High-altitude environments influence emotional biases. Nonetheless, the neural mechanisms underlying emotional facial processing, which could help explain depression due to high altitudes, remain unexplored. An emotional face recognition task was used to explore the impact of high-altitude hypoxia on emotional face recognition and event-related potentials were recorded in relation to a high-altitude group (n = 22) and a low-altitude group (n = 24). The results showed that the high-altitude group had longer reaction time, lower accuracy rates, and more negative P1 and N170 amplitudes. Moreover, compared with the low-altitude group, the positive bias of the N170 component in the high-altitude group decreased, and the right hemispheric lateralization of the P1 component disappeared. These results suggest that early and late stages of facial processing are influenced by high-altitude hypoxia. The decrease in positive bias in late processing may explain depression due to high altitudes.
Objective:Migraine is a common neurological disorder, which resulting in significant societal and personal burdens. Acupuncture has attracted widespread attention in migraine prophylaxis and treatment in recent years. Although some studies have confirmed the effectiveness of acupuncture therapy in treating migraines, there is still a lack of comprehensive evaluation regarding the comparison between different types of migraines and various acupuncture therapies. Furthermore, certain special acupuncture methods have not received sufficient attention and research. Therefore, the objective of this study is to summarize and expand upon previous research, update existing evidence, and compare the efficacy of different acupuncture therapies for migraine. We aim to provide stronger evidence-based support for clinical practice through this study, thereby promoting wider application of acupuncture therapy in migraine treatment.Methods:A exhaustive and methodical search was conducted across the nine databases: PubMed, EMBASE, Web of Science, Scopus, the Cochrane Library, CBM, CNKI, WANFANG and VIP Data. The Visual Analog Scale (VAS) scores, migraine attack frequency, duration, days of attack and adverse effects were observation indicators.Results:This study included 34 studies involving a total of 3365 migraineurs. The results of the study demonstrated that acupuncture therapy reduced VAS scores of migraine patients better compared to medication (MD=-1.29, 95% CI=[-1.67,-0.92]) and exhibited greater efficacy in reducing the frequency of migraine attacks (MD=-1.95, 95% CI=[-3.06,-0.85]), the duration of attacks (MD=- 3.29, 95% CI=[-4.65,-1.93]), and days of attack (MD=-1.02, 95% CI=[-1.58,-0.47]). Significant heterogeneity suggested that different acupuncture therapies had varying effects, and that the efficacy of the same therapy may also vary in different migraine types. In the context of network meta-analysis, the SUCRA of acupuncture therapies for reducing VAS scores was ranked as special acupuncture method (98.3%), acupuncture plus medicine (71.9%), and acupuncture (54.5%). Blood-letting and cupping was the most effective treatment for lowering the frequency of migraine attacks. The most effective treatment for shortening the duration of migraine was acupuncture plus medication (81.2%). When it comes to decreasing the days of migraine, acupuncture (80.3%) came out on top. 14 studies reported the occurrence of adverse effects, of which 4 studies had no adverse effects in the test group.Conclusion:Initial findings indicate that acupuncture-related therapy exhibits superior effectiveness in the treatment of migraine and clinical decision-making should be patient-specific.
The functional connectivity of the default mode network is important in understanding the neuro-pathophysiological abnormalities in patients with non-arteritic anterior ischaemic optic neuropathy. Independent component analysis can effectively determine within and between network connectivity of different brain components. Therefore, in order to explore the association between the default mode network and other brain regions, we utilized independent component analysis to investigate the alteration of functional connectivity of the default mode network. Thirty-one patients with non-arteritic anterior ischaemic optic neuropathy and 31 healthy controls, matched for age, sex and years of education, were recruited. For patients and healthy controls, functional connectivity within and between the default mode network and other brain regions were evaluated by independent component analysis. Compared with healthy controls, patients with non-arteritic anterior ischaemic optic neuropathy showed reduced functional connectivity within the default mode network in the right cerebellar tonsil and left cerebellum posterior lobe and increased functional connectivity in the left inferior temporal and right middle frontal gyri. Furthermore, patients with non-arteritic anterior ischaemic optic neuropathy showed reduced functional connectivity between the default mode network and other brain regions in the left cerebellar tonsil and increased functional connectivity in the right putamen, left thalamus, right middle temporal and left middle frontal gyri. In conclusion, negative correlations between several clinical parameters and functional connectivity of the default mode network were observed. The study contributes to understanding the mechanism of functional reorganization in non-arteritic anterior ischaemic optic neuropathy.
