phase-amplitude coupling in assessing the severity of insomnia disorder and the efficacy of repetitive transcranial magnetic stimulation treatment, providing new insights on the abnormal physiological mechanisms and future treatments for insomnia disorder.

Functional Connectivity Alterations During Sleep Deprivation: Investigating Key Brain Regions and Networks.

BACKGROUND: Sleep deprivation (SD) has emerged as a significant public health concern because of its adverse effects on cognition and behavior. However, the influence of circadian rhythms on SD and brain activities has been less studied. This study employed functional magnetic resonance imaging (fMRI) and functional connectivity density (FCD) metrics to investigate the interaction between sleep pressure and circadian rhythms during SD. METHODS: Thirty-six volunteers with good sleep habits underwent a sleep deprivation trial. Sleepiness was assessed using the Stanford Sleepiness Scale (SSS) at multiple time points, and fMRI scans were conducted to derive global and local FCD (gFCD and iFCD) values. This study focused on specific brain regions and networks, including the thalamus, the frontoparietal network (FPN), and the default mode network (DMN). RESULTS: Analysis indicated significant changes in gFCD and iFCD values in several key brain regions. A strong correlation was found between sleepiness and both gFCD and iFCD values in certain areas, such as the left superior temporal gyrus and left thalamus. The gFCD values in these regions showed a gradual increase across sessions, while iFCD values in the right superior frontal gyrus decreased. CONCLUSIONS: This study revealed that SD leads to enhanced functional activities in the DMN and thalamus and decreased activity in the FPN. These changes in brain activity were significantly correlated with increases in sleepiness, as measured by the SSS. Our findings underscore the importance of understanding the neural underpinnings of SD and could guide future clinical interventions aimed at mitigating its effects.

Efficient removal of Cr from aqueous solution by catechol/m-phenylenediamine nanospheres combined with Fe(II).

The discharge of chromium-containing wastewater in industrial production causes resource loss and damage to the ecological environment. Currently, various phenolamine materials have been used to remove chromium, but their harsh adsorption conditions bring many difficulties. For example, ideal chromium removal is only achieved at low pH. In this study, we synthesized catechol/m-phenylenediamine nanospheres (CMN) and combined CMN with Fe(II) for Cr removal from aqueous solutions, and Fe(II) comes from FeSO4·7H2O. CMN was characterized and analyzed by field-emission scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS), transmission electron microscopy (TEM), Fourier transformed infrared (FTIR), X-ray diffraction (XRD), X-ray photoelectron (XPS). The adsorption performance was studied through a series of adsorption experiments. When C0 = 900 mg/L and pH = 6, the maximum adsorption capacity obtained in the experiment was 977.1 mg/g. It maintains excellent adsorption properties in acidic, neutral and alkaline environments. The results of the adsorption mechanism showed that the ultra-high adsorption capacity of CMN and Fe(II) for Cr was the result of the synergistic effect of adsorption and reduction, including electrostatic attraction, reduction and coprecipitation. CMN is expected to be an ideal adsorbent for Cr removal in aqueous solution due to its low cost, high biocompatibility and high efficiency in Cr removal.

Abnormal dynamic functional connectivity after sleep deprivation from temporal variability perspective.

Sleep deprivation (SD) is very common in modern society and regarded as a potential causal mechanism of several clinical disorders. Previous neuroimaging studies have explored the neural mechanisms of SD using magnetic resonance imaging (MRI) from static (comparing two MRI sessions [one after SD and one after resting wakefulness]) and dynamic (using repeated MRI during one night of SD) perspectives. Recent SD researches have focused on the dynamic functional brain organization during the resting-state scan. Our present study adopted a novel metric (temporal variability), which has been successfully applied to many clinical diseases, to examine the dynamic functional connectivity after SD in 55 normal young subjects. We found that sleep-deprived subjects showed increased regional-level temporal variability in large-scale brain regions, and decreased regional-level temporal variability in several thalamus subregions. After SD, participants exhibited enhanced intra-network temporal variability in the default mode network (DMN) and increased inter-network temporal variability in numerous subnetwork pairs. Furthermore, we found that the inter-network temporal variability between visual network and DMN was negative related with the slowest 10% respond speed (ß = -.42, p = 5.57 × 10-4 ) of the psychomotor vigilance test after SD following the stepwise regression analysis. In conclusion, our findings suggested that sleep-deprived subjects showed abnormal dynamic brain functional configuration, which provides new insights into the neural underpinnings of SD and contributes to our understanding of the pathophysiology of clinical disorders.

