Precise prediction of cerebrospinal fluid amyloid beta protein for early Alzheimer's disease detection using multimodal data.

Alzheimer's disease (AD) constitutes a neurodegenerative disorder marked by a progressive decline in cognitive function and memory capacity. The accurate diagnosis of this condition predominantly relies on cerebrospinal fluid (CSF) markers, notwithstanding the associated burdens of pain and substantial financial costs endured by patients. This study encompasses subjects exhibiting varying degrees of cognitive impairment, encompassing individuals with subjective cognitive decline, mild cognitive impairment, and dementia, constituting a total sample size of 82 participants. The primary objective of this investigation is to explore the relationships among brain atrophy measurements derived from magnetic resonance imaging, atypical electroencephalography (EEG) patterns, behavioral assessment scales, and amyloid ß-protein (Aß) indicators. The findings of this research reveal that individuals displaying reduced Aß1-42/Aß-40 levels exhibit significant atrophy in the frontotemporal lobe, alongside irregularities in various parameters related to EEG frequency characteristics, signal complexity, inter-regional information exchange, and microstates. The study additionally endeavors to estimate Aß1-42/Aß-40 content through the application of a random forest algorithm, amalgamating structural data, electrophysiological features, and clinical scales, achieving a remarkable predictive precision of 91.6%. In summary, this study proposes a cost-effective methodology for acquiring CSF markers, thereby offering a valuable tool for the early detection of AD.

Mechanisms of action of Shizhenqing granules for eczema treatment: Network pharmacology analysis and experimental validation.

Background: Jiuwan decoction has been used to treat chronic eczema since the Qing Dynasty. According to clinical experience, Shizhenqing granules (SZQG), derived from the Jiuwan decoction, exert beneficial clinical effects on acute eczema and reduce recurrence. Therefore, we elucidated the underlying mechanisms of SZQG through network pharmacology, molecular docking, and experimental validation. Methods: The main chemical components of SZQG were identified by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). And the targets of SZQG against eczema were screened out through online databases. Then, the regulatory network map of the "herbal compound-potential target" and the target protein-protein interaction (PPI) network was constructed. The Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using by R language. Additionally, the interaction between the active compounds and the targets was verified by molecular docking technology. Finally, an experiment in vivo was used to verify the effect and mechanism of SZQG on eczema. Results: Using UHPLC-MS/MS, 158 main chemical compounds of SZQG were identified, and 72 compounds were selected according to the criteria for further analysis. All 237 potential targets of SZQG in eczema were explored using multiple online databases. The network with 14 core targets was screened out, including STAT3, RELA, TNF, JUN, MAPK3, IL-6, PIK3CA, STAT1, MAPK14, MAPK1, IL-4, NFKBIA, IL1B, and MYC. KEGG analyses indicated that the therapeutic effects of SZQG on eczema were predominantly associated with cytokine-cytokine receptor interaction, TNF, MAPK, NF-κB, toll-like receptor, T cell receptor, and Th1 and Th2 cell differentiation signaling pathways. Furthermore, the good affinity between the core compounds and core targets was verified by molecular docking technology, particularly for RELA and MAPK. Animal experiments revealed that SZQG downregulated MAPK14, RELA, T-bet, and GATA3 mRNA expression, reduced immunoglobulin E (IgE) and interleukin-4 (IL-4) serum concentrations, and improved eczema-like lesions in model rats. Conclusion: This study identified potential targets and signaling pathways of SZQG in the treatment of eczema, whereby RELA and MAPK14 may constitute the main therapeutic targets of SZQG in cytokine regulation and reduction of inflammatory responses.

An ensemble learning model for continuous cognition assessment based on resting-state EEG.

