Neuro-cardiac-guided transcranial magnetic stimulation: Unveiling the modulatory effects of low-frequency and high-frequency stimulation on heart rate.

Transcranial magnetic stimulation (TMS) is pivotal in the field of major depressive disorder treatment. Due to its unsatisfied response rate, an increasing number of researchers have turned their attention towards optimizing TMS site localization. Since the influence of TMS in reducing heart rate (HR) offers insights into its regulatory impact on the autonomic nervous system, a novel approach, called neurocardiac-guided TMS (NCG-TMS), has been proposed to pinpoint the brain region eliciting the maximal individual reduction in HR as a personalized optimal stimulation target. The present study intends to systematically explore the effects of stimulation frequency, left and right hemispheres, stimulation positions, and individual differences on HR modulation using the NCG-TMS method. In experiment 1, low-frequency TMS was administered to 30 subjects, and it was found that low-frequency NCG-TMS significantly downregulated HR, with more significant effects in the right hemisphere than in the left hemisphere and the prefrontal cortex than in other brain areas. In experiment 2, high-frequency NCG-TMS stimulation was administered to 30 subjects, showing that high-frequency NCG-TMS also downregulated HR and had the greatest modulatory effect in the right prefrontal region. Simultaneously, both experiments revealed sizeable individual variability in the optimal stimulation site, which in turn validated the feasibility of the NCG-TMS method. In conclusion, the present experiments independently replicated the effect of NCG-TMS, provided an effect of high-/low-frequency TMS stimulation to downregulate HR, and identified a right lateralization of the HR modulation effect.

Transcutaneous Auricular Vagal Nerve Stimulation Is Effective for the Treatment of Functional Dyspepsia: A Multicenter, Randomized Controlled Study.

INTRODUCTION: Vagal nerve stimulation (VNS) can be used to modulate gastrointestinal motility, inflammation, and nociception. However, it remains unclear whether VNS is effective in adult patients with functional dyspepsia (FD). We investigated the effectiveness of transcutaneous auricular VNS (taVNS) in patients with FD. METHODS: Consecutive patients with FD meeting Rome IV criteria with modified FD Symptom Diary score ≥10 were enrolled. Patients were randomly allocated to 10-Hz taVNS (V10 group), 25-Hz taVNS (V25 group), or sham group, with 30 minutes of treatment twice a day for 4 weeks. The primary outcome was the response rate at week 4, defined as the proportion of patients whose modified FD Symptom Diary score was reduced ≥5 when compared with the baseline. Secondary outcomes included adequate relief rate and adverse events. RESULTS: A total of 300 patients were randomized to V10 (n = 101), V25 (n = 99), and sham groups (n = 100). After 4 weeks of treatment, V10 and V25 groups had a higher response rate (81.2% vs 75.9% vs 47%, both P < 0.001) and adequate relief rate (85.1% vs 80.8% vs 67%, both P < 0.05) compared with the sham group. There was no significant difference between V10 and V25 in response rate and adequate relief rate (both P > 0.05). The efficacy of taVNS (both 10 and 25 Hz) lasted at week 8 and week 12 during follow-up period. Adverse events were all mild and comparable among the 3 groups (1%-3%). DISCUSSION: Our study firstly showed that 4-week taVNS (both 10 and 25 Hz) was effective and safe for the treatment of adult FD ( clinicaltrials.gov number: NCT04668534).

Extracellular vesicles derived from PM2.5-exposed alveolar epithelial cells mediate endothelial adhesion and atherosclerosis in ApoE-/- mice.