Grading of Glioma: combined diagnostic value of amide proton transfer weighted, arterial spin labeling and diffusion weighted magnetic resonance imaging.

BACKGROUND: To investigate the ability of amide proton transfer (APT) weighted magnetic resonance imaging (MRI), arterial spin labeling (ASL), diffusion weighted imaging (DWI) and the combination for differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs). METHODS: Twenty-seven patients including nine LGGs and eighteen HGGs underwent conventional, APT, ASL and DWI MRI with a 3.0-T MR scanner. Histogram analyses was performed and quantitative parameters including mean apparent diffusion coefficient (ADC mean), 20th-percentile ADC (ADC 20th), mean APT (APT mean), 90th-percentile APT (APT 90th), relative mean cerebral blood flow (rCBF mean) and relative 90th-percentile CBF (rCBF 90th) were compared between HGGs and LGGs. The diagnostic performance was evaluated with receiver operating characteristic (ROC) analysis of each parameter and their combination. Correlations were analyzed among the MRI parameters and Ki-67. RESULTS: The APT values were significantly higher in the HGGs compared to the LGGs (p <  0.005), whereas ADC values were significantly lower in HGGs than LGGs (P <  0.0001). The ADC 20th and APT mean had higher discrimination abilities compared with other single parameters, with the area under the ROC curve (AUC) of 0.877 and 0.840. Adding ADC parameter, the discrimination ability of APT and rCBF significantly improved. The ADC was negatively correlated with the APT and rCBF value, respectively, while APT value was positively correlated with rCBF value. Significant correlations between ADC values and Ki-67 were also observed. CONCLUSIONS: APT and DWI are valuable in differentiating HGGs from LGGs. The combination of APT, DWI and ASL imaging could improve the ability for discriminating HGGs from LGGs.

Neural correlates of dynamic changes in working memory performance during one night of sleep deprivation.

Total sleep deprivation (TSD) is common in modern society leading to deterioration of multiple aspects of cognition. Dynamic interaction effect of circadian rhythmicity and homeostatic sleep pressure on sustained attention have been intensively investigated, while how this effect was represented on performance and cerebral responses to working memory, another important element of many neurobehavioral tasks, was not well elucidated. Thirty-six healthy subjects with intermediate chronotype performed the Sternberg working-memory task (SWMT) while undergoing functional magnetic resonance imaging every 2 hr from 10:00 p.m. on the first day to 6:00 a.m. on the second day. Using data from three imaging sessions (10:00 p.m., 04:00 a.m., and 06:00 a.m.), we found that the slowest SWMT reaction time and weakest cerebral responses were not at the end of TSD (06:00 a.m.) but during the early morning (04:00 a.m.) hours of the TSD. In addition, during this worst period of TSD, reaction time for the SWMT were found to be negatively correlated with task-related activation in the angular gyrus and positively correlated with the degree of negative correlation between the control and default networks. Our results revealed a rebound of SWMT reaction time and cerebral responses after the mid-time point of regular biological sleep night and provided more evidence that different cognitive tasks are differentially affected by sleep loss and circadian rhythmicity.

Hydrothermal synthesis of N-doped carbon dots from an ethanolamine-ionic liquid gel to construct label-free multifunctional fluorescent probes for Hg2+, Cu2+ and S2O32.

