Auditory change detection and visual selective attention: association between MMN and N2pc.

While the auditory and visual systems each provide distinct information to our brain, they also work together to process and prioritize input to address ever-changing conditions. Previous studies highlighted the trade-off between auditory change detection and visual selective attention; however, the relationship between them is still unclear. Here, we recorded electroencephalography signals from 106 healthy adults in three experiments. Our findings revealed a positive correlation at the population level between the amplitudes of event-related potential indices associated with auditory change detection (mismatch negativity) and visual selective attention (posterior contralateral N2) when elicited in separate tasks. This correlation persisted even when participants performed a visual task while disregarding simultaneous auditory stimuli. Interestingly, as visual attention demand increased, participants whose posterior contralateral N2 amplitude increased the most exhibited the largest reduction in mismatch negativity, suggesting a within-subject trade-off between the two processes. Taken together, our results suggest an intimate relationship and potential shared mechanism between auditory change detection and visual selective attention. We liken this to a total capacity limit that varies between individuals, which could drive correlated individual differences in auditory change detection and visual selective attention, and also within-subject competition between the two, with task-based modulation of visual attention causing within-participant decrease in auditory change detection sensitivity.

Wearable device-measured moderate to vigorous physical activity and risk of degenerative aortic valve stenosis.

BACKGROUND AND AIMS: Physical activity has proven effective in preventing atherosclerotic cardiovascular disease, but its role in preventing degenerative valvular heart disease (VHD) remains uncertain. This study aimed to explore the dose-response association between moderate to vigorous physical activity (MVPA) volume and the risk of degenerative VHD among middle-aged adults. METHODS: A full week of accelerometer-derived MVPA data from 87 248 UK Biobank participants (median age 63.3, female: 56.9%) between 2013 and 2015 were used for primary analysis. Questionnaire-derived MVPA data from 361 681 UK Biobank participants (median age 57.7, female: 52.7%) between 2006 and 2010 were used for secondary analysis. The primary outcome was the diagnosis of incident degenerative VHD, including aortic valve stenosis (AS), aortic valve regurgitation (AR), and mitral valve regurgitation (MR). The secondary outcome was VHD-related intervention or mortality. RESULTS: In the accelerometer-derived MVPA cohort, 555 incident AS, 201 incident AR, and 655 incident MR occurred during a median follow-up of 8.11 years. Increased MVPA volume showed a steady decline in AS risk and subsequent AS-related intervention or mortality risk, levelling off beyond approximately 300 min/week. In contrast, its association with AR or MR incidence was less apparent. The adjusted rates of AS incidence (95% confidence interval) across MVPA quartiles (Q1-Q4) were 11.60 (10.20, 13.20), 7.82 (6.63, 9.23), 5.74 (4.67, 7.08), and 5.91 (4.73, 7.39) per 10 000 person-years. The corresponding adjusted rates of AS-related intervention or mortality were 4.37 (3.52, 5.43), 2.81 (2.13, 3.71), 1.93 (1.36, 2.75), and 2.14 (1.50, 3.06) per 10 000 person-years, respectively. Aortic valve stenosis risk reduction was also observed with questionnaire-based MVPA data [adjusted absolute difference Q4 vs. Q1: AS incidence, -1.41 (-.67, -2.14) per 10 000 person-years; AS-related intervention or mortality, -.38 (-.04, -.88) per 10 000 person-years]. The beneficial association remained consistent in high-risk populations for AS, including patients with hypertension, obesity, dyslipidaemia, and chronic kidney disease. CONCLUSIONS: Higher MVPA volume was associated with a lower risk of developing AS and subsequent AS-related intervention or mortality. Future research needs to validate these findings in diverse populations with longer durations and repeated periods of activity monitoring.

Loss of m6A demethylase ALKBH5 alleviates hypoxia-induced pulmonary arterial hypertension via inhibiting Cyp1a1 mRNA decay.