Epidemiological studies suggested that PM2.5 (particle matters with an aerodynamic diameter ≤2.5 µm) exposure is associated with atherosclerosis. Extracellular vesicles (EVs) are messengers between intracellular communications which are important in diseases procession. At present, whether EVs derived from PM2.5-exposed alveolar epithelial cells (P-EVs) involve in atherosclerosis has not been clearly understood. This study is performed to investigate the effects of P-EVs on the development of endothelium adhesion and atherosclerosis. Here, ApoE-/- mice were randomized into different groups receiving one of the following treatments, filtered air (FA), PM2.5, PBS, PBS-treated alveolar epithelial cells-derived EVs (EVs), or P-EVs. Then the atherosclerosis level in aortas or aorta sections was evaluated by oil red O staining. The results indicated that ApoE-/- mice treated with P-EVs or PM2.5 showed more obvious atherosclerosis plaques in aortas and aortic arches than those treated with EVs or PBS. Endothelial cells (ECs) were treated with PBS, EVs, P-EVs, or PM2.5. The adhesion property, miRNAs level and expressions of IκBα, phosphorylated IκBα, NF-κB p65, phosphorylated NF-κB p65, and VCAM1 in ECs were determined. It was found that P-EVs activated IκBα-NF-κB-VCAM1 signaling and increased adhesion of ECs, and such effects could be reversed by adalimumab (the TNF-α inhibitor) or miR-326-3p inhibitor. Further study suggested that P-EVs induced upregulation of TNF-α and miR-326-3p in recipient ECs and contributed to the phosphorylation of NF-κB p65. Collectively, EVs derived from PM2.5-exposed alveolar epithelial cells played an important role in the development of atherosclerosis via activating IκBα-NF-κB-VCAM1 signaling.

Acylhydrazone Functionalized Triphenylamine-Based Fluorescent Probe for Cu2+: Tunable Structures of Conjugated Bridge and Its Practical Application.

Novel fluorescent probes were constructed for the convenient and rapid analysis of Cu2+ ions, taking advantages of the the triphenylamine backbone as chromophore and acylhydrazone group as the Cu2+ recognition site. Especially, probe T2 could act as a dual-channel probe towards Cu2+ through both fluorescent and colorimetric method. Through the fluorescent method, the detection limit of probe T2 was calculated to be as low as 90 nmol/L and there was a good linear relationship between the intensity change and the concentration of Cu2+ ions. By virtue of the two-phase liquid-liquid extraction method, probe T2 could be successfully applied in practical extraction and separation of Cu2+. Furthermore, by applying a "turn-off-turn-on" circle, compound T2 could act as a sensitive probe towards S2- anions through the indirect approach and the detection limit of complex T2-Cu2+ for S2- anion was found to be 110 nmol/L.

Risk of Epilepsy Following Traumatic Brain Injury: A Systematic Review and Meta-analysis.

BACKGROUND: Limited evidence has explored the impact of traumatic brain injury (TBI) on posttraumatic epilepsy with control cohort for comparison. In addition, we could not find any review to identify the effect of TBI on the outcomes. Thus, we conducted this study to compare the risk of epilepsy between individuals with TBI and without TBI. METHODS: Systematic and comprehensive search was carried out in the following databases and search engines: EMBASE, Cochrane, MEDLINE, ScienceDirect, and Google Scholar from 1954 until January 2022. The Newcastle Ottawa (NO) Scale was utilized to assess the risk of bias. Meta-analysis was carried out using the random-effects model, and pooled odds ratio (OR) along with 95% CI was reported. RESULTS: In total, we included 10 studies satisfying inclusion criteria. Most studies had good to satisfactory quality. The pooled OR was 4.25 (95% CI, 1.77-10.25; I2 = 100%), indicating that the individuals with TBI had 4.25 times higher risk of having epilepsy than individuals without TBI, and this association was statistically significant ( P = .001). Subgroup analysis based on the years of follow-up revealed that the patients within 5 years post-TBI had the highest risk of epilepsy (pooled OR = 7.27; 95% CI, 3.61-14.64). CONCLUSION: Individuals with TBI had a significantly higher risk of epilepsy than the individuals without TBI, irrespective of the duration of the injury. Hence, long-term follow-up of the individuals with TBI is necessary to prevent any adverse consequences.