N-Doped carbon dots (NCDs) were facilely synthesized by a hydrothermal method using an ethanolamine-ionic liquid (1-carboxyethyl-3-methyl imidazole chloride) gel as a precursor. The NCDs had an average particle size of 3.4 nm and were partially crystalline and abundant in amide and hydroxyl groups and pyridinic/pyrrolic nitrogen atoms on their surfaces. In water, the NCDs showed excitation- and concentration-dependent photoluminescence (PL) properties with a high salt tolerance and a quantum yield of 24.7% under 350 nm excitation. The PL of the aqueous suspension of NCDs remained stable in a pH range of 4-11 and was significantly quenched by Hg2+ and Cu2+ owing to the strong interactions between the metal ions and the surface groups and/or nitrogen atoms of the NCDs. The possible quenching mechanism was determined to be photo-induced electron transfer. By introducing the masking agents of P2O74- and S2O32- into the aqueous suspension of NCDs, two label-free "turn-off" fluorescent probes for Hg2+ and Cu2+ with a high sensitivity and selectivity were built, respectively. Moreover, the quenched NCDs-Hg2+ system could be used as a selective "turn-on" fluorescent probe for S2O32- due to the strong affinity of S2O32- to Hg2+. The above described three probes all illustrated two good linear detection ranges for Hg2+ (0-10 and 10-50 µM), Cu2+ (0-2.5 and 2.5-40 µM) and S2O32- (0-20 and 20-80 µM), and their limits of detection were calculated to be 0.076, 0.125 and 1.17 µM. The recovery tests demonstrated that the above described probes were reliable and capable of detecting corresponding ions in tap water samples with satisfactory results.

Dynamics of cerebral responses to sustained attention performance during one night of sleep deprivation.

Total sleep deprivation (TSD) is increasingly common in modern society bringing various neurobehavioural effects. Dynamic changes of behaviour performances during TSD have been reported extensively, while the cerebral activation underlying such changes have not been elucidated clearly. This study aimed to investigate dynamic changes in cerebral responses to the fastest and slowest psychomotor vigilance task (PVT) trials during TSD. Thirty-six healthy subjects with intermediate chronotype performed the PVT while undergoing functional magnetic resonance imaging every 2 h from 22:00 hours on the first day to 06:00 hours on the second day (i.e. 22:00, 12:00, 02:00, 04:00 and 06:00 hours; a total of five imaging sessions). Behaviourally, significant time effects were found for the PVT performance. For imaging results, significant activation alterations were found in the cognitive control network and the default mode network (DMN) for the fastest and slowest PVT trials, respectively. Time-course analysis indicated that the largest differences for behavioural results and imaging results happened in session 4 and became more prominent in session 5. Our findings provide more detailed information about the process of sustained attention activation during one night of TSD and add information regarding the effect of circadian rhythmicity and homeostatic sleep pressure on regional brain responses.

Noninvasively evaluating the grading and IDH1 mutation status of diffuse gliomas by three-dimensional pseudo-continuous arterial spin labeling and diffusion-weighted imaging.

PURPOSE: To noninvasively evaluate the value of three-dimensional pseudo-continuous arterial spin labeling (3D pCASL) and diffusion-weighted imaging (DWI) in diffuse gliomas grading as well as isocitrate dehydrogenase (IDH) 1 mutation status. METHODS: Fifty-six patients with pathologically confirmed diffuse gliomas with preoperative 3D pCASL and DWI were enrolled in this study. The Student's t test and Mann-Whitney U test were used to evaluate differences in parameters of DWI and 3D pCASL between low and high grade as well as between mutant and wild-type IDH1 diffuse gliomas; receiver operator characteristic (ROC) analysis was used to assess the diagnostic performance. Subsequently, a multivariate stepwise logistic regression analysis was used to identify the independent parameters. Besides, Kruskal-Wallis H test was used to examine the differences among grades II, III, and IV diffuse gliomas. RESULTS: All parameters but CBFmean showed significant differences between low- and high-grade diffuse gliomas. In ROC analysis, the AUC of CBFmax, rCBFmean, rCBFmax, ADCmean, and ADCmin were 0.701, 0.730, 0.746, 0.810, and 0.856 respectively. Only the value of ADCmin was identified as the independent parameter in the differentiation of low- from high-grade diffuse gliomas. All parameters but CBFmean showed significant differences among the three grades. And the values of CBFmean, CBFmax, rCBFmean, and ADCmean showed significant differences between mutant and wild-type IDH1 in grade II-III astrocytoma. CONCLUSION: Both 3D pCASL and DWI could be useful tools for distinguishing low- from high-grade diffuse gliomas and have the potential to differentiate different IDH1 mutation statuses of astrocytoma.

Experimental and Theoretical Study on the Synergistic Inhibition Effect of Pyridine Derivatives and Sulfur-Containing Compounds on the Corrosion of Carbon Steel in CO2-Saturated 3.5 wt.% NaCl Solution.