This study aimed to explore the neural mechanisms underlying high-altitude (HA) adaptation and deadaptation in perceptual processes in lowlanders. Eighteen healthy lowlanders were administered a facial S1-S2 matching task that included incomplete face (S1) and complete face (S2) photographs combined with ERP technology. Participants were tested at four time points: shortly before they departed the HA (Test 1), twenty-five days after entering the HA (Test 2), and one week (Test 3) and one month (Test 4) after returning to the lowlands. Compared with those at sea level (SL), shorter reaction times (RTs), shorter latencies of P1 and N170, and larger amplitudes of complete face N170 were found in HAs. After returning to SL, compared with that of HA, the amplitude of the incomplete face P1 was smaller after one week, and the complete face was smaller after one month. The right hemisphere N170 amplitude was greater after entering HA and one week after returning to SL than at baseline, but it returned to baseline after one month. Taken together, the current findings suggest that HA adaptation increases visual cortex excitation to accelerate perceptual processing. More mental resources are recruited during the configural encoding stage of complete faces after HA exposure. The perceptual processes affected by HA exposure are reversible after returning to SL, but the low-level processing stage differs between incomplete and complete faces due to neural compensation mechanisms. The configural encoding stage in the right hemisphere is affected by HA exposure and requires more than one week but less than one month to recover to baseline.
This paper outlines a comprehensive teaching laboratory course program that centers on titration analysis, a timeless and essential technique in analytical chemistry spanning various disciplines, such as environmental science, medicine, and industry. In these fields, titration analysis is paramount for determining the concentrations of substances and evaluating their purity. The uniqueness of this course program resides in its methodical exhibition of the titration process in its entirety. This encompasses everything from manual stopcocks in glass burets to modern, precise metering pumps in automated titrators and from human-reliant indicator color changes to advanced potential indicating systems. Furthermore, the program spans conventional chemical reagents as titrants to electrogenerated titrants, providing an all-encompassing educational experience. The course design follows a structured, step-by-step pedagogy, progressing from fundamental monoprotic acid-base titration to complex polyprotic acid-base titration and from acidity-modulated redox titration to titrations involving both redox and precipitation reactions. This scaffolded approach ensures a gradual yet comprehensive understanding of titration analysis. By investing in this 8 h course program, students can anticipate achieving a profound comprehension and proficiency in the foundational principles and operational techniques of titration analysis. Moreover, they will cultivate a deep appreciation for the connotations of "titrating" and "determining" in the realm of analytical chemistry.
Objective:To explore the role of white matter hyperintensities (WMH) in predicting early neurological deterioration (END) in patients with embolic stroke of undetermined source (ESUS) without reperfusion therapy. Methods:In a retrospective analysis, 111 acute ESUS patients not treated with reperfusion therapy were enrolled. WMH severity was evaluated using the Fazekas scale, with patients categorized into mild (Fazekas score ≤ 2) or moderate-to-severe (Fazekas score ≥ 3) WMH groups. Clinical data were compared between the groups, and END was monitored within 72 hours of hospital admission. The association between WMH and END was assessed using binary logistic regression. Results:Patients with moderate-to-severe WMH were significantly older (p = 0.001) and more likely to have a history of stroke (28.6% vs 10.5%, p = 0.017) compared to the mild WMH group. The END group (n=16) presented with higher baseline NIHSS scores and a greater prevalence of moderate-to-severe WMH (p < 0.05). Binary logistic regression identified moderate-to-severe WMH (OR = 4.012, 95% CI: 1.080-14.906, p = 0.038), smoking (OR = 4.368, 95% CI: 1.171-16.293, p = 0.028), and diabetes mellitus (OR = 3.986, 95% CI: 1.007-15.789, p = 0.049) as independent predictors of END in ESUS patients. Conclusion:Moderate-to-severe WMH is an independent risk factor for END in ESUS patients not receiving reperfusion therapy, highlighting the importance of considering WMH in the clinical evaluation and management of stroke patients.