The correlation between dynamic functional architecture and response to electroconvulsive therapy combined with antipsychotics in schizophrenia.

Attempts to determine why some patients respond to electroconvulsive therapy (ECT) are valuable in schizophrenia. Schizophrenia is associated with aberrant dynamic functional architecture, which might impact the efficacy of ECT. We aimed to explore the relationship between pre-treatment temporal variability and ECT acute efficacy. Forty-eight patients with schizophrenia and 30 healthy controls underwent functional magnetic resonance imaging to examine whether patterns of temporary variability of functional architecture differ between high responders (HR) and low responders (LR) at baseline. Compared with LR, HR exhibited significantly abnormal temporal variability in right inferior front gyrus (IFGtriang.R), left temporal pole (TPOsup.L) and right middle temporal gyrus (MTG.R). In the pooled patient group, ∆PANSS was correlated with the temporal variability of these regions. Patients with schizophrenia with a distinct dynamic functional architecture appear to reveal differential response to ECT. Our findings provide not only an understanding of the neural functional architecture patterns that are found in schizophrenia but also the possibility of using these measures as moderators for ECT selection.

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.

Reassessment of the Effect of Transcutaneous Auricular Vagus Nerve Stimulation Using a Novel Burst Paradigm on Cardiac Autonomic Function in Healthy Young Adults.

BACKGROUND: Transcutaneous auricular vagus nerve stimulation (taVNS) may modulate cardiac autonomic function. However, the response rate of the traditional tonic paradigm is low, and the results remain inconsistent. A recent pilot study presented a novel burst paradigm to activate the cardiac parasympathetic system, which might offer a new approach to treat cardiac autonomic function. The present study reassessed the effect of burst taVNS on modulating heart rate variability and explored the difference between burst and traditional tonic paradigms. MATERIALS AND METHODS: Forty-two young adults were recruited for this study. Each participant underwent three types of taVNS with sham (30 sec of stimulation), tonic (25 Hz, 500 µsec), and burst (five pulses at 500 Hz every 200 msec) paradigms, respectively, with simultaneous electrocardiogram recording. One-way analysis of variance, multivariate analysis of variance, and linear regression were used for analysis. Multiple testing was performed using Bonferroni correction. RESULTS: Both burst and tonic paradigms induced a significant decrease in heart rate, which continued until poststimulation, and increased cardiac parasympathetic activity. Moreover, two parasympathetic system indicators showed significant increase only in burst taVNS. The response rates during burst (35.7%) and tonic (38.1%) stimulations were both higher than that during sham stimulation (11.9%). The response to taVNS showed parameter specificity with few nonresponders to the tonic paradigm responding to the burst paradigm. The overall response rate increased from 38.1% in tonic taVNS to 54.8% in taVNS using both burst and tonic paradigms. For both burst and tonic responders, baseline cardiac parasympathetic activity was found to be significantly negatively correlated with changes during stimulation. CONCLUSION: The burst parameter could be used as an alternative strategy for regulating cardiac parasympathetic function by taVNS, which has the potential to be used as a complementary paradigm to traditional tonic taVNS for promoting clinical treatment efficacy.

Transcriptome profiling provides insights into molecular mechanism in Peanut semi-dwarf mutant.