One critical manifestation of neurological deterioration is the sign of cognitive decline. Causes of cognitive decline include but are not limited to: aging, cerebrovascular disease, Alzheimer's disease, and trauma. Currently, the primary tool used to examine cognitive decline is scale. However, scale examination has drawbacks such as its clinician subjectivity and inconsistent results. This study attempted to use resting-state EEG to construct a cognitive assessment model that is capable of providing a more scientific and robust evaluation on cognition levels. In this study, 75 healthy subjects, 99 patients with Mild Cognitive Impairment (MCI), and 78 patients with dementia were involved. Their resting-state EEG signals were collected twice, and the recording devices varied. By matching these EEG and traditional scale results, the proposed cognition assessment model was trained based on Adaptive Boosting (AdaBoost) and Support Vector Machines (SVM) methods, mapping subjects' cognitive levels to a 0-100 test score with a mean error of 4.82 (<5%). This study is the first to establish a continuous evaluation model of cognitive decline on a large sample dataset. Its cross-device usability also suggests universality and robustness of this EEG model, offering a more reliable and affordable way to assess cognitive decline for clinical diagnosis and treatment as well. Furthermore, the interpretability of features involved may further contribute to the early diagnosis and superior treatment evaluation of Alzheimer's disease.

A Real-Time Non-Implantation Bi-Directional Brain-Computer Interface Solution Without Stimulation Artifacts.

The non-implantation bi-directional brain-computer interface (BCI) is a neural interface technology that enables direct two-way communication between the brain and the external world by both "reading" neural signals and "writing" stimulation patterns to the brain. This technology has vast potential applications, such as improving the quality of life for individuals with neurological and mental illnesses and even expanding the boundaries of human capabilities. Nonetheless, non-implantation bi-directional BCIs face challenges in generating real-time feedback and achieving compatibility between stimulation and recording. These issues arise due to the considerable overlap between electrical stimulation frequencies and electrophysiological recording frequencies, as well as the impediment caused by the skull to the interaction of external and internal currents. To address those challenges, this work proposes a novel solution that combines the temporal interference stimulation paradigm and minimally invasive skull modification. A longitudinal animal experiment has preliminarily validated the feasibility of the proposed method. In signal recording experiments, the average impedance of our scheme decreased by 4.59 kΩ , about 67%, compared to the conventional technique at 18 points. The peak-to-peak value of the Somatosensory Evoked Potential increased by 8%. Meanwhile, the signal-to-noise ratio of Steady-State Visual Evoked Potential increased by 5.13 dB, and its classification accuracy increased by 44%. The maximum bandwidth of the resting state rose by 63%. In electrical stimulation experiments, the signal-to-noise ratio of the low-frequency response evoked by our scheme rose by 8.04 dB, and no stimulation artifacts were generated. The experimental results show that signal quality in acquisition has significantly improved, and frequency-band isolation eliminates stimulation artifacts at the source. The acquisition and stimulation pathways are real-time compatible in this non-implantation bi-directional BCI solution, which can provide technical support and theoretical guidance for creating closed-loop adaptive systems coupled with particular application scenarios in the future.

Arbitrarily rotated optical axis waveguide induced by a trimming line.

Rotated optical axis waveguides can facilitate on-chip arbitrary wave-plate operations, which are crucial tools for developing integrated universal quantum computing algorithms. In this paper, we propose a unique technique based on femtosecond laser direct writing technology to fabricate arbitrarily rotated optical axis waveguides. First, a circular isotropic main waveguide with a non-optical axis was fabricated using a beam shaping method. Thereafter, a trimming line was used to create an artificial stress field near the main waveguide to induce a rotated optical axis. Using this technique, we fabricated high-performance half- and quarter-wave plates. Subsequently, high-fidelity (97.1%) Pauli-X gate operation was demonstrated via quantum process tomography, which constitutes the basis for the full manipulation of on-chip polarization-encoded qubits. In the future, this work is expected to lead to new prospects for polarization-encoded information in photonic integrated circuits.

Analysis of the prevalence and influencing factors of anxiety and depression in the Chinese population: A cross-sectional survey.