Sleep disturbance led by BMAL1-deficiency has been recognized both in rodent and non-human primate models. Yet it remained unclear how their diurnal brain oscillations were affected upon BMAL1 ablation and what caused the discrepancy in the quantity of sleep between the two species. Here, we investigated diurnal electroencephalographs of BMAL1-deficient mice and cynomolgus monkeys at young adult age and uncovered a shared defect of dysregulated high-frequency oscillations by Kullback-Leibler divergence analysis. We found beta and gamma oscillations were significantly disturbed in a day versus night manner in BMAL1-deficient monkeys, while in mice the beta band difference was less evident. Notably, the dysregulation of beta oscillations was particularly associated with psychiatric behaviors in BMAL1-deficient monkeys, including the occurrence of self-injuring and delusion-like actions. As such psychiatric phenotypes were challenging to uncover in rodent models, our results offered a unique method to study the correlation between circadian clock dysregulation and psychiatric disorders.
Introduction: Migraine is a common chronic primary headache. Cognitive dysfunction has been found in patients with migraine after repetitive attacks. We used aspecific task paradigm called Go/No-Go to explore cognitive dysfunction, especially cortical inhibition. Methods: Our study included 30 participants with migraine and 30 healthy controls. We used the Go/No-Go task to analyze different Event related potential (ERP) components,such as latency or amplitude,to explore whether differences couldbe found. The two-tailed Pearson’s R correlation was performed between the clinical characteristics of patients with migraine,such as education, clinical course, duration, frequency, pain intensity, and ERP data. To test thedegree of independence between the clinical characteristics and ERP data, we performed multiple regression. Results: At the electrophysiological level, participants with migraine had longer latencies and larger amplitudes of N2 or P3 than the control group under the Go or No-Go conditions. In addition, significant two-tailed Pearson’s R correlations werefound in different areas. In particular, clinical characteristics were correlated with No-Go-N2 latency or amplitude in the frontal, central, or temporal area and correlated with No-Go-P3 latency or amplitude in the midline area of the frontal-central-parietal lobe. Finally, linear regression analysis revealed severalindependent factors that affected the N2 or P3 components in specific cortical areas. Conclusion: Our study revealed that repetitive attacks may influence response inhibition in patients with migraine. Abnormal changes in the inhibition process or inhibition supervision have been presented and interpreted by N2/P3 components under the Go/No-Go condition. Additionally, correlations were found between sex, education, pain, and N2/P3 components located in different regions. On the basis of our results, we found that patients with migraine have poor executive function, delayed response, abnormal response inhibition, and abnormal inhibitory monitoring, meriting the design and execution of future clinical studies.
IntroductionCognitive dysfunction has frequently been found in patients with migraine. The so-called contingent negative variation (CNV) and EEG power spectral densities may be the best choices to explore the underlining pathophysiology, such as cortical inhibition and habituation.MethodsThirty migraine patients without aura and healthy controls matched for sex, age, and education were recruited separately for CNV recording. The amplitudes, latencies, and squares of different CNV components, such as oCNV, iCNV, tCNV, and PINV, were selected and analyzed. Behavioral data, such as manual reaction time (RT), were analyzed. We used the Person correlation coefficient R to analyze different ERP components in relation to clinical characteristics. A multiple regression analysis was conducted for the migraine group. Spectral analysis of EEG data from all channels using the fast Fourier transform (FFT).ResultsThe migraine group had longer A-latency, C-latency, and iCNV-latency than the control group. The migraine group had higher iCNV-amplitude, oCNV-amplitude, and tCNV-amplitude than the control group, especially those located in the occipital area. The iCNV-square, oCNV-square, tCNV-square, or PINV-square in the migraine group was significantly larger than the control group. Different correlations were found between clinical characteristics and ERP components. The delta or theta activity in the migraine group was statistically lower than in the control group.DiscussionOur study has revealed that migraine attacks may influence responsivity, pre-activation, habituation, and cortical inhibition not only on the behavioral level but also on the electrophysiological level. Abnormal changes in cortical habituation and inhibition can be interpreted as CNV components. Additionally, analyses have revealed correlations between CNV components and various factors, including age, the clinical course of the condition, attack frequency, pain intensity, and duration. Thus, repetitive migraine attacks can lead to a reduction in cortical inhibition and subsequent impairment in executive function.