BACKGROUND: Plant height, mainly decided by main stem height, is the major agronomic trait and closely correlated to crop yield. A number of studies had been conducted on model plants and crops to understand the molecular and genetic basis of plant height. However, little is known on the molecular mechanisms of peanut main stem height. RESULTS: In this study, a semi-dwarf peanut mutant was identified from 60Co γ-ray induced mutant population and designated as semi-dwarf mutant 2 (sdm2). The height of sdm2 was only 59.3% of its wild line Fenghua 1 (FH1) at the mature stage. The sdm2 has less internode number and short internode length to compare with FH1. Gene expression profiles of stem and leaf from both sdm2 and FH1 were analyzed using high throughput RNA sequencing. The differentially expressed genes (DEGs) were involved in hormone biosynthesis and signaling pathways, cell wall synthetic and metabolic pathways. BR, GA and IAA biosynthesis and signal transduction pathways were significantly enriched. The expression of several genes in BR biosynthesis and signaling were found to be significantly down-regulated in sdm2 as compared to FH1. Many transcription factors encoding genes were identified as DEGs. CONCLUSIONS: A large number of genes were found differentially expressed between sdm2 and FH1. These results provide useful information for uncovering the molecular mechanism regulating peanut stem height. It could facilitate identification of causal genes for breeding peanut varieties with semi-dwarf phenotype.

Extracellular Vesicles Derived from Adipose Mesenchymal Stem Cells Alleviate PM2.5-Induced Lung Injury and Pulmonary Fibrosis.

BACKGROUND Exposure to PM2.5 (fine particulate matter ≤2.5 µm in aerodynamic diameter) in air increases the risk of lung injury and pulmonary fibrosis (PF). Extracellular vesicles (EVs) derived from adipose mesenchymal stem cells (ADSCs) have been identified as a potential treatment based on the proteins or RNAs delivery and immunomodulatory properties. Here, we assessed the protective effects and mechanisms of ADSCs-EVs on PM2.5-induced lung injury or PF. MATERIAL AND METHODS Rats (male, 6 weeks old) were exposed to PBS or PM2.5 (1.5 mg/kg/day) for 3 days a week for 4 weeks. ADSCs-EVs were extracted by ultracentrifugation. PBS and ADSCs-EVs were administrated through intratracheal instillation. After the end of exposure, the rats were anesthetized and killed. Lung tissues with different treatments were collected for Western blot analysis and HE, IHC, and IF staining analysis. Cells exposed to PM2.5 or "PM2.5+ADSCs-EVs" in vitro were also collected for further Western blotting, qRT-PCR, and IF staining evaluation. RESULTS The results indicated that the initial response of lungs exposed to PM2.5 was lung injury with oxidative stress and inflammation. Long-term PM2.5 exposure resulted in obvious PF in rats. Treatment with ADSCs-EVs decreased PM2.5-induced apoptosis and necrosis in type II alveolar epithelial cells and alleviated lung injury and PF in rats. ADSCs-EVs suppressed reactive oxygen species (ROS) levels and inflammation induced by PM2.5. Furthermore, ADSCs-EVs inhibited TGF-ßRI by transferring let-7d-5p and further mitigated PF. CONCLUSIONS Our results suggest that EVs derived from ADSCs can alleviate PM2.5-induced lung injury and PF.

Spalt-Like Protein 4 (SALL4) Promotes Angiogenesis by Activating Vascular Endothelial Growth Factor A (VEGFA) Signaling.

BACKGROUND Spalt-like protein 4 (SALL4) is a nuclear transcription factor central to early embryonic development, especially for regulating pluripotency of embryonic stem cells (ESCs) and sustaining ESCs self-renewal. Aberrant re-expression of SALL4 in adult tissues is involved in tumorigenesis and cancer progression. However, the role of SALL4 in angiogenesis remains elusive. Here, we determined the potential action of SALL4 on proliferation, migration, and tube formation of endothelial cells. MATERIAL AND METHODS HUVECs were infected with lentiviral particles expressing shRNA against SALL4. QRT-PCR and immunoblotting analysis were carried out to evaluate knockdown efficiency at mRNA and protein levels. Cell proliferation was measured by CCK-8 assay and flow cytometry was conducted to analyze cell cycle distribution. Wound-healing and Transwell migration assays were performed to evaluate cell motility. In addition, we determined the role of SALL4 on angiogenesis by tube formation assay, and Western blot analysis was used to assess the effect of SALL4 downregulation on VEGFA expression. RESULTS We found that SALL4 downregulation resulted in decreased proliferation. Cell cycle analysis revealed that SALL4 knockdown impeded cell cycle progression and induced cell cycle arrest at G1 phase. We also found that silencing of SALL4 decreased the capacity of wound healing and cell migration in HUVECs. Furthermore, tube formation assay showed that loss of SALL4 inhibited HUVECs angiogenesis. We also observed that SALL4 knockdown reduced the level of VEGFA in HUVECs. CONCLUSIONS In conclusion, these results support that by promoting proliferation, cell cycle progression, migration, and tube formation, SALL4 is involved in the process of angiogenesis through modulating VEGFA expression.

