The receptor binding domain of SARS-CoV-2 Omicron subvariants targets Siglec-9 to decrease its immunogenicity by preventing macrophage phagocytosis.

The development of a vaccine specific to severe acute respiratory syndrome coronavirus 2 Omicron has been hampered due to its low immunogenicity. Here, using reverse mutagenesis, we found that a phenylalanine-to-serine mutation at position 375 (F375S) in the spike protein of Omicron to revert it to the sequence found in Delta and other ancestral strains significantly enhanced the immunogenicity of Omicron vaccines. Sequence FAPFFAF at position 371-377 in Omicron spike had a potent inhibitory effect on macrophage uptake of receptor-binding domain (RBD) nanoparticles or spike-pseudovirus particles containing this sequence. Omicron RBD enhanced binding to Siglec-9 on macrophages to impair phagocytosis and antigen presentation and promote immune evasion, which could be abrogated by the F375S mutation. A bivalent F375S Omicron RBD and Delta-RBD nanoparticle vaccine elicited potent and broad nAbs in mice, rabbits and rhesus macaques. Our research suggested that manipulation of the Siglec-9 pathway could be a promising approach to enhance vaccine response.

Surface-based morphometry of the corpus callosum in young children of ages 1-5.

The corpus callosum (CC) is a large white matter fiber bundle in the brain and is involved in various cognitive, sensory, and motor processes. While implicated in various developmental and psychiatric disorders, much is yet to be uncovered about the normal development of this structure, especially in young children. Additionally, while sexual dimorphism has been reported in prior literature, observations have not necessarily been consistent. In this study, we use morphometric measures including surface tensor-based morphometry (TBM) to investigate local changes in the shape of the CC in children between the ages of 12 and 60 months, in intervals of 12 months. We also analyze sex differences in each of these age groups. We observed larger significant clusters in the earlier ages between 12 v 24 m and between 48 v 60 m and localized differences in the anterior region of the body of the CC. Sex differences were most pronounced in the 12 m group. This study adds to the growing literature of work aiming to understand the developing brain and emphasizes the utility of surface TBM as a useful tool for analyzing regional differences in neuroanatomical morphometry.

Effects of the alpine meadow in different phenological periods on rumen fermentation and gastrointestinal tract bacteria community in grazing yak on the Qinghai-Tibetan Plateau.

BACKGROUND: In this study, we investigated the effects of alpine meadow in different phenological periods on ruminal fermentation, serum biochemical indices, and gastrointestinal tract microbes in grazing yak on the Qinghai-Tibetan Plateau. A total of eighteen female freely grazing yaks with an average age of 3 years old and a body weight of 130 ± 19 kg were selected. According to the plant phenological periods, yaks were randomly allocated to one of three treatments: (1) regreen periods group (RP, n = 6); (2) grassy periods group (GP, n = 6); and (3) hay periods group (HP, n = 6). At the end of the experiment, the blood, rumen fluids, and rectal contents were collected to perform further analysis. RESULTS: The concentrations of total volatile fatty acid (TVFA), acetate, glucose (GLU), triglyceride (TG), cholesterol (CHO), high density lipoprotein (HDL), and low density lipoprotein (LDL) were higher in the GP group than in the HP group (P < 0.05). However, compared with the RP and GP groups, the HP group had higher concentrations of isobutyrate, isovalerate, valerate, and creatinine (CREA) (P < 0.05). The abundance of Prevotella in the rumen, and the abundances of Rikenellaceae_RC9_gut_group, Eubacterium_coprostanoligenes_group, and Prevotellaceae_UCG-004 in the gut were higher in the GP group compared with the HP group (P < 0.05). The HP had higher abundance of Eubacterium_coprostanoligenes_group in the rumen as well as the abundances of Romboutsia and Arthrobacter in the gut compared with the RP and GP groups (P < 0.05). CONCLUSIONS: Based on the results of rumen fermentation, serum biochemical, differential biomarkers, and function prediction, the carbohydrate digestion of grazing yak would be higher with the alpine meadow regreen and grassy due to the gastrointestinal tract microbes. However, the risk of microbe disorders and host inflammation in grazing yak were higher with the alpine meadow wither.

