Explainable spatio-temporal graph evolution learning with applications to dynamic brain network analysis during development.

Modeling dynamic interactions among network components is crucial to uncovering the evolution mechanisms of complex networks. Recently, spatio-temporal graph learning methods have achieved noteworthy results in characterizing the dynamic changes of inter-node relations (INRs). However, challenges remain: The spatial neighborhood of an INR is underexploited, and the spatio-temporal dependencies in INRs' dynamic changes are overlooked, ignoring the influence of historical states and local information. In addition, the model's explainability has been understudied. To address these issues, we propose an explainable spatio-temporal graph evolution learning (ESTGEL) model to model the dynamic evolution of INRs. Specifically, an edge attention module is proposed to utilize the spatial neighborhood of an INR at multi-level, i.e., a hierarchy of nested subgraphs derived from decomposing the initial node-relation graph. Subsequently, a dynamic relation learning module is proposed to capture the spatio-temporal dependencies of INRs. The INRs are then used as adjacent information to improve the node representation, resulting in comprehensive delineation of dynamic evolution of the network. Finally, the approach is validated with real data on brain development study. Experimental results on dynamic brain networks analysis reveal that brain functional networks transition from dispersed to more convergent and modular structures throughout development. Significant changes are observed in the dynamic functional connectivity (dFC) associated with functions including emotional control, decision-making, and language processing.

Highly Efficient Separation of Ethanol Amines and Cyanides via Ionic Magnetic Mesoporous Nanomaterials.

Simple and efficient sample pretreatment methods are important for analysis and detection of chemical warfare agents (CWAs) in environmental and biological samples. Despite many commercial materials or reagents that have been already applied in sample preparation, such as SPE columns, few materials with specificity have been utilized for purification or enrichment. In this study, ionic magnetic mesoporous nanomaterials such as poly(4-VB)@M-MSNs (magnetic mesoporous silicon nanoparticles modified by 4-vinyl benzene sulfonic acid) and Co2+@M-MSNs (magnetic mesoporous silicon nanoparticles modified by cobalt ions) with high absorptivity for ethanol amines (EAs, nitrogen mustard degradation products) and cyanide were successfully synthesized. The special nanomaterials were obtained by modification of magnetic mesoporous particles prepared based on co-precipitation using -SO3H and Co2+. The materials were fully characterized in terms of their composition and structure. The results indicated that poly(4-VB)@M-MSNs or Co2+@M-MSNs had an unambiguous core-shell structure with a BET of 341.7 m2·g-1 and a saturation magnetization intensity of 60.66 emu·g-1 which indicated the good thermal stability. Poly(4-VB)@M-MSNs showed selective adsorption for EAs while the Co2+@M-MSNs were for cyanide, respectively. The adsorption capacity quickly reached the adsorption equilibrium within the 90 s. The saturated adsorption amounts were MDEA = 35.83 mg·g-1, EDEA = 35.00 mg·g-1, TEA = 17.90 mg·g-1 and CN-= 31.48 mg·g-1, respectively. Meanwhile, the adsorption capacities could be maintained at 50-70% after three adsorption-desorption cycles. The adsorption isotherms were confirmed as the Langmuir equation and the Freundlich equation, respectively, and the adsorption mechanism was determined by DFT calculation. The adsorbents were applied for enrichment of targets in actual samples, which showed great potential for the verification of chemical weapons and the destruction of toxic chemicals.

Rapid detection of carbamate nerve agent analogues using dually functionalized gold nanoclusters.

Carbamate nerve agents (CMNAs) are a type of lethal cholinesterase inhibitor with one or more quaternary amine centres and aromatic rings. CMNAs have been recently added to the Annex on Chemicals of the Chemical Weapons Convention (CWC) and Schedules of Controlled Chemicals of China. In this study, a rapid, sensitive and selective method was developed for the fluorescence detection of ambenonium chloride (AC) through host-guest and electrostatic dual interactions between AC and cyclodextrin/11-mercaptoundecanoic acid (CD/MUA) dually functionalized gold nanoclusters (AuNCs). Through this method, AC was detected with a limit of detection of 10.0 ng/mL. Method evaluation showed high selectivity towards AC over other related compounds. The practical applicability was verified, as satisfactory recoveries were obtained for AC spiked in river water and urine, as well as Proficiency Test samples from Organisation for the Prohibition of Chemical Weapons (OPCW). In addition, a fluorescence sensing array comprising four AuNCs was designed to distinguish six carbamates and structurally similar compounds. This method provides a potential approach for the rapid, sensitive and selective recognition and detection of CMNAs.