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.

pH low insertion peptide mediated cell division cycle-associated protein 1 -siRNA transportation for prostatic cancer therapy targeted to the tumor microenvironment.

Prostate cancer (PCa) is a common malignancy in male urinary system. Cell division cycle-associated protein 1 (CDCA1) is expressed highly in many cancer cells. Yet, whether CDCA1 play an important role in PCa progression is uncertain. pH low insertion peptide (pHLIP), a PH-induced transmembrane structure, can pass through the cell membrane into intracellular in an acidic environment. In this study, we try to confirm the expression status of CDCA1 in the PCa patients' tissues and PCa cell line. In addition, to make the CDCA1-siRNA efficiently targeting the PCa cells, pHLIP and CDCA1-siRNA were combined with disulfide bond to become effector molecules. By the characteristics of the pHLIP allosteric occurring in cancer tissue acidic microenvironment, CDCA1-siRNA may be transported specificity into prostatic cancer cells and released in the cytoplasm. The interference effect of the effector molecules on the CDCA1 was detected in vitro and in vivo. The results showed that CDCA1 was highly expressed in PCa cell line and human PCa clinical samples. Knock down CDCA1 significantly inhibit the growth and promote the apoptosis of prostatic cancer cells. In the intracellular translocation experiment, CDCA1-siRNA could be delivered into cytoplasma at pH 6.2, but not at pH 7.4. In the in vivo test, the tumor size was reduced obviously in the NOD/SCID mice treated with pHLIP-CDCA1-siRNA compared to the CDCA1-siRNA and the bioluminescent signal of Cy5-pHLIP-CDCA1-siRNA was focused detected in the tumor site. Our findings indicated that CDCA1 might be a very key molecule regulating survival and proliferation of PCa. pHLIP-CDCA1-siRNA might be a promising targeting therapy for PCa.

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.

Combined Treatment with Valproic Acid and 5-Aza-2'-Deoxycytidine Synergistically Inhibits Human Clear Cell Renal Cell Carcinoma Growth and Migration.

BACKGROUND Histone acetylation and DNA methylation are important mammalian epigenetic modifications that participate in the regulation of gene expression. Because dysregulation of histone deacetylase and DNA methyltransferases are hallmarks of malignancy, they have become promising therapeutic targets. In this study, we explored the anti-tumor activity of valproic acid (VPA), a histone deacetylase inhibitor (HDACi) and 5-Aza-2'-deoxycytidine (5-Aza), an inhibitor of DNA methyltransferases, on renal cell carcinoma (RCC) cell lines 786-O and 769-P. MATERIAL AND METHODS The cell proliferation was detected by xCELLigence RTCA DP Instrument, viability by CCK8 assay, cell apoptosis and cell cycle by flow cytometry, and cell migration by wound healing assay, Transwell assay and xCELLigence RTCA DP Instrument. RESULTS We discovered that VPA and 5-Aza could individually induce decreased viability and have an inhibitory effect on the proliferation of 786-O and 769-P cells. This anti-growth effect was more pronounced when the cells were treated with both VPA and 5-Aza. The combination of VPA and 5-Aza also elicited more apoptosis and produced more cell cycle arrest in the G1 phase for both cell lines. On the other hand, treatment of RCC cells with VPA, 5-Aza, or a combination of both resulted in slow wound healing and impaired migration. CONCLUSIONS These findings clearly demonstrated that VPA combined with 5-Aza could significantly increase anti-RCC effects by inhibiting cellular proliferation, inducing apoptosis, promoting cell cycle arrest and prohibiting the migration of human RCC cells.