Bacteria-Like Gaiella Accelerate Soil Carbon Loss by Decomposing Organic Matter of Grazing Soils in Alpine Meadows on the Qinghai-Tibet Plateau.

The alpine meadows of the Qinghai-Tibet Plateau have significant potential for storing soil carbon, which is important to global carbon sequestration. Grazing is a major threat to its potential for carbon sequestration. However, grazing poses a major threat to this potential by speeding up the breakdown of organic matter in the soil and releasing carbon, which may further lead to positive carbon-climate change feedback and threaten ecological security. Therefore, in order to accurately explore the driving mechanism and regulatory factors of soil organic matter decomposition in grazing alpine meadows on the Qinghai-Tibet Plateau, we took the grazing sample plots of typical alpine meadows as the research object and set up grazing intensities of different life cycles, aiming to explore the relationship and main regulatory factors of grazing on soil organic matter decomposition and soil microorganisms. The results show the following: (1) soil microorganisms, especially Acidobacteria and Acidobacteria, drove the decomposition of organic matter in the soil, thereby accelerating the release of soil carbon, which was not conducive to soil carbon sequestration in grassland; (2) the grazing triggering effect formed a positive feedback with soil microbial carbon release, accelerating the decomposition of organic matter and soil carbon loss; and (3) the grazing ban and light grazing were more conducive to slowing down soil organic matter decomposition and increasing soil carbon sequestration.

Renal interstitial fibrotic assessment using non-Gaussian diffusion kurtosis imaging in a rat model of hyperuricemia.

BACKGROUND: To investigate the feasibility of Diffusion Kurtosis Imaging (DKI) in assessing renal interstitial fibrosis induced by hyperuricemia. METHODS: A hyperuricemia rat model was established, and the rats were randomly split into the hyperuricemia (HUA), allopurinol (AP), and AP + empagliflozin (AP + EM) groups (n = 19 per group). Also, the normal rats were selected as controls (CON, n = 19). DKI was performed before treatment (baseline) and on days 1, 3, 5, 7, and 9 days after treatment. The DKI indicators, including mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) of the cortex (CO), outer stripe of the outer medulla (OS), and inner stripe of the outer medulla (IS) were acquired. Additionally, hematoxylin and eosin (H&E) staining, Masson trichrome staining, and nuclear factor kappa B (NF-κB) immunostaining were used to reveal renal histopathological changes at baseline, 1, 5, and 9 days after treatment. RESULTS: The HUA, AP, and AP + EM group MKOS and MKIS values gradually increased during this study. The HUA group exhibited the highest MK value in outer medulla. Except for the CON group, all the groups showed a decreasing trend in the FA and MD values of outer medulla. The HUA group exhibited the lowest FA and MD values. The MKOS and MKIS values were positively correlated with Masson's trichrome staining results (r = 0.687, P < 0.001 and r = 0.604, P = 0.001, respectively). The MDOS and FAIS were negatively correlated with Masson's trichrome staining (r = -626, P < 0.0014 and r = -0.468, P = 0.01, respectively). CONCLUSION: DKI may be a non-invasive method for monitoring renal interstitial fibrosis induced by hyperuricemia.

Astaxanthin Inhibits H2O2-Induced Excessive Mitophagy and Apoptosis in SH-SY5Y Cells by Regulation of Akt/mTOR Activation.

Oxidative stress, which damages cellular components and causes mitochondrial dysfunction, occurs in a variety of human diseases, including neurological disorders. The clearance of damaged mitochondria via mitophagy maintains the normal function of mitochondria and facilitates cell survival. Astaxanthin is an antioxidant known to have neuroprotective effects, but the underlying mechanisms remain unclear. This study demonstrated that astaxanthin inhibited H2O2-induced apoptosis in SH-SY5Y cells by ameliorating mitochondrial damage and enhancing cell survival. H2O2 treatment significantly reduced the levels of activated Akt and mTOR and induced mitophagy, while pretreatment with astaxanthin prevented H2O2-induced inhibition of Akt and mTOR and attenuated H2O2-induced mitophagy. Moreover, the inhibition of Akt attenuated the protective effect of astaxanthin against H2O2-induced cytotoxicity. Taken together, astaxanthin might inhibit H2O2-induced apoptosis by protecting mitochondrial function and reducing mitophagy. The results also indicate that the Akt/mTOR signaling pathway was critical for the protection of astaxanthin against H2O2-induced cytotoxicity. The results from the present study suggest that astaxanthin can reduce neuronal oxidative injury and may have the potential to be used for preventing neurotoxicity associated with neurodegenerative diseases.