To explore the prevalence and influencing factors of anxiety and depression symptoms among Chinese people in 2021. Investigation teams were recruited in 120 cities across the country. Based on the data from "the Seventh National Population Census in 2021″, quota sampling was conducted on the residents of these cities to obtain samples that conformed to population characteristics. Next, baseline information on research objects was collected, and the questionnaire survey was conducted through the online questionnaire Wenjuanxing platform. The Patient Health Questionnaire-9 (PHQ-9) rating scale was used to evaluate the mental state of the subjects. The correlation between baseline information and different PHQ-9 risk intervals was analyzed using the Chi-square test and Logit model. The impact of relevant risk factors on PHQ-9 scores was analyzed using the decision tree. The Chi-square test results revealed that place of residence (p = 0.438) and obesity (p = 0.443) was not significantly correlated with PHQ-9 risk intervals. According to Logit model analysis, age (p = 0.001, 95%CI 0.84-0.96), marital status (p < 0.001, 95%CI 0.71-0.89), drinking (p < 0.001, 95%CI 1.07-1.18), diabetes or hypertension (p = 0.001, 95%CI 1.11-1.47), health care (p < 0.001, 95%CI 0.53-0.66), economic welfare (p = 0.022, 95%CI 0.85-0.99), COVID-19 vaccine (p < 0.001, 95%CI 1.28-1.72), and HPV vaccine (p < 0.001, 95%CI 0.46-0.57) were potential influencing factors of PHQ-9 risk intervals. Decision tree analysis results showed that the grouping strategy in the PHQ-9 two-side groups had a better classification effect on the questionnaire population according to the PHQ-9 score characteristics. The prevalence rate of moderate to severe depression among Chinese people was about 8.29%. Age, marital status, drinking, diabetes or hypertension, health care, economic well, COVID-19 vaccine, and HPV vaccine were potential influencing factors of anxiety and depression symptoms in Chinese people.

Seasonal differences in intestinal flora are related to rats' intestinal water metabolism.

Many studies have reported obvious seasonal differences in the intestinal flora of rats, and this stable distribution of the seasonal flora helps in maintaining the normal physiological function of the host. However, the mechanism underlying these seasonal differences in intestinal flora remains unclear. To explore the correlation among seasonal factors and intestinal water metabolism and intestinal flora, 20 Sprague Dawley (SD) rats were divided into spring, summer, autumn, and winter groups. The environment for the four seasons was simulated using the Balanced Temperature and Humidity Control system. The intestinal water metabolism was evaluated by determining the intestinal transmission function, fecal water content, water content of colonic tissue, and the colonic expression levels of AQP3, AQP4, and AQP8. The composition and relative abundance of intestinal microflora in rats in each season were assessed through 16S rDNA amplifier sequencing, and the relationship between the dominant flora and intestinal water metabolism in each season was analyzed using Spearman correlation analysis. The high temperature and humidity season could lead to an increase in intestinal water metabolism and intestinal water content in rats, whereas the low temperature and humidity season could lead to a decrease, which was closely related to the change in microflora. To explore the molecular mechanism of seasonal changes in intestinal water metabolism, the concentration of colonic 5-HT, VIP, cAMP, and PKA associated with intestinal water metabolism in rats were also examined. Seasonal changes could affect the concentration of colonic 5-HT and VIP in rats, and then regulate AQPs through cAMP/PKA pathway to affect the intestinal water metabolism. These results suggest that seasonal factors affect the level of intestinal water metabolism in rats and result in seasonal differences in intestinal flora.

Reliability and validity of the Chinese version of the Sakata Eating Behavior Scale short form and preliminary analysis of the factors related to the score of the scale.