Disturbed Brain Activity in Resting-State Networks of Patients with First-Episode Schizophrenia with Auditory Verbal Hallucinations: A Cross-sectional Functional MR Imaging Study.

Purpose To investigate auditory verbal hallucination (AVH)-specific patterns of brain activity within the resting-state networks (RSNs) that have been proposed to underpin the neural mechanisms of schizophrenia (SZ). Materials and Methods This cross-sectional study was approved by the local ethics committee, and written informed consent was obtained from all participants prospectively recruited. Independent component analysis was used to investigate RSNs in 17 patients with first-episode untreated SZ with AVHs, 15 patients with SZ without AVHs, and 19 healthy control subjects who underwent resting-state functional magnetic resonance imaging. Dual regression was implemented to perform between-group analysis. Regional brain function was then explored within RSNs by using the amplitude of low-frequency fluctuation. Two-sample t tests were used to compare regional brain function between the two patient groups, and Pearson correlation analysis was used to characterize the relationship between imaging findings and severity of AVHs. Receiver operating characteristic analysis was used to evaluate the diagnostic performance of these brain function measures. Results Independent component analysis demonstrated symptom-specific abnormal disrupted coactivation within the auditory, default mode, executive, motor, and frontoparietal networks and was pronounced in the auditory cortex, supramarginal gyrus, insula, putamen, dorsolateral prefrontal cortex, angular gyrus, precuneus, and thalamus (P < .05 with false discovery rate correction). Amplitude of low-frequency fluctuation analysis demonstrated similar patterns within these RSNs (P < .05 with false discovery rate correction). Furthermore, a positive correlation between the degree of coactivation within the motor network and the severity of AVHs was observed in patients with SZ with AVHs (r = 0.67, P = .003). The area under the receiver operating characteristic curve was 0.76-0.90 for all RSNs. Conclusion These findings indicate that dysfunctional brain regions are involved in auditory processing, language production and monitoring, and sensory information filtering in patients with SZ with AVHs, which may be helpful in furthering the understanding of pathophysiological correlates of AVHs in SZ. Online supplemental material is available for this article.

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.

Expertise modulates local regional homogeneity of spontaneous brain activity in the resting brain: an fMRI study using the model of skilled acupuncturists.

Studies on training/expertise-related effects on human brain in context of neuroplasticity have revealed that plastic changes modulate not only task activations but also patterns and strength of internetworks and intranetworks functional connectivity in the resting state. Much has known about plastic changes in resting state on global level; however, how training/expertise-related effect affects patterns of local spontaneous activity in resting brain remains elusive. We investigated the homogeneity of local blood oxygen level-dependent fluctuations in the resting state using a regional homogeneity (ReHo) analysis among 16 acupuncturists and 16 matched nonacupuncturists (NA). To prove acupuncturists' expertise, we used a series of psychophysical tests. Our results demonstrated that, acupuncturists significantly outperformed NA in tactile-motor and emotional regulation domain and the acupuncturist group showed increased coherence in local BOLD signal fluctuations in the left primary motor cortex (MI), the left primary somatosensory cortex (SI) and the left ventral medial prefrontal cortex/orbitofrontal cortex (VMPFC/OFC). Regression analysis displayed that, in the acupuncturists group, ReHo of VMPFC/OFC could predict behavioral outcomes, evidenced by negative correlation between unpleasantness ratings and ReHo of VMPFC/OFC and ReHo of SI and MI positively correlated with the duration of acupuncture practice. We suggest that expertise could modulate patterns of local resting state activity by increasing regional clustering strength, which is likely to contribute to advanced local information processing efficiency. Our study completes the understanding of neuroplasticity changes by adding the evidence of local resting state activity alterations, which is helpful for elucidating in what manner training effect extends beyond resting state.