Analysis of the Therapeutic Efficacy of Hysteroscopic Electric Resection in the Treatment of Atypical Endometrial Hyperplasia and Factors Influencing Prognosis.

Objective: The objective of this study was to evaluate the efficacy of hysteroscopic electroresection in the treatment of atypical endometrial hyperplasia and to determine the prognostic factors. Methods: 226 patients with endometrial dysplasia treated in hospital from January 2021 to August 2022 were selected and divided into control group (113 cases) and study group (113 cases) according to different treatment methods selected by the patients themselves. The control group received curettage plus conventional progesterone treatment, while the study group received hysteroscopic electroresection plus conventional progesterone treatment. After 6 months of treatment, the clinical efficacy (complete response, partial response and progress) of the two groups were evaluated, complications and adverse drug reactions of the two groups were analyzed, and estrogen levels before and after treatment were compared between the two groups. After 1 year follow-up, patients were divided into relapse group and non-recurrence group according to whether they had relapse or not. Clinical data of the two groups were compared to analyze the related factors affecting the prognosis of patients. Results: (1) Chi-square test results showed that the total effective rate of the study group was higher (96.46% VS 77.88%) than that of the control group (P < .05). The complication rate and recurrence rate of the study group were lower than those of the control group (1.77% VS 7.96%, 4.42% VS 21.24%) (P < .05). (2) t test results of independent samples showed that after 6 months of treatment, the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the study group were lower than those in the control group (P < .05); (3) The t test results of independent samples indicated that the age and body mass index of the relapsed group were higher than those of the non-relapsed group (P < .05); Chi-square test results showed that the proportion of diabetes was higher than that of the group without recurrence, and the proportion of hysteroscopic electroresection was lower than that of the group without recurrence (P < .05). (4) Logistic regression model was established, and the results showed that age (OR=1.159), body mass index (OR=1.529) and diabetes (OR=3.861) were the risk factors for prognosis of patients with endometrial dysplasia (P < .05), and hysteroscopic electroresection was the protective factor (OR < 1, P < .05). Conclusion: Hysteroscopic electroresection shows significant potential in the treatment of atypical hyperplasia of endometrial, and can improve clinical efficacy and reduce complications by effectively regulating estrogen secretion. In addition, studies have shown that the prognosis of endometrial dysplasia may be related to the age of patients, body mass index and diabetes mellitus. Therefore, for patients with the above risk factors, early consideration of hysteroscopic electrotomy therapy is recommended to reduce recurrence rates and provide important informational support for treatment protocols and clinical guidelines.

Phosphorylation of ZmAL14 by ZmSnRK2.2 regulates drought resistance through derepressing ZmROP8 expression.

Drought stress has negative effects on crop growth and production. Characterization of transcription factors that regulate the expression of drought-responsive genes is critical for understanding the transcriptional regulatory networks in response to drought, which facilitates the improvement of crop drought tolerance. Here, we identified an Alfin-like (AL) family gene ZmAL14 that negatively regulates drought resistance. Overexpression of ZmAL14 exhibits susceptibility to drought while mutation of ZmAL14 enhances drought resistance. An abscisic acid (ABA)-activated protein kinase ZmSnRK2.2 interacts and phosphorylates ZmAL14 at T38 residue. Knockout of ZmSnRK2.2 gene decreases drought resistance of maize. A dehydration-induced Rho-like small guanosine triphosphatase gene ZmROP8 is directly targeted and repressed by ZmAL14. Phosphorylation of ZmAL14 by ZmSnRK2.2 prevents its binding to the ZmROP8 promoter, thereby releasing the repression of ZmROP8 transcription. Overexpression of ZmROP8 stimulates peroxidase activity and reduces hydrogen peroxide accumulation after drought treatment. Collectively, our study indicates that ZmAL14 is a negative regulator of drought resistance, which can be phosphorylated by ZmSnRK2.2 through the ABA signaling pathway, thus preventing its suppression on ZmROP8 transcription during drought stress response.