A Hybrid Trust Model against Insider Packet Drop Attacks in Wireless Sensor Networks.

Quick and accurate detection of inside packet drop attackers is of critical importance to reduce the damage they can have on the network. Trust mechanisms have been widely used in wireless sensor networks for this purpose. However, existing trust models are not effective because they cannot distinguish between packet drops caused by an attack and those caused by normal network failure. We observe that insider packet drop attacks will cause more consecutive packet drops than a network abnormality. Therefore, we propose the use of consecutive packet drops to speed up the detection of inside packet drop attackers. In this article, we describe a new trust model based on consecutive drops and develop a hybrid trust mechanism to seamlessly integrate the new trust model with existing trust models. We perform extensive OPNET (Optimized Network Engineering Tool) simulations using a geographic greedy routing protocol to validate the effectiveness of our new model. The simulation results show that our hybrid trust model outperforms existing trust models for all types of inside packet drop attacks, not only in terms of detection speed and accuracy as it is designed for, but also in terms of other important network performance metrics, such as packet delivery rate, routing reliability, and energy efficiency.

Functional network estimation using multigraph learning with application to brain maturation study.

Although most dramatic structural changes occur in the perinatal period, a growing body of evidences demonstrates that adolescence and early adulthood are also important for substantial neurodevelopment. We were thus motivated to explore brain development during puberty by evaluating functional connectivity network (FCN) differences between childhood and young adulthood using multi-paradigm task-based functional magnetic resonance imaging (fMRI) measurements. Different from conventional multigraph based FCN construction methods where the graph network was built independently for each modality/paradigm, we proposed a multigraph learning model in this work. It promises a better fitting to FCN construction by jointly estimating brain network from multi-paradigm fMRI time series, which may share common graph structures. To investigate the hub regions of the brain, we further conducted graph Fourier transform (GFT) to divide the fMRI BOLD time series of a node within the brain network into a range of frequencies. Then we identified the hub regions characterizing brain maturity through eigen-analysis of the low frequency components, which were believed to represent the organized structures shared by a large population. The proposed method was evaluated using both synthetic and real data, which demonstrated its effectiveness in extracting informative brain connectivity patterns. We detected 14 hub regions from the child group and 12 hub regions from the young adult group. We show the significance of these findings with a discussion of their functions and activation patterns as a function of age. In summary, our proposed method can extract brain connectivity network more accurately by considering the latent common structures between different fMRI paradigms, which are significant for both understanding brain development and recognizing population groups of different ages.

Age-Aware Utility Maximization in Relay-Assisted Wireless Powered Communication Networks.

This article investigates a relay-assisted wireless powered communication network (WPCN), where the access point (AP) inspires the auxiliary nodes to participate together in charging the sensor, and then the sensor uses its harvested energy to send status update packets to the AP. An incentive mechanism is designed to overcome the selfishness of the auxiliary node. In order to further improve the system performance, we establish a Stackelberg game to model the efficient cooperation between the AP-sensor pair and auxiliary node. Specifically, we formulate two utility functions for the AP-sensor pair and the auxiliary node, and then formulate two maximization problems respectively. As the former problem is non-convex, we transform it into a convex problem by introducing an extra slack variable, and then by using the Lagrangian method, we obtain the optimal solution with closed-form expressions. Numerical experiments show that the larger the transmit power of the AP, the smaller the age of information (AoI) of the AP-sensor pair and the less the influence of the location of the auxiliary node on AoI. In addition, when the distance between the AP and the sensor node exceeds a certain threshold, employing the relay can achieve better AoI performance than non-relaying systems.