Altered fecal microbiota composition associated with food allergy in infants.

Increasing evidence suggests that perturbations in the intestinal microbiota composition of infants are implicated in the pathogenesis of food allergy (FA), while the actual structure and composition of the intestinal microbiota in human beings with FA remain unclear. Microbial diversity and composition were analyzed with parallel barcoded 454 pyrosequencing targeting the 16S rRNA gene hypervariable V1-V3 regions in the feces of 34 infants with FA (17 IgE mediated and 17 non-IgE mediated) and 45 healthy controls. Here, we showed that several key FA-associated bacterial phylotypes, but not the overall microbiota diversity, significantly changed in infancy fecal microbiota with FA and were associated with the development of FA. The proportion of abundant Bacteroidetes, Proteobacteria, and Actinobacteria phyla were significantly reduced, while the Firmicutes phylum was highly enriched in the FA group (P < 0.05). Abundant Clostridiaceae 1 organisms were prevalent in infants with FA at the family level (P = 0.016). FA-enriched phylotypes negatively correlated with interleukin-10, for example, the genera Enterococcus and Staphylococcus. Despite profound interindividual variability, levels of 20 predominant genera were significantly different between the FA and healthy control groups (P < 0.05). Infants with IgE-mediated FA had increased levels of Clostridium sensu stricto and Anaerobacter and decreased levels of Bacteroides and Clostridium XVIII (P < 0.05). A positive correlation was observed between Clostridium sensu stricto and serum-specific IgE (R = 0.655, P < 0.001). The specific microbiota signature could distinguish infants with IgE-mediated FA from non-IgE-mediated ones. Detailed microbiota analysis of a well-characterized cohort of infants with FA showed that dysbiosis of fecal microbiota with several FA-associated key phylotypes may play a pathogenic role in FA.

Quantitative assessment of the association between TP53 Arg72Pro polymorphism and risk of glioma.

Many studies have investigated on the association between TP53 Arg72Pro polymorphism and risk of glioma, but the impact of TP53 Arg72Pro polymorphism on glioma risk is unclear owing to the obvious inconsistence among those studies. To shed light on these inconclusive findings and get a quantitative assessment of the association between the TP53 Arg72Pro polymorphism and risk of glioma, we conducted a meta-analysis of eligible studies. We searched PubMed and Embase databases for studies investigating on the association between the TP53 Arg72Pro polymorphism and risk of glioma. The pooled odds ratios (OR) with their 95% confidence intervals (95% CI) was calculated to assess the association between the TP53 Arg72Pro polymorphism and risk of glioma. A total of 12 studies were finally included into the meta-analysis. Meta-analysis of the 12 studies showed that TP53 Arg72Pro polymorphism was not associated with the risk of glioma (OR(Pro vs. Arg) = 1.07, 95% CI 0.93∼1.22; OR(ProPro vs. ArgArg) = 1.02, 95% CI 0.85∼1.22; OR(ProPro/ArgPro vs. ArgArg )= 1.06, 95% CI 0.85∼1.34; and OR(ProPro vs. ArgArg/ArgPro) = 1.07, 95% CI 0.91∼1.27). Subgroup analyses by ethnicity further identified that TP53 Arg72Pro polymorphism was not associated with the risk of glioma in Caucasians. However, there was a mild association between the TP53 Arg72Pro polymorphism and risk of glioma in Asians (OR(ProPro vs. ArgArg/ArgPro) = 1.42, 95% CI 1.00∼2.02). Thus, there is limited evidence for the association between the TP53 Arg72Pro polymorphism and risk of glioma, and more studies are needed to provide a more comprehensive assessment of the association in Asians.