The corrosion inhibition performance of pyridine derivatives (4-methylpyridine and its quaternary ammonium salts) and sulfur-containing compounds (thiourea and mercaptoethanol) with different molar ratios on carbon steel in CO2-saturated 3.5 wt.% NaCl solution was investigated by weight loss, potentiodynamic polarization, electrochemical impedance spectroscopy, and scanning electron microscopy. The synergistic corrosion inhibition mechanism of mixed inhibitors was elucidated by the theoretical calculation and simulation. The molecules of pyridine derivative compounds with a larger volume has priority to adsorb on the metal surface, while the molecules of sulfur-containing compounds with a smaller volume fill in vacancies. A dense adsorption film would be formed when 4-PQ and sulfur-containing compounds are added at a proper mole ratio.

Formaldehyde Inhibits Sexual Behavior and Expression of Steroidogenic Enzymes in the Testes of Mice.

BACKGROUND: Formaldehyde, a ubiquitous environmental pollutant, is used extensively and has been proved to impair male reproduction in mammals. However, no trials have explored whether formaldehyde affects sexual function. AIM: To evaluate the effect of long-term formaldehyde exposure on sexual behavior and to investigate the potential mechanism. METHODS: Forty C57BL/6 male mice were randomly allocated to four equally sized groups. Mice were exposed to formaldehyde at a dose of 0 (control), 0.5, 5.0, or 10.0 mg/m3 by inhalation for 60 days. OUTCOMES: Sexual behavior, body and reproductive organ weights, testosterone concentration in serum and testicular tissue, expression of steroidogenic enzymes, quality of sperm, and testicular structure were measured. RESULTS: Formaldehyde inhibited sexual behavior and decreased reproductive organ weights in mice. Serum testosterone levels and intratesticular testosterone concentrations were decreased in the formaldehyde-treated groups. Expression levels of steroidogenic enzymes, including steroidogenic acute regulatory protein, cytochrome P450 cholesterol side-chain cleavage enzyme, and 3ß-hydroxysteroid dehydrogenase (3ß-HSD), also were decreased in the testes of mice exposed to formaldehyde. Moreover, the structure of seminiferous tubules was destroyed and sperm quality decreased after formaldehyde exposure. In addition, the results indicated that the effects of formaldehyde were dose dependent. CLINICAL IMPLICATIONS: Efforts should be undertaken to decrease impairment of sexual function caused by formaldehyde exposure. STRENGTHS AND LIMITATIONS: The relatively small sample might have affected the outcomes. Further experiments are needed to study the mechanism of action of formaldehyde. CONCLUSION: Exposure to formaldehyde gas inhibited sexual behavior, caused reproductive organ atrophy, and impaired spermatogenesis in male mice, which might have been induced by suppressed expression of steroidogenic enzymes in Leydig cells and decreased testosterone synthesis. Zang Z-J, Fang Y-Q, Ji S-Y, et al. Formaldehyde Inhibits Sexual Behavior and Expression of Steroidogenic Enzymes in the Testes of Mice. J Sex Med 2017;14:1297-1306.

Frontal metabolic activity contributes to individual differences in vulnerability toward total sleep deprivation-induced changes in cognitive function.

Substantial individual differences characterize the changes induced by total sleep deprivation on cognitive functions. Despite some progress having been achieved, the mechanisms of individual differences in response to total sleep deprivation have not been clearly elucidated. Cerebral metabolism in the resting state is among the key physiological processes supporting the daily function of the brain, and may play an important role in these individual differences. Twenty-two right-handed participants (nine females and 13 males) between 20 and 26 years old completed a mathematical processing task both in resting wakefulness and after 24 h of total sleep deprivation. Fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography was used to investigate brain metabolism changes. The mathematical task was performed after the positron emission tomography scans were completed. Correlation analysis was used to investigate the correlations between cognitive performance changes and brain metabolism changes. Large inter-individual differences were found in the throughput changes, but these inter-individual differences were not associated with baseline or post-deprivation performance levels. Specifically, deterioration of throughput on the mathematical processing task was significantly correlated with metabolism changes in the superior frontal medial gyrus. These findings suggested that frontal metabolic activity contributes to individual differences in waking-induced impairment of cognitive performance.