Background: The obesity rate in the Chinese population is increasing and there is a lack of short and reliable scales for measuring obesity-related eating behavior in China. The EBS-SF (Sakata Eating Behavior Scale short form) has only 7 entries and has shown good reliability in studies such as those in Japan. Objective: To translate the EBS-SF into Chinese, check its reliability, validity and explore the related factors. Method: The EBS-SF was translated into Chinese. 3,440 residents were investigated and 34 respondents were retested. Item analysis and reliability and validity tests were carried out. Personality characteristics, family health status and depression were investigated using the BFI-10, FHS-SF and PHQ-9 to investigate the factors associated with EBS-SF. The t-test, ANOVA and Pearson correlation was used to explore the related factors of its scores. Result: Among 3,440 residents, 1,748 (50.81%) were male and 1,692 (49.19%) were female; 1,373 (39.91%) were aged 36-50 years. All 7 items were qualified in the item analysis. As for reliability, the Cronbach's α was 0.870, the split-half reliability was 0.830, the test-retest correlation coefficient was 0.868. As for the structural validity, the standardized factor loadings were above 0.50, χ2 / df = 2.081,GFI = 0.999; NFI = 0.999; RFI = 0.996; RMSEA = 0.018, all qualified. The characteristics, personality, family health and depression were correlated with the score of the Chinese version of EBS short form. Conclusion: The structural validity and reliability of the Chinese version of the EBS-SF are good and it can be used as a measurement tool to evaluate the eating behavior of Chinese. The scores of the EBS-SF may be related to the sociological characteristics, personality, family health, and depression status.

A Binocular Vision SSVEP Brain-Computer Interface Paradigm for Dual-Frequency Modulation.

OBJECTIVE: This study presents a novel brain-computer interface paradigm of dual-frequency modulated steady-state visual evoked potential (SSVEP), aiming to suppress the unpredictable intermodulation components in current applications. This paradigm is especially suitable for training-free scenarios. APPROACH: This study built a dual-frequency binocular vision SSVEP brain-computer interface system using circularly polarized light technology. Two experiments, including a 6-target offline experiment and a 40-target online experiment, were taken with this system. Meanwhile, an improved algorithm filter bank dual-frequency canonical correlation analysis (FBDCCA) was presented for the dual-frequency SSVEP paradigm. MAIN RESULTS: Energy analysis was conducted for 9 subjects in the 6-target dual-frequency offline experiment, among which the signal-to-noise ratio of target frequency components have increased by 2 dB compared to the one of unpredictable intermodulation components. Subsequently, the online experiment with 40 targets was conducted with 12 subjects. With this new dual-frequency paradigm, the online training-free experiment's average information transmission rate (ITR) reached 104.56 ± 15.74 bits/min, which was almost twice as fast as the current best dual-frequency paradigm. And the average information transfer rate for offline training analysis of this new paradigm was 180.87 ± 17.88 bits/min. SIGNIFICANCE: These results demonstrate that this new dual-frequency SSVEP brain-computer interface paradigm can suppress the unpredictable intermodulation harmonics and generate higher quality responses while completing dual-frequency encoding. Moreover, its performance shows high ITR in applications both with and without training. It is thus believed that this paradigm is competent for achieving large target numbers in brain-computer interface systems and has more possible practices.

Minimally Invasive Local-Skull Electrophysiological Modification With Piezoelectric Drill.

The research on non-invasive BCI is nowadays hitting the bottleneck due to the humble quality of scalp EEG signals. Whereas invasive solutions that offer higher signal quality in contrast are suffocated in their spreading because of the potential surgical complication and health risks caused by electrode implantation. Therefore, it puts forward a necessity to explore a scheme that could both collect high-quality EEG signals and guarantee high-level operation safety.This study proposed a Minimally Invasive Local-skull Electrophysiological Modification method to improve scalp EEG signals qualities at specific brain regions. Six eight-month-old SD rats were used for in vivo verification experiment. A hole with a diameter of about 500 micrometers was drilled in the skull above the visual cortex of rats. Significant changes in rsEEG and SSVEP signals before and after modification were observed. After modification, the skull impedance of rats decreases by about 84 %, the average maximum bandwidth of rsEEG increase by 57 %, and the broadband SNR of SSVEP is increased by 5.13 dB. The time of piezoelectric drilling operation is strictly controlled under 30 seconds for each rat to prevent possible brain damage from overheating. Compared with traditional invasive procedures such as ECoG, Minimally Invasive Local-skull Electrophysiological Modification operation time is shorter and no electrode implantation is needed while it remarkably boosts the scalp EEG signal quality. This technical solution has the potential to replace the use of ECoG in certain application scenarios and further invigorate studies in the field of scalp EEG in the future.