BACKGROUND: Hypoxia-induced pulmonary artery hypertension (HPH) is a complication of chronic hypoxic lung disease and the third most common type of pulmonary artery hypertension (PAH). Epigenetic mechanisms play essential roles in the pathogenesis of HPH. N6-methyladenosine (m6A) is an important modified RNA nucleotide involved in a variety of biological processes and an important regulator of epigenetic processes. To date, the precise role of m6A and regulatory molecules in HPH remains unclear. METHODS: HPH model and pulmonary artery smooth muscle cells (PASMCs) were constructed from which m6A changes were observed and screened for AlkB homolog 5 (Alkbh5). Alkbh5 knock-in (KI) and knock-out (KO) mice were constructed to observe the effects on m6A and evaluate right ventricular systolic pressure (RVSP), left ventricular and septal weight [RV/(LV + S)], and pulmonary vascular remodeling in the context of HPH. Additionally, the effects of Alkbh5 knockdown using adenovirus were examined in vitro on m6A, specifically in PASMCs with regard to proliferation, migration and cytochrome P450 1A1 (Cyp1a1) mRNA stability. RESULTS: In both HPH mice lung tissues and hypoxic PASMCs, a decrease in m6A was observed, accompanied by a significant up-regulation of Alkbh5 expression. Loss of Alkbh5 attenuated the proliferation and migration of hypoxic PASMCs in vitro, with an associated increase in m6A modification. Furthermore, Alkbh5 KO mice exhibited reduced RVSP, RV/(LV + S), and attenuated vascular remodeling in HPH mice. Mechanistically, loss of Alkbh5 inhibited Cyp1a1 mRNA decay and increased its expression through an m6A-dependent post-transcriptional mechanism, which hindered the proliferation and migration of hypoxic PASMCs. CONCLUSION: The current study highlights the loss of Alkbh5 impedes the proliferation and migration of PASMCs by inhibiting post-transcriptional Cyp1a1 mRNA decay in an m6A-dependent manner.

Low-background interference detection of glyphosate, glufosinate, and AMPA in foods using UPLC-MS/MS without derivatization.

The abuse of herbicides has emerged as a great threat to food security. Herein, a low-background interference detection method based on UPLC-MS was developed for the simultaneous determination of glufosinate, glyphosate, and its metabolite aminomethylphosphonic acid (AMPA) in foods. Initially, this study proposed a simple and rapid pretreatment method, utilizing water extraction and PRiME HLB purification to isolate glyphosate, glufosinate, and AMPA from food samples. After the optimization of pretreatment conditions, the processed samples are then analyzed directly by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) without pre-column derivatization. The method can effectively reduce interference from by-products of pre-column derivatization and background substrates of food sample, showing low matrix effects (ME) ranging from - 24.83 to 32.10%. Subsequently, the method has been validated by 13 kinds of food samples. The recoveries of the three herbicides in the food samples range from 84.2 to 115.6%. The limit of detection (LOD) is lower to 0.073 mg/kg, 0.017 mg/kg, and 0.037 mg/kg, respectively. Moreover, the method shows an excellent reproducibility with relative standard deviations (RSD) within 16.9%. Thus, the method can provide high trueness, reproducibility, sensitivity, and interference-free detection to ensure human health safety.

Prevalence and Residual Risk of HIV in Volunteer Blood Donors of Zhejiang Province, China, from 2018 to 2022.

Background: Blood safety levels have been significantly improved since the implementation of nucleic acid amplification technology (NAT) testing for blood donors. However, there remains a residual risk of transfusion transmission infections. This study aimed to evaluate the prevalence of HIV and its residual risk transmission among volunteer blood donors of Zhejiang Province, China, for five years after NAT implementation. Materials and Methods: All specimens and information were collected from voluntary unpaid donors at all blood services in Zhejiang Province, China, from January 2018 to December 2022. The HIV antibody or antigen and HIV RNA were detected using enzyme-linked immunosorbent assay and NAT, respectively. The HIV residual risk transmission was calculated using the incidence or window period model. Results: A total of 3,375,678 voluntary blood donors were detected, revealing an HIV prevalence of 9.92/100000. The HIV prevalence of blood donors in 12 blood services in Zhejiang Province was 6.11, 6.98, 7.45, 8.21, 8.36, 8.94, 9.04, 9.66, 9.73, 10.22, 11.80, and 12.47 per 100000 donors, without statistically significant difference observed among the services (p > 0.05). The HIV prevalence of males (15.49/100000) was significantly higher compared to females (1.95/100000; p < 0.05). There was an insignificant difference in HIV prevalence among blood donors of all different age groups (p > 0.05), but the HIV prevalence in the 26-35 age group and 18-25 age group was significantly higher compared to the 36-45 age group (p < 0.05). The difference in HIV prevalence between first-time blood donors (13.65/100,000) and repeat blood donors (6.78/100,000) was statistically significant (p < 0.05). From 2018 to 2022, the HIV residual risk in blood transfusion transmission was 0.266/100000. Conclusion: The prevalence of HIV among blood donors in Zhejiang Province, China, is associated with age, gender, and times of blood donation. The HIV residual risk in blood transfusion transmission remains low in the province, and increasing the rate of repeat blood donors is beneficial to improve blood safety.