[Theoretical investigation on the structure and vibration spectrum of D-luciferin].

In the present study, the geometry of D-Luciferin was fully optimized by the density functional theory at the B3LYP/6-311++G** and B3PW91/6-311++G** level, and the Cartesian coordinate force constant was calculated at the same level. The scaled quantum mechanism force field (SQM) method was performed to analyze the vibration spectrum. The local internal symmetry coordinates were defined using the method given by Pulay. The theoretical force field matrix, which was obtained through molecular vibration calculation programs, was transformed from Cartesian coordinates into the local internal coordinates. A normal coordinate analysis was carried out using GF matrix method developed by Wilson to give the scaled vibration frequencies and the potential energy distributions (PEDs). In order to make the vibration frequencies in good agreement with the experimental values, we empirically scale the theoretical force fields. According to PEDs, all vibration modes were assigned reliably to certain vibration frequencies. The calculated results show that the D-Luciferin molecule belongs to the point group C1 and involves 66 free degrees of vibration. All vibration modes are infrared and Raman activity. In the Infrared spectrum, the vibration frequency of the strongest absorption peak is 1,780 cm(-1), and the absorption intensity is 507 KM · mol(-1), which is mainly contributed by the stretching vibration mode of the C21==O22, double bond with the PEDs of 93%. In the Raman spectrum, the vibration frequency in the range of 1,200-1.700 cm(-1) presented strong Raman activity, the frequency of the strongest absorption peak is 1,573 cm(-1), and the absorpiton intensity is 297 KM · mol, which is mainly contributed by the stretching vibration made of the C21==N22 double bond in the five-membered ring. The results are helpful to further studying the structure and the luminescence activity of Luciferin derivatives in experiment and theory.

White matter structural topologic efficiency predicts individual resistance to sleep deprivation.

BACKGROUND: Sleep deprivation (SD) is commonplace in modern society and there are large individual differences in the vulnerability to SD. We aim to identify the structural network differences based on diffusion tensor imaging (DTI) that contribute to the individual different vulnerability to SD. METHODS: The number of psychomotor vigilance task (PVT) lapses was used to classify 49 healthy subjects on the basis of whether they were vulnerable or resistant to SD. DTI and graph theory approaches were used to investigate the topologic organization differences of the brain structural connectome between SD-vulnerable and -resistant individuals. We measured the level of global efficiency and clustering in rich club and non-rich club organizations. RESULTS: We demonstrated that participants vulnerable to SD had less global efficiency, network strength, and local efficiency but longer shortest path length compared with participants resistant to SD. Lower efficiency was mainly distributed in the right insula, bilateral thalamus, bilateral frontal, temporal, and temporal lobes. Furthermore, a disrupted subnetwork was observed that consisted of widespread connections. Moreover, the vulnerable group showed significantly decreased strength of the rich club compared with the resistant group. The strength of rich club connectivity was found to be correlated negatively with PVT performance (r = -0.395, p = 0.005). We further tested the reliability of the results. CONCLUSION: The findings revealed that individual differences in resistance to SD are related to disrupted topologic efficiency connectome pattern, and our study may provide potential connectome-based biomarkers for the early detection of the vulnerable degree to SD.

The restoration ability of a short nap after sleep deprivation on the brain cognitive function: A dynamic functional connectivity analysis.

AIMS: The brain function impairment induced by sleep deprivation (SD) is temporary and can be fully reversed with sufficient sleep. However, in many cases, long-duration recovery sleep is not feasible. Thus, this study aimed to investigate whether a short nap after SD is sufficient to restore brain function. METHODS: The data of 38 subjects, including resting state functional magnetic resonance imaging data collected at three timepoints (before SD, after 30 h of SD, and after a short nap following SD) and psychomotor vigilance task (PVT) data, were collected. Dynamic functional connectivity (DFC) analysis was used to evaluate changes in brain states among three timepoints, and four DFC states were distinguished across the three timepoints. RESULTS: Before SD, state 2 (a resting-like FC matrix) was dominant (48.26%). However, after 30 h SD, the proportion of state 2 dramatically decreased, and state 3 (still resting-like, but FCs were weakened) became dominant (40.92%). The increased proportion of state 3 positively correlated with a larger PVT "lapse" time. After a nap, the proportions of states 2 and 3 significantly increased and decreased, respectively, and the change in proportion of state 2 negatively correlated with the change in PVT "lapse" time. CONCLUSIONS: Taken together, the results indicated that, after a nap, the cognitive function impairment caused by SD may be reversed to some extent. Additionally, DFC differed among timepoints, which was also associated with the extent of cognitive function impairment after SD (state 3) and the extent of recovery therefrom after a nap (state 2).