Clinical outcomes of revision with retrograde intermedullary nailing for failed plating of distal femoral fractures: a retrospective study.

PURPOSE: To assess the feasibility and effectiveness of retrograde intramedullary nail (RIN) revision surgeries for locking compression plate (LCP) failure in distal femoral fractures. METHODS: This retrospective study included 13 patients who suffered from metalwork failures after they initially underwent open reduction and LCP fixation. In patients who eventually underwent RIN revision from January 2014 to December 2016, range of motion (ROM) and Hospital for Special Surgery (HSS) scores obtained before surgery and at the final follow-up time were analysed. RESULTS: The average operative time was 155 minutes (range, 120-210 minutes), and the average blood loss volume was 650 ml (range, 200-1350 ml). There were two cases of complications (15.38%): one was calf muscle vein thrombosis, and the other was a superficial infection. No deep tissue infection or deep vein thrombosis was observed post-operatively. The average follow-up time was 16 months (range, 12-24 months). All fractures healed in a mean of 6.5 months (range, 4-12 months), and one patient underwent an additional bone graft surgery that did not involve a bone graft during the RIN revision operation (this eventually healed at 12 months post-operatively). The mean ROM before the operation was 86.92 ± 12.34°. At the final follow-up, the mean ROM was 112.69 ± 9.27°. There was a significant difference between pre-operative and post-operative ROM (P < 0.01). The mean HSS score improved significantly from 38.85 ± 9.62 points pre-operatively to 79.62 ± 5.42 points post-operatively. There was a significant difference between pre-operative and post-operative HSS scores (P < 0.01). CONCLUSIONS: RIN revision surgery achieved excellent clinical results in patients with LCP failure.

Spontaneously Regenerative Tough Hydrogels.

Sponges, Neofibularia nolitangere, can regenerate spontaneously after being broken down into small pieces, and the regenerated structure maintains the original appearance and function. Synthetic materials with such capabilities are highly desired but hardly achieved. Presented here is a sponge-inspired self-regenerative powder from a double-network (DN) tough hydrogel. Hydrogels are regenerated from their powder form, by addition of water, with preservation of the original appearance and mechanical properties. The powder-hydrogel-powder cycle can be repeated multiple times with little loss in mechanical properties, analogous to the regeneration of sponges. These DN hydrogels can be conveniently stored and easily shaped upon regeneration. This work may have implications in the development of regenerative materials for coatings and adhesives.

Global identification of peptidase specificity by multiplex substrate profiling.

We developed a simple and rapid multiplex substrate-profiling method to reveal the substrate specificity of any endo- or exopeptidase using liquid chromatography-tandem mass spectrometry sequencing. We generated a physicochemically diverse library of peptides by incorporating all combinations of neighbor and near-neighbor amino acid pairs into decapeptide sequences that are flanked by unique dipeptides at each terminus. Addition of a panel of evolutionarily diverse peptidases to a mixture of these tetradecapeptides generated information on prime and nonprime sites as well as on substrate specificity that matched or expanded upon known substrate motifs. This method biochemically confirmed the activity of the klassevirus 3C protein responsible for polypeptide processing and allowed granzyme B substrates to be ranked by enzymatic turnover efficiency using label-free quantitation of precursor-ion abundance. Additionally, the proteolytic secretions from schistosome parasitic flatworm larvae and a pancreatic cancer cell line were deconvoluted in a subtractive strategy using class-specific peptidase inhibitors.

The short- and long-term outcomes of laparoscopic versus open surgery for colorectal cancer: a meta-analysis.