Dictyophora indusiata polysaccharide mediates priming of the NLRP3 inflammasome activation via TLR4/ NF-κB signaling pathway to exert immunostimulatory effects.

Dictyophora indusiata, commonly known as bamboo fungus, is a type of edible mushroom that is highly popular worldwide for its rich flavor and nutritional value. It is also recognized for its pharmaceutical efficacy, with medicinal benefits attributed to its consumption. One of the most important components of Dictyophora indusiata is polysaccharide, which has been acknowledged as a promising regulator of biological response due to its immunostimulatory and anti-inflammatory properties. However, the specific roles of polysaccharide in modulating the NOD-like receptor protein 3 (NLRP3) inflammasome activation within macrophages remain relatively under-researched. To investigate this further, the mechanism by which Dictyophora indusiata polysaccharide (DIP) exerts its immunostimulatory activity in RAW 264.7 macrophages was analyzed. Results indicated that DIP has the potential to facilitate the priming of NLRP3 inflammasome activation by enhancing TLR4 expression, phosphorylation of IκB-α, and nuclear translocation of NF-κB p65 subunit. It was noted that DIP was unable to mediate the second step of NLRP3 inflammasome activation. The findings of this study provide compelling evidence that DIP has immunomodulatory effects by modulating the NLRP3 inflammasome in RAW264.7 macrophages.

Corrigendum: How can the collaborative participation of regulators, whistleblowers, and parties effectively promote rumor management in public health emergencies?

[This corrects the article DOI: 10.3389/fpubh.2023.1290841.].

Adaptive smoothing of retinotopic maps based on Teichmüller parametrization.

Retinotopic mapping, the mapping between visual inputs on the retina and neural responses on the cortical surface, is one of the fundamental topics in visual neuroscience. In human studies, retinotopic maps are conventionally constructed and processed by decoding blood oxygenation-level dependent (BOLD) functional magnetic resonance imaging (fMRI) responses to designed visual stimuli on the cortical surface. However, these methods frequently generate retinotopic maps that do not preserve topology, contradicting a fundamental property of retinotopic maps observed in neurophysiology. To address this problem, we propose an integrated approach to simultaneously refine the flattening from the 3D cortical surface to the 2D parametric space and adaptively smooth retinotopic perception centers in the visual space to make the retinotopic maps topological. One key element of the approach is the enhanced error tolerant Teichmüller mapping, which refines the parametrization by minimizing angle distortions and maximizing alignment to noisy landmarks. We validated our overall approach with synthetic and real retinotopic mapping datasets and applied it to compute cortical magnification factor (CMF). The results showed that the proposed approach was superior to other conventional retinotopic mapping methods in predicting BOLD fMRI time series and preserving topology.

A Robust Causal Brain Network Measure and Its Application on Ictal Electrocorticogram Analysis of Drug-resistant Epilepsy.

Measuring causal brain network is a significant topic for exploring complex brain functions. While various data-driven algorithms have been proposed, they still have some drawbacks such as ignoring time non-separability, cumbersome parameter settings, and poor robustness. To solve these deficiencies, we developed a novel framework: "time-shift permutation cross-mapping, TPCM," integrating steps of (1) delayed improved phase-space reconstruction (DIPSR), (2) rank transformation of embedding vectors' distances, (3) cross-mapping with a fitting estimation, and (4) causality quantification using multi-delays. Based on synthetic models and comparison with baseline methods, numerical validation results demonstrate that TPCM significantly improves the robustness for data length with or without noise interference, and achieves the best quantification accuracy in detecting time delay and coupling strength, with the highest determination coefficient ( R2 = 0. 96 ) of fitting verse coupling parameters. The developed TPCM was finally applied to ictal electrocorticogram (ECoG) analysis of patients with drug-resistant epilepsy (DRE). A total of 17 patients with DRE were included into the retrospective study. For 8 patients undergoing successful surgeries, the causal coupling strength (0.58 ± 0.20) within epileptogenic zone network is significantly higher than those suffering failed surgeries (0.38 ± 0.16) with P < 0. 001 through Mann-Whitney-U-test. Therefore, the epileptic brain network measured by TPCM is a credible biomarker for predicting surgical outcomes. These findings additionally confirm TPCM's superior performance and promising potential to advance precision medicine for neurological disorders.