Ferroptosis is essential for diabetic cardiomyopathy and is prevented by sulforaphane via AMPK/NRF2 pathways.

Herein, we define the role of ferroptosis in the pathogenesis of diabetic cardiomyopathy (DCM) by examining the expression of key regulators of ferroptosis in mice with DCM and a new ex vivo DCM model. Advanced glycation end-products (AGEs), an important pathogenic factor of DCM, were found to induce ferroptosis in engineered cardiac tissues (ECTs), as reflected through increased levels of Ptgs2 and lipid peroxides and decreased ferritin and SLC7A11 levels. Typical morphological changes of ferroptosis in cardiomyocytes were observed using transmission electron microscopy. Inhibition of ferroptosis with ferrostatin-1 and deferoxamine prevented AGE-induced ECT remodeling and dysfunction. Ferroptosis was also evidenced in the heart of type 2 diabetic mice with DCM. Inhibition of ferroptosis by liproxstatin-1 prevented the development of diastolic dysfunction at 3 months after the onset of diabetes. Nuclear factor erythroid 2-related factor 2 (NRF2) activated by sulforaphane inhibited cardiac cell ferroptosis in both AGE-treated ECTs and hearts of DCM mice by upregulating ferritin and SLC7A11 levels. The protective effect of sulforaphane on ferroptosis was AMP-activated protein kinase (AMPK)-dependent. These findings suggest that ferroptosis plays an essential role in the pathogenesis of DCM; sulforaphane prevents ferroptosis and associated pathogenesis via AMPK-mediated NRF2 activation. This suggests a feasible therapeutic approach with sulforaphane to clinically prevent ferroptosis and DCM.

Latest Effective Measures to Combat COVID-19: A Review.

More and more people realize that implementation of preventive measures is the only option left to counteract the coronavirus disease 2019 (COVID-19) before specific antiviral drugs are developed. Hence, a number of behavioral, clinical and state interventions have been conducted by dozens of countries to stop or slow down the spread of the virus in the early stages of the epidemic. At present, with the evolution of COVID-19 pandemic getting worse, synthesizing and implementing all measures available are of paramount importance. However, some measures are still being controversial. We aimed to assist policymakers in decision making for better pandemic preparedness. We reviewed the literature that reported accumulated scientific experience to date and summarized the epidemic prevention and control measures in three aspects: control the source of infection, cut off the routes of transmission and protect the susceptible population. First of all, some new approaches were introduced to control the source of infection, such as implementing contact-tracing apps, nucleic acid mixed detection, repeated testing and the establishment of some specialized laboratories. Second, we need to take various measures to cut off all possible routes of transmission, especially persistently pay close attention to checking cold chain foods. Third, due to no valid vaccine has yet been developed, some measures that can cut development time of more conventional vaccines should be implemented or considered. By synthesizing the scientific experience in fighting the COVID-19 epidemic, we suggested the latest effective measures should be carried out concurrently from three aspects, so as to avoid making grim situation even worse.

Protective effects of sulforaphane on type 2 diabetes-induced cardiomyopathy via AMPK-mediated activation of lipid metabolic pathways and NRF2 function.