PURPOSE: The aim of the study was to compare short- and long-term outcomes of laparoscopic surgery and conventional open surgery for colorectal cancer. METHODS: Published randomized controlled trial (RCT) reports of laparoscopic surgery and open surgery for colorectal cancer were searched, and short- and long-term factors were extracted to perform meta-analysis. RESULTS: A total of 15 RCT reports (6,557 colorectal cancer patients) were included in this study. Blood loss of laparoscopic surgery was less by 91.06 ml than open surgery (p = 0.044). Operation time was longer by 49.34 min (p = 0.000). The length of hospital stay was shorter by 2.64 days (p = 0.003). Incisional length was shorter by 9.23 cm (p = 0.000). Fluid intake was shorter by 0.70 day (p = 0.001). Bowel movement was earlier by 0.95 day (p = 0.000). Incidence of complications, blood transfusion, and 30 days death were significantly lower in laparoscopic surgery than in open surgery (p = 0.011, 0.000, 0.01). But there was no significant difference in lymph nodes (p = 0.535) and anastomotic leak (p = 0.924). There was also no significant difference in 3 and 5 years overall survival (p = 0.298, 0.966), disease-free survival (p = 0.487, 0.356), local recurrence (p = 0.270, 0.649), and no difference in 5 years distant recurrence (p = 0.838). CONCLUSIONS: Laparoscopic surgery is a mini-injured approach which can cure colorectal cancer safely and radically, and it is not different from conventional open surgery in long-term effectiveness, so laparoscopic surgery can be tried to widely use in colorectal cancer.

Integrated Brain Connectivity Analysis with fMRI, DTI, and sMRI Powered by Interpretable Graph Neural Networks.

Multimodal neuroimaging modeling has become a widely used approach but confronts considerable challenges due to heterogeneity, which encompasses variability in data types, scales, and formats across modalities. This variability necessitates the deployment of advanced computational methods to integrate and interpret these diverse datasets within a cohesive analytical framework. In our research, we amalgamate functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and structural MRI (sMRI) into a cohesive framework. This integration capitalizes on the unique strengths of each modality and their inherent interconnections, aiming for a comprehensive understanding of the brain's connectivity and anatomical characteristics. Utilizing the Glasser atlas for parcellation, we integrate imaging-derived features from various modalities-functional connectivity from fMRI, structural connectivity from DTI, and anatomical features from sMRI-within consistent regions. Our approach incorporates a masking strategy to differentially weight neural connections, thereby facilitating a holistic amalgamation of multimodal imaging data. This technique enhances interpretability at connectivity level, transcending traditional analyses centered on singular regional attributes. The model is applied to the Human Connectome Project's Development study to elucidate the associations between multimodal imaging and cognitive functions throughout youth. The analysis demonstrates improved predictive accuracy and uncovers crucial anatomical features and essential neural connections, deepening our understanding of brain structure and function. This study not only advances multi-modal neuroimaging analytics by offering a novel method for the integrated analysis of diverse imaging modalities but also improves the understanding of intricate relationship between the brain's structural and functional networks and cognitive development.

Exploring General Intelligence via Gated Graph Transformer in Functional Connectivity Studies.

Functional connectivity (FC) as derived from fMRI has emerged as a pivotal tool in elucidating the intricacies of various psychiatric disorders and delineating the neural pathways that underpin cognitive and behavioral dynamics inherent to the human brain. While Graph Neural Networks (GNNs) offer a structured approach to represent neuroimaging data, they are limited by their need for a predefined graph structure to depict associations between brain regions, a detail not solely provided by FCs. To bridge this gap, we introduce the Gated Graph Transformer (GGT) framework, designed to predict cognitive metrics based on FCs. Empirical validation on the Philadelphia Neurodevelopmental Cohort (PNC) underscores the superior predictive prowess of our model, further accentuating its potential in identifying pivotal neural connectivities that correlate with human cognitive processes.

Multiview hyperedge-aware hypergraph embedding learning for multisite, multiatlas fMRI based functional connectivity network analysis.