Dual-signal amplified electrochemical aptasensor based on Au/MrGO and DNA nanospheres for ultra-sensitive detection of BPA without directly modified working electrode.

Rapid and sensitive analysis of bisphenol A (BPA) is essential for preventing health risks to humans and animals. Hence, a signal-amplified electrochemical aptasensor without repetitive polishing and modification of working electrode was developed for BPA using Au-decorated magnetic reduced graphene oxide (Au/MrGO)-based recognition probe (RP) and DNA nanospheres (DNS)-based signal probe (SP) cooperative signal amplification. The DNS served as a signal molecule carrier and signal amplifier, while Au/MrGO acted as a signal amplifier and excellent medium for magnetic adsorption and separation. Moreover, utilizing the excellent magnetic properties of Au/MrGO eliminates the need for repetitive polishing and multi-step direct modification of the working electrode while ensuring that all detection processes take place in solution and that used Au/MrGO can be easily recycled. The proposed aptasensor exhibited not only good stability and selectivity, but also excellent sensitivity with a limit of detection (LOD) of 8.13 fg/mL (S/N = 3). The aptasensor's practicality was proven by spiking recovery tests on actual water samples and comparing the results with those detected by HPLC. The excellent sensitivity and selectivity make this aptasensor an alternative and promising avenue for rapid detection of BPA in environmental monitoring.

Robust PCA with Lw,∗ and L2,1 Norms: A Novel Method for Low-Quality Retinal Image Enhancement.

Nonmydriatic retinal fundus images often suffer from quality issues and artifacts due to ocular or systemic comorbidities, leading to potential inaccuracies in clinical diagnoses. In recent times, deep learning methods have been widely employed to improve retinal image quality. However, these methods often require large datasets and lack robustness in clinical settings. Conversely, the inherent stability and adaptability of traditional unsupervised learning methods, coupled with their reduced reliance on extensive data, render them more suitable for real-world clinical applications, particularly in the limited data context of high noise levels or a significant presence of artifacts. However, existing unsupervised learning methods encounter challenges such as sensitivity to noise and outliers, reliance on assumptions like cluster shapes, and difficulties with scalability and interpretability, particularly when utilized for retinal image enhancement. To tackle these challenges, we propose a novel robust PCA (RPCA) method with low-rank sparse decomposition that also integrates affine transformations τi, weighted nuclear norm, and the L2,1 norms, aiming to overcome existing method limitations and to achieve image quality improvement unseen by these methods. We employ the weighted nuclear norm (Lw,∗) to assign weights to singular values to each retinal images and utilize the L2,1 norm to eliminate correlated samples and outliers in the retinal images. Moreover, τi is employed to enhance retinal image alignment, making the new method more robust to variations, outliers, noise, and image blurring. The Alternating Direction Method of Multipliers (ADMM) method is used to optimally determine parameters, including τi, by solving an optimization problem. Each parameter is addressed separately, harnessing the benefits of ADMM. Our method introduces a novel parameter update approach and significantly improves retinal image quality, detecting cataracts, and diabetic retinopathy. Simulation results confirm our method's superiority over existing state-of-the-art methods across various datasets.

Quality Prediction Modeling for Industrial Processes Using Multiscale Attention-Based Convolutional Neural Network.

Soft sensors have been increasingly applied for quality prediction in complex industrial processes, which often have different scales of topology and highly coupled spatiotemporal features. However, the existing soft sensing models usually face difficulties in extracting the multiscale local spatiotemporal features in multicoupled complex process data and harnessing them to their full potential to improve the prediction performance. Therefore, a multiscale attention-based CNN (MSACNN) is proposed in this article to alleviate such problems. In MSACNN, convolutional kernels of different sizes are first designed in parallel in the convolutional layers, which can generate feature maps containing local spatiotemporal features at different scales. Meanwhile, a channel-wise attention mechanism is designed on the feature maps in parallel to get their attention weights, representing the significance of the local spatiotemporal feature at different scales. The superiority of the proposed MSACNN over the other state-of-the-art methods is validated through the performance evaluation in two real industrial processes.