BACKGROUND: AMP-activated protein kinase (AMPK), particularly AMPKα2 isoform, plays a critical role in maintaining cardiac homeostasis. It was reported that sulforaphane (SFN) prevented type 2 diabetes (T2D)-induced cardiomyopathy accompanied by the activation of AMPK; In this study, AMPK's pivotal role in SFN-mediated prevention against T2D-induced cardiomyopathy was tested using global deletion of AMPKα2 gene (AMPKα2-KO) mice. METHODS AND RESULTS: T2D was established by feeding 3-month high-fat diet (HFD) to induce insulin resistance, followed by an intraperitoneal injection of streptozotocin (STZ) to induce mild hyperglycemia in both AMPKα2-KO and wild-type (WT) mice. Then both T2D and control mice were subsequently treated with or without SFN for 3 months while continually feeding HFD or normal diet. Upon completion of the 3-month treatment, five mice from each group were sacrificed as a 3-month time-point (3 M). The rest continued normal diet or HFD until terminating study at the sixth month (6 M) of diabetes. Cardiac function was examined with echocardiography before sacrifice at both 3 M and 6 M. SFN prevented T2D-induced progression of cardiac dysfunction, remodeling (hypertrophy and fibrosis), inflammation, and oxidative damage in wild-type diabetic mice, but not in AMPKα2-KO mice. Mechanistically, SFN prevented T2D-induced cardiomyopathy not only by improving AMPK-mediated lipid metabolic pathways, but also enhancing NRF2 activation via AMPK/AKT/GSK3ß pathway. However, these improving effects of SFN were abolished in AMPKα2-KO diabetic mice. CONCLUSIONS: AMPK is indispensable for the SFN-induced prevention of cardiomyopathy in T2D, and the activation of NRF2 by SFN is mediated by AMPK/AKT/GSK3ß signaling pathways.

Femtosecond laser self-assembly for silver vanadium oxide flower structures.

Flower-like silver vanadium oxide (SVO) micropatterns were realized by femtosecond laser in situ writing from its precursor. Self-assembled petals irradiated by a femtosecond laser were observed standing on the substrate along the scanned routine assisted by the formation of silver seeds and plasmonic-mediated effects. By controlling the concentration of ammonium monovanadate and the laser exposure time, a different thickness of petals was manipulated from ∼100 nm to micrometers. The SVO products were confirmed Ag4V2O7, AgVO3, and part of Ag3VO4 by x-ray diffraction (XRD) measurement. Photon-driven self-assembly for in situ fabrication of microstructures looks to be an effective and facile technique for SVO and other functional compounds.

Plasmonic nano-imprinting by photo-doping.

A method to directly explore the effect of electron density on the surface plasmon wave and the corresponding laser-induced structures is demonstrated by controllable doping of silver nitrate (AgNO3) into a water-soluble polymer polyvinyl alcohol (PVA). It is shown that periodic nanostructures on PVA appeared only when the electron density was more than 6×1020 cm-3 and became uniform when doping density corresponded to 1.2×1021 cm-3. Photo-excitation of electrons in the Ag-doped PVA defined by laser fluence determined the conditions of surface plasmon wave and formation of nanostructures on the surface. The Drude-Lorentz model was used to describe the formation conditions of surface wave and to estimate the period of the structures. The demonstrated photo-electron doping brings required means to control the formation of laser-induced patterns with an optical sub-wavelength resolution.

Mirror-rotation-symmetrical single-focus spiral zone plates.

In this Letter, we report mirror-rotation-symmetrical single-focus spiral zone plates (MS-SZPs) fabricated by femtosecond laser direct writing. The novel optical element can generate a single-focus vortex beam, owing to the element's complicated continuous surface. The MS-SZP surface possesses reverse mirror-rotation symmetry, which ensures that the transfer element has the same surface morphology as the original element. Both the transfer element and original element have good optical properties. The single-focus behavior was investigated by a microscopic imaging system and found to be in good agreement with theoretical simulation results. The innovative optical component is expected to be widely used in optical communication, quantum computation, optical manipulation, and other fields.