Retinal ischemia‒reperfusion (I/R) injury can cause significant damage to human retinal neurons, greatly compromising their functions. Existing interventions have been proven to have little effect. Ferroptosis is a newly discovered type of programmed cell death that has been found to be involved in the process of ischemia‒reperfusion in multiple organs throughout the body. Studies have shown that it is also present in retinal ischemia‒reperfusion injury. A rat model of retinal ischemia‒reperfusion injury was constructed and treated with deferoxamine. In this study, we found the accumulation of Fe 2+ , reactive oxygen species (ROS), malondialdehyde (MDA), and the consumption of glutathione (GSH) via ELISA testing; increased expression of transferrin; and decreased expression of ferritin, SLC7A11, and GPX4 via Western blotting (WB) and real-time PCR testing. Structural signs of ferroptosis (mitochondrial shrinkage) were observed across multiple cell types, including retinal ganglion cells (RGCs), photoreceptor cells, and pigment epithelial cells. Changes in visual function were detected by F-VEP and ERG. The results showed that iron and oxidative stress were increased in the retinal ischemia‒reperfusion injury model, resulting in ferroptosis and tissue damage. Deferoxamine protects the structural and functional soundness of the retina by inhibiting ferroptosis through the simultaneous inhibition of hemochromatosis, the initiation of transferrin, and the degradation of ferritin and activating the antioxidant capacity of the System Xc-GSH-GPX4 pathway.
In Syrian hamsters, reproductive behaviors are initiated in the presence of appropriate hormonal and chemosensory cues. These cues are detected and integrated within a highly conserved pathway that converges on a small nuclear group in the lateral aspect of the medial preoptic area, the magnocellular subdivision of the medial preoptic nucleus (MPN mag). The MPN mag plays a critical role in the regulation of male mating behavior—bilateral ablation of the MPN mag eliminates copulation. The MPN mag is sexually differentiated in both neuron number and density, but not in overall volume or volume of individual neurons. The current study used unbiased stereological methods to determine when the MPN mag becomes sexually differentiated. Our data indicate that the MPN mag becomes sexually dimorphic in volume and cell number after the critical period when steroid treatment induces male sexual behavior.
Resistive switching random access memory (RRAM) is considered as one of the potential candidates for next-generation memory. However, obtaining an RRAM device with comprehensively excellent performance, such as high retention and endurance, low variations, as well as CMOS compatibility, etc., is still an open question. In this work, we introduce an insert TaO x layer into HfO x -based RRAM to optimize the device performance. Attributing to robust filament formed in the TaO x layer by a forming operation, the local-field and thermal enhanced effect and interface modulation has been implemented simultaneously. Consequently, the RRAM device features large windows (> 10 3 ), fast switching speed (~ 10 ns), steady retention (> 72 h), high endurance (> 10 8 cycles), and excellent uniformity of both cycle-to-cycle and device-to-device. These results indicate that inserting the TaO x layer can significantly improve HfO x -based device performance, providing a constructive approach for the practical application of RRAM.
Acrolein is a typical food and environmental pollutant and a risk factor for diabetes. The primary pathogenesis of diabetes is insulin deficiency and resistance. Ferroptosis is an iron-dependent cell death type, accompanying by lipid peroxide accumulation. Here, 25 mu M acrolein-induced ferroptosis is observed in mouse pancreatic beta-cell MIN6 cells as indicated by ferroptosis-related indicators, including GPX4 exhaustion, lipid peroxides accumulation, and insulin secretion impairment. Additionally, acrolein-induced ferroptosis could be reversed by Ferrostatin-1. Furthermore, endoplasmic reticulum stress (ER stress) is involved in acrolein-induced ferroptosis. The ER stress inhibits the expression of PPAR gamma, an essential gene in glucose and lipid metabolism, and facilitates lipid peroxide accumulation, leading to MIN6 cells ferroptosis and dysfunction. Moreover, resveratrol, an antioxidant natural product, may relieve ER stress and upregulate PPAR. expression, thereby inhibiting acrolein-induced ferroptosis. Thus, this study demonstrated a new perspective for the cytotoxic mechanism of acrolein on pancreatic beta-cell and the protective effect of resveratrol.