Dapagliflozin ameliorates hepatic steatosis via suppressing LXRα-mediated synthesis of lipids and bile acids.

Nonalcoholic fatty liver disease (NAFLD) prevalence is rising globally with no pharmacotherapies approved. Hepatic steatosis is closely associated with progression and prognosis of NAFLD. Dapagliflozin, kind of sodium-glucose cotransporter 2 (SGLT2) inhibitor, was found to improve NAFLD in clinical trials, while the underlying mechanism remains poorly elucidated. Here, we reported that dapagliflozin effectively mitigated liver injury and relieved lipid metabolism disorders in vivo. Further investigation showed that dapagliflozin markedly suppressed Liver X Receptor α (LXRα)-mediated synthesis of de novo lipids and bile acids (BAs). In AML12 cells, our results proved dapagliflozin decreased lipid contents via inhibiting the expression of LXRα and downstream liposynthesis genes. Proteosome inhibitor MG132 eliminated the effect of dapagliflozin on LXRα-mediated signaling pathway, which suggested that dapagliflozin downregulated LXRα expression through increasing LXRα degradation. Knockdown of LXRα with siRNA abolished the reduction of lipogenesis from dapagliflozin treatment, indicating that LXRα might be the pivotal target for dapagliflozin to exhibit the aforementioned benefits. Furthermore, the data showed that dapagliflozin reversed gut dysbiosis induced by BAs disruption and altered gut microbiota profile to reduce intestinal lipids absorption. Together, our study deciphered a novel mechanism by which dapagliflozin relieved hepatic steatosis and highlighted the potential benefit of dapagliflozin in treating NAFLD.

Remote Manipulation of TRPV1 Signaling by Near-Infrared Light-Triggered Nitric Oxide Nanogenerators for Specific Cancer Therapy.

Specific activation of transient receptor potential vanilloid member 1 (TRPV1) channels provides a new avenue for cancer treatment by inducing excessive Ca2+ influx. However, controllable manipulation of TRPV1 signaling for clinical application has remained elusive due to the challenge in finding a mild and effective method of exerting external stimulus without adverse side effects in living systems. Herein, a TRPV1-targeting near-infrared (NIR) triggered nitric oxide (NO)-releasing nanoplatform (HCuS@PDA-TRPV1/BNN6) based on polydopamine (PDA) coated hollow copper sulfide nanoparticles (HCuS NPs) is developed for specific cancer therapy. Upon NIR irradiation, the NO donor BNN6 encapsulated in NIR-responsive nanovehicles can locally generate NO to activate TRPV1 channels and induce Ca2+ influx. This NIR controlled mode enables the nanoplatform to exert its therapeutic effects below the apoptotic threshold temperature (43°C), minimizing the photothermal damage to normal tissue. Integrating this special NO-mediated therapy with HCuS NPs mediated chemodynamic therapy, the designed nanoplatform exhibits a boosted anticancer activity with negligible systematic toxicity. Together, this study provides a promising strategy for site-specific cancer therapy by spatiotemporally controlled activation of surface ion channels, thus offering a solution to an unmet clinical need in cancer treatment.

Altered Functional Connectivity of Temporoparietal Lobe in Obstructive Sleep Apnea: A Resting-State fNIRS Study.

Obstructive Sleep Apnea (OSA), a sleep disorder with high prevalence, is normally accompanied by affective, autonomic, and cognitive abnormalities, and is deemed to be linked to functional brain alterations. To investigate alterations in brain functional connectivity properties in patients with OSA, a comparative analysis of global and local topological properties of brain networks was conducted between patients with OSA and healthy controls (HCs), utilizing functional near-infrared spectroscopy (fNIRS) imaging. A total of 148 patients with OSA and 150 healthy individuals were involved. Firstly, quantitative alterations in blood oxygen concentration, changes in functional connectivity, and variations in graph theory-based network topological characteristics were assessed. Then, with Mann-Whitney statistics, this study compared whether there are significant differences in the above characteristics between patients with OSA and HCs. Lastly, the study further examined the correlation between the altered characteristics and the apnea hypopnea index (AHI) using linear regression. Results revealed a higher mean and standard deviation of hemoglobin concentration in the superior temporal gyrus among patients with OSA compared to HCs. Resting-state functional connectivity (RSFC) exhibited a slight increase between the superior temporal gyrus and other specific areas in patients with OSA. Notably, neither patients with OSA nor HCs demonstrated significant small-world network properties. Patients with OSA displayed an elevated clustering coefficient (p < 0.05) and local efficiency (p < 0.05). Additionally, patients with OSA exhibited a tendency towards increased nodal betweenness centrality (p < 0.05) and degree centrality (p < 0.05) in the right supramarginal gyrus, as well as a trend towards higher betweenness centrality (p < 0.05) in the right precentral gyrus. The results of multiple linear regressions indicate that the influence of the AHI on RSFC between the right precentral gyrus and right superior temporal gyrus (p < 0.05), as well as between the right precentral gyrus and right supramarginal gyrus (p < 0.05), are statistically significant. These findings suggest that OSA may compromise functional brain connectivity and network topological properties in affected individuals, serving as a potential neurological mechanism underlying the observed abnormalities in brain function associated with OSA.