Development of a PCSK9-targeted nanoparticle vaccine to effectively decrease the hypercholesterolemia.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein receptor (LDLR) and mediates its internalization and degradation, resulting in an increase in LDL cholesterol levels. Recently, PCSK9 emerged as a therapeutic target for hypercholesterolemia and atherosclerosis. In this study, we develop a PCSK9 nanoparticle (NP) vaccine by covalently conjugating the catalytic domain (aa 153-aa 454, D374Y) of PCSK9 to self-assembled 24-mer ferritin NPs. We demonstrate that the PCSK9 NP vaccine effectively induces interfering antibodies against PCSK9 and reduces serum lipids levels in both a high-fat diet-induced hypercholesterolemia model and an adeno-associated virus-hPCSK9D374Y-induced hypercholesterolemia model. Additionally, the vaccine significantly reduces plaque lesion areas in the aorta and macrophages infiltration in an atherosclerosis mouse model. Furthermore, we discover that the vaccine's efficacy relied on T follicular help cells and LDLR. Overall, these findings suggest that the PCSK9 NP vaccine holds promise as an effective treatment for hypercholesterolemia and atherosclerosis.

Correlation between serum tryptophan metabolism and treatment efficacy of dapoxetine in patients with premature ejaculation: A pilot study.

INTRODUCTION: Primary premature ejaculation (PPE) is a common male neurobiological disorder. Currently, there is consensus that the impairment in central serotonin (5-HT) neurotransmission constitutes a key pathogenic factor in PPE. Selective serotonin reuptake inhibitors (SSRIs) serve as the primary pharmacological intervention; however, a comprehensive elucidation of their mechanism of action remains incomplete. Owing to significant individual variability in efficacy, SSRIs exhibit a high discontinuation rate. Hence, there is an urgent need to address the selection of SSRIs for PPE treatment. OBJECTIVE: This study aims to investigate the characteristics of tryptophan (TRP) metabolism in patients with PPE and to assess its influence on the efficacy of SSRIs. METHODS: The exploratory study included a total of 16 patients with PPE and 16 control subjects who were healthy men without any sexual dysfunction. Upon enrollment in the study, all participants underwent a thorough medical history review and physical examination. Subsequently, their serum levels of TRP, its metabolites, large neutral amino acids (LNAAs), and metabolite ratios were assessed using a liquid chromatography-mass spectrometry (LC-MS) assay. After a period of 4 weeks of dapoxetine treatment, all patients with PPE underwent reassessment using the Premature Ejaculation Diagnostic Tool (PEDT) score and intravaginal ejaculatory latency time (IELT) test. RESULTS: The ratio of serum TRP to other LNAAs (TRP/LNAAs) in patients with PPE was found to be significantly lower compared to the control group (P < 0.05). Conversely, the ratio of kynurenine to TRP (KYN/TRP) was observed to be significantly higher in the PPE patients compared to the control group (P < 0.05). Including the serum TRP/LNAAs ratio and KYN/TRP ratio in the prediction model yielded the highest prediction efficiency for PPE. There was a significant negative correlation between the ratio of TRP/LNAAs before the treatment and the IELT after 4 weeks of the treatment. Additionally, there was a significant positive correlation observed between the ratio of TRP/LNAAs before the treatment and the PEDT score after 4 weeks of the treatment. CONCLUSIONS: This study demonstrates that the reduction in the TRP/LNAAs ratio and the elevation of the KYN/TRP ratio are significant characteristics associated with PPE. These findings suggest that diminished tryptophan availability in the brain and the activation of the kynurenine (KYN) pathway may play a role in the pathogenesis of PPE. The TRP/LNAAs ratio has potential as a reliable indicator of central serotonin (5-HT) levels. Considering the TRP/LNAAs ratio when selecting SSRIs for the treatment of PPE may enhance the response rate of this medication.