Presynaptic syntaxin binding protein 1 (STXBP1) is essential for neurotransmitter release. Heterozygous mutations in this protein cause STXBP1 encephalopathy (STXBP1-E), which is characterized by intellectual disabilities and epilepsies. Since nonhuman primates closely resemble humans, monkey models may advance studies on the pathogenesis and therapeutic treatments of STXBP1-E. We generated cynomolgus monkeys carrying STXBP1 (R292H) mutation through base editing of in vitro fertilized embryos to mimic a clinical condition. The newborn STXBP1-edited monkeys exhibited focal epilepsy, and the animal that survived beyond the first week postpartum presented typical EEG phenotypes. Biochemical analysis of brain biopsy samples showed reduced levels of STXBP1 (MUNC18-1) and SNARE complex proteins. Single-cell sequencing identified one specific cell cluster that may contribute to encephalopathy. Thus, our case report shows that base-edited STXBP1 mutant monkeys are a good animal model for STXBP1-E, and that a base-editing approach is useful for generating primate models of human genetic disorders.
INTRODUCTION: The present study aimed to explore whether there are changes in the alerting, orienting, and executive network efficiencies of attention function between high altitude immigrants and low altitude residents.METHODS: Event-related potentials (ERP) were acquired during an attention network test (ANT). The high-altitude (HA) group comprised 22 college student immigrants who were born and raised at low altitudes and had lived at a HA (11,975 ft/3650 m) for 26 mo (tests were conducted when they returned to HA for 3 mo). The low-altitude (LA) group comprised 23 college students who had never visited HA areas before.RESULTS: Compared with the LA group, the HA group had a higher pulse rate, lower oxygen saturation level, and decreased alerting and orienting effects in the behavioral results. The ERP results of the HA group showed a smaller P1 in the occipital area, a larger N1 both in the parietal and occipital areas of the alerting network, and a smaller P1 and larger N1 in the orienting network than the LA group. In the executive control network, the N2 amplitude of the HA group was more negative and the P3 amplitude of the HA group decreased in incongruent conditions.DISCUSSION: Together, these findings suggest that high-altitude migrants are less effective at alerting and orienting than low-altitude residents. For executive control function, changes in the P3 amplitudes of incongruent conditions indicated a decrease in conflict inhibition underlying the executive-control network.An X, Tao G, Zhang X, Ma H, Wang Y. Attention network changes of high-altitude migrants. Aerosp Med Hum Perform. 2022; 93(11):791-799.
The present study combined the attention network test and event-related potential approaches to investigate the neurocognitive expression of resource reduction on attention function as a result of long-term high-altitude exposure in immigrants of Tibet. When compared with low-altitude residents, the study found that high-altitude exposure decreased executive-control behavioral performance but enhanced the alerting response. Correspondingly, changes in the target N2 and P3 amplitudes indicated a decrease in conflict inhibition underlying the executive-control network. Instead, the study noted that high-altitude exposure induced additional attentional resources to the alerting stage from the aspect of a change in the cue/target N1 and P1 amplitudes, which may be derived from a reduced self-referencing function. Taken together, the current findings provided experimental evidence for the tight relationship between reduced general cognitive inhibition to the hypersensitivity of the altering attention network to external stimuli mainly observed in immigrants to Tibet.
Purpose: To investigate the possible changes in functional connectivity (FC) in patients with non-arteritic anterior ischemic optic neuropathy (NAION) using resting-state functional MRI (fMRI).Methods: Thirty-one NAION patients and 31 healthy controls were recruited and underwent resting-state fMRI scans. Regions of interest (ROIs) were defined as bilateral Brodmann’s area 17 (BA17). FC analysis was performed between the ROIs and the rest of the brain regions, and the between group comparisons of FC were performed. We conducted correlation analysis between the FC changes and the clinical variables in NAION patients.Results: Compared with healthy controls, patients with NAION showed significantly decreased FC between the left BA17 and the right inferior frontal gyrus, left caudate nucleus. As for the right BA17, patients exhibited significantly increased FC with the left olfactory gyrus and decreased FC with the right superior frontal gyrus (SFG), right insula. Moreover, FC values between the right insula and the right BA17 were positively correlated with the right side of mean sensitivity in the central visual field (r = 0.52, P < 0.01) and negatively correlated with the right side of mean defect in the central visual field (r = −0.55, P < 0.01).Conclusion: Our study indicated that patients with NAION showed significantly abnormal functional reorganization between the primary visual cortex and several other brain regions not directly related to visual function, which supports that NAION may not only be an ophthalmic disease but also a neuro-ophthalmological disease.