Neurovascular coupling in the attention during visual working memory processes.

Focusing attention in visual working memory (vWM) depends on the ability to filter distractors and expand the scope of targets. Although many properties of attention processes in vWM have been well documented, it remains unclear how the mechanisms of neurovascular coupling (NVC) function during attention processes in vWM. Here, we show simultaneous multimodal data that reveal the similar temporal and spatial features of attention processes during vWM. These similarities lead to common NVC outcomes across individuals. When filtering out distractors, the electroencephalography (EEG)-informed NVC displayed broader engagement across the frontoparietal network. A negative correlation may exist between behavioral metrics and EEG-informed NVC strength related to attention control. On a dynamic basis, NVC features exhibited higher discriminatory power in predicting behavior than other features alone. These results underscore how multimodal approaches can advance our understanding of the role of attention in vWM, and how NVC fluctuations are associated with actual behavior.

Axonopathy Underlying Amyotrophic Lateral Sclerosis: Unraveling Complex Pathways and Therapeutic Insights.

Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by progressive axonopathy, jointly leading to the dying back of the motor neuron, disrupting both nerve signaling and motor control. In this review, we highlight the roles of axonopathy in ALS progression, driven by the interplay of multiple factors including defective trafficking machinery, protein aggregation, and mitochondrial dysfunction. Dysfunctional intracellular transport, caused by disruptions in microtubules, molecular motors, and adaptors, has been identified as a key contributor to disease progression. Aberrant protein aggregation involving TDP-43, FUS, SOD1, and dipeptide repeat proteins further amplifies neuronal toxicity. Mitochondrial defects lead to ATP depletion, oxidative stress, and Ca2+ imbalance, which are regarded as key factors underlying the loss of neuromuscular junctions and axonopathy. Mitigating these defects through interventions including neurotrophic treatments offers therapeutic potential. Collaborative research efforts aim to unravel ALS complexities, opening avenues for holistic interventions that target diverse pathological mechanisms.

Coronary slow flow and angiography-derived index of microcirculatory resistance as prognostic predictors in patients with angina and normal coronary arteries: a retrospective cohort study.

BACKGROUND: This study aims to investigate prognostic implications of coronary slow flow (CSF) and angiography-derived index of microcirculatory resistance (caIMR) in patients with angina and normal coronary arteries. METHODS: A total of 582 patients were enrolled with angiographically normal coronary arteries. caIMR was calculated using a commercial software. Patients were followed up for a median of 45 months. The primary endpoint was defined as major adverse cardiovascular events (MACEs) comprising death, myocardial infarction and readmission for angina or heart failure. RESULTS: CSF was diagnosed when TIMI grade 2 flow presented in at least one coronary artery. Multivariate analysis indicated TIMI-flow-based determination of CSF was not significantly associated with MACEs [hazard ratio (HR): 2.14; 95% confidence interval (CI): 0.87-5.31; p = 0.099), while caIMR >42 (HR: 2.53; 95% CI: 1.02-6.32; p = 0.047) were independent predictors of MACEs. Incorporation of caIMR improved the area under the curve from 0.587 to 0.642. CONCLUSIONS: caIMR was an independent prognostic factor of long-term cardiovascular events in patients with CSF. Evaluation of caIMR improved the risk stratification of patients with angiographically-normal coronary arteries.

Actomyosin-II protects axons from degeneration induced by mild mechanical stress.

Whether, to what extent, and how the axons in the central nervous system (CNS) can withstand sudden mechanical impacts remain unclear. By using a microfluidic device to apply controlled transverse mechanical stress to axons, we determined the stress levels that most axons can withstand and explored their instant responses at nanoscale resolution. We found mild stress triggers a highly reversible, rapid axon beading response, driven by actomyosin-II-dependent dynamic diameter modulations. This mechanism contributes to hindering the long-range spread of stress-induced Ca2+ elevations into non-stressed neuronal regions. Through pharmacological and molecular manipulations in vitro, we found that actomyosin-II inactivation diminishes the reversible beading process, fostering progressive Ca2+ spreading and thereby increasing acute axonal degeneration in stressed axons. Conversely, upregulating actomyosin-II activity prevents the progression of initial injury, protecting stressed axons from acute degeneration both in vitro and in vivo. Our study unveils the periodic actomyosin-II in axon shafts cortex as a novel protective mechanism, shielding neurons from detrimental effects caused by mechanical stress.