Alternating electric fields transform the intricate network of tumour vasculature into orderly parallel capillaries and enhance the anti-angiogenesis effect of bevacizumab.

The search for effective strategies to target tumour angiogenesis remains a critical goal of cancer research. We present a pioneering approach using alternating electric fields to inhibit tumour angiogenesis and enhance the therapeutic efficacy of bevacizumab. Chicken chorioallantoic membrane, cell viability and in vitro endothelial tube formation assays revealed that electric fields with a frequency of 1000 kHz and an electric intensity of 0.6 V/cm inhibited the growth of vascular endothelial cells and suppressed tumour-induced angiogenesis. In an animal U87MG glioma model, 1000 kHz electric fields inhibited tumour angiogenesis and suppressed tumour growth. As demonstrated by 3D vessel analysis, tumour vasculature in the control group was a stout, interwoven network. However, electric fields transformed it into slim, parallel capillaries that were strictly perpendicular to the electric field direction. This architectural transformation was accompanied by apoptosis of vascular endothelial cells and a notable reduction in tumour vessel number. Additionally, we found that the anti-angiogenesis and tumour-suppression effects of electric fields synergised with bevacizumab. The anti-angiogenic mechanisms of electric fields include disrupting spindle formation during endothelial cell division and downregulating environmental angiogenesis-related cytokines, such as interleukin-6, CXCL-1, 2, 3, 5 and 8, and matrix metalloproteinases. In summary, our findings demonstrate the potential of alternating electric fields (AEFs) as a therapeutic modality to impede angiogenesis and restrain cancer growth.

Causal Brain Network Predicts Surgical Outcomes in Patients With Drug-Resistant Epilepsy: A Retrospective Comparative Study.

Network neuroscience, especially causal brain network, has facilitated drug-resistant epilepsy (DRE) studies, while surgical success rate in patients with DRE is still limited, varying from 30%  âˆ¼  70 %. Predicting surgical outcomes can provide additional guidance to adjust treatment plans in time for poorly predicted curative effects. In this retrospective study, we aim to systematically explore biomarkers for surgical outcomes by causal brain network methods and multicenter datasets. Electrocorticogram (ECoG) recordings from 17 DRE patients with 58 seizures were included. Ictal ECoG within clinically annotated epileptogenic zone (EZ) and non-epileptogenic zone (NEZ) were separately computed using six different algorithms to construct causal brain networks. All the brain network results were divided into two groups, successful and failed surgeries. Statistical results based on the Mann-Whitney-U-test show that: causal connectivity of α -frequency band ( 8  âˆ¼  13 Hz) in EZ calculated by convergent cross mapping (CCM) gains the most significant differences between the surgical success and failure groups, with a P value of 7.85e-08 and Cohen's d effect size of 0.77. CCM-defined EZ brain network can also distinguish the successful and failed surgeries considering clinical covariates (clinical centers, DRE types) with [Formula: see text]. Based on the brain network features, machine learning models were developed to predict the surgical outcomes. Among them, the SVM classifier with Gaussian kernel function and Bayesian optimization demonstrates the highest average accuracy of 84.48% by 5-fold cross-validation, further indicating that the CCM-defined EZ brain network is a reliable biomarker for predicting DRE surgical outcomes.