Objective To explore altered regional neuronal activity in patients with nonarteritic anterior ischemic optic neuropathy (NAION) and its correlation with clinical performances using the regional homogeneity (ReHo) method, which is based on resting-state functional magnetic resonance imaging (fMRI). Method Thirty-one patients with NAION (20 males, 11 females) and 31 age- and sex-matched normal controls (NCs) (20 males, 11 females) were enrolled in the study. All patients underwent ophthalmic examination, including eyesight, intraocular pressure measurement, optimal coherence tomography (OCT), visual field analysis, and fMRI scans. After ReHo was calculated, we investigated group differences in results between the patients and NCs. We analyzed the relationship between ReHo values for different brain regions in patients with NAION and intraocular pressure, visual field analysis, and OCT. A receiver operating characteristic (ROC) curve was used to assess the diagnostic ability of the ReHo method. Results Compared with NCs, patients with NAION exhibited higher ReHo values in the left middle frontal gyrus, left middle cingulate gyrus, left superior temporal gyrus, and left inferior parietal lobule. Additionally, they exhibited lower ReHo values in the right lingual gyrus, left putamen/lentiform nucleus, and left superior parietal lobule. ReHo values in the left superior parietal lobule were negatively correlated with right retinal nerve fiber layer values (r = −0.462, P = 0.01). The area under the ROC curve for each brain region indicated that the ReHo method is a credible means of diagnosing patient with NAION. Conclusion NAION was primarily associated with dysfunction in the default mode network, which may reflect its underlying neural mechanisms.
Histone-lysine N-methyltransferase 2D (KMT2D) is a major histone 3 lysine 4 (H3K4) methyltransferase and plays critical roles in regulating embryonic development,differentiation,metabolism and tumor suppression.Previous studies have reported that knockout of Kmt2d in murine resulted in severe cardiac defects and embryonic death.Hypoxia-inducible factor 1α (HIF-1α) is a key transcription factor regulating cellular responses to hypoxia.Several studies have revealed that epigenetic regulators modulate HIF-1α stability and activity.However,it is unclear whether KMT2D is involved in the transcriptional regulation of HIF-1α for its target genes under hypoxia.In this study,we observed the response of cardiomyocytes H9c2 to hypoxia in the presence or absence of Kmt2d.Under hypoxic condition,the HIF-1α,histone acetyltransferase P300,KMT2D,and H3K4me1 expression at protein levels were increased compared to the normoxic condition (P< O.05).The vascular endothelial growth factor (Vegf) mRNA level was increased compared to the normoxic condition (P<0.01).The chromatin immunoprecipitation assay (ChIP-qPCR) detected increased binding of H3K4me1 and histone 3 lysine 27 acetylation (H3K27ac) on the Vegf promoter (P<0.05).Silencing of Kmt2d resulted in decreased H3K4me1 protein level and Vegf mRNA expression under hypoxia (P<O.05).The results showed that KMT2D was involved in the regulation of HIF-1 and downstream gene Vegf expression under hypoxic condition.
The effect of emotion on prospective memory on those of different age groups and its neural mechanism in Chinese adults are still unclear. The present study investigated the effect of emotion on prospective memory during the encoding and retrieval phases in younger and older adults by using event-related potentials (ERPs). In the behavioral results, a shorter response time was found for positive prospective memory cues only in older group. In the ERP results, during the encoding phase, an increased late positive potential (LPP) was found for negative prospective memory cues in younger adults, while the amplitude of the LPP was marginally greater for positive prospective memory cues than for negative prospective memory cues in older adults. Correspondingly, younger adults showed an increased parietal positivity for negative prospective memory cues, while an elevated parietal positivity for positive prospective memory cues was found in older adults during the retrieval phase. This finding reflects the increased attentional processing of encoding and the more cognitive resources recruited to carry out a set of processes that are associated with the realization of delayed intentions when the prospective memory cues are emotional. The results reveal the effect of emotion on prospective memory during the encoding and retrieval phases in Chinese adults, modulated by aging, as shown by a positivity effect on older adults and a negativity bias in younger adults.