Recently, functional magnetic resonance imaging (fMRI) based functional connectivity network (FCN) analysis via graph convolutional networks (GCNs) has shown promise for automated diagnosis of brain diseases by regarding the FCNs as irregular graph-structured data. However, multiview information and site influences of the FCNs in a multisite, multiatlas fMRI scenario have been understudied. In this paper, we propose a Class-consistency and Site-independence Multiview Hyperedge-Aware HyperGraph Embedding Learning (CcSi-MHAHGEL) framework to integrate FCNs constructed on multiple brain atlases in a multisite fMRI study. Specifically, for each subject, we first model brain network as a hypergraph for every brain atlas to characterize high-order relations among multiple vertexes, and then introduce a multiview hyperedge-aware hypergraph convolutional network (HGCN) to extract a multiatlas-based FCN embedding where hyperedge weights are adaptively learned rather than employing the fixed weights precalculated in traditional HGCNs. In addition, we formulate two modules to jointly learn the multiatlas-based FCN embeddings by considering the between-subject associations across classes and sites, respectively, i.e., a class-consistency module to encourage both compactness within every class and separation between classes for promoting discrimination in the embedding space, and a site-independence module to minimize the site dependence of the embeddings for mitigating undesired site influences due to differences in scanning platforms and/or protocols at multiple sites. Finally, the multiatlas-based FCN embeddings are fed into a few fully connected layers followed by the soft-max classifier for diagnosis decision. Extensive experiments on the ABIDE demonstrate the effectiveness of our method for autism spectrum disorder (ASD) identification. Furthermore, our method is interpretable by revealing ASD-relevant brain regions that are biologically significant.

Magnetic mesoporous Fe3O4@nSiO2@mSiO2 nanoparticles for high-throughput mass spectrometry detection of hydrolyzed products of organophosphorus nerve agents.

Rapid and accurate detection of hydrolyzed products of organophosphorus nerve agents (OPNAs) is an important method to effectively confirm the use of these agents. OPNAs are rapidly hydrolyzed to the methyl phosphonates (MPs) in the environment, which can be used as environmental traceability marker for OPNAs. Herein, magnetic mesoporous materials combined with real-time in situ mass spectrometry (MS) were used to achieve high-throughput detection of MPs. Novel magnetic mesoporous nanoparticles Fe3O4@nSiO2@mSiO2 were synthesized via co-condensation of tetraethyl orthosilicate and cetyltrimethylammonium bromide (CTAB) on the surface of nonporous silica-coated Fe3O4 under alkaline conditions. CTAB templates were removed by the reflux of ethanol (0.0375 mM ammonium nitrate) to form mesoporous SiO2, which has a large specific surface area of 549 m2 g-1 and an excellent magnetization strength of 59.6 emu g-1. A quick, cost-effective, rugged, and safe magnetic preparation method, magnetic QuEChERS, was established with magnetic mesoporous nanoparticles (Fe3O4@nSiO2@mSiO2) as adsorption materials for direct analysis in real-time and tandem MS (DART-MS/MS) of MPs in environmental samples. The method exhibits good linearity (R2 > 0.992) in the range of 20.0-4.00 µg mL-1, the limits of detection were <5.00 ng mL-1, the limits of quantification were <20.0 ng mL-1, and the extraction recoveries were 70.2-98.1%, with relative standard deviations (RSDs) in the range of 1.97-10.6%. Additionally, using this method, analysis of 70 environmental samples could be completed within 20 min. Then, the M-QuEChERS-DART-MS/MS method was applied to the 52nd Organisation for the Prohibition of Chemical Weapons (OPCW) environmental spiked samples analysis, where the accuracy was 95.2-116%, and the RSD was 1.16-7.83%. The results demonstrated that Fe3O4@nSiO2@mSiO2 based on the QuEChERS method can quickly and efficiently remove the matrix of environmental samples and when coupled with the DART-MS/MS can achieve high-throughput determination of MPs in environmental samples.

A Demographic-Conditioned Variational Autoencoder for fMRI Distribution Sampling and Removal of Confounds.

Objective: fMRI and derived measures such as functional connectivity (FC) have been used to predict brain age, general fluid intelligence, psychiatric disease status, and preclinical neurodegenerative disease. However, it is not always clear that all demographic confounds, such as age, sex, and race, have been removed from fMRI data. Additionally, many fMRI datasets are restricted to authorized researchers, making dissemination of these valuable data sources challenging. Methods: We create a variational autoencoder (VAE)-based model, DemoVAE, to decorrelate fMRI features from demographics and generate high-quality synthetic fMRI data based on user-supplied demographics. We train and validate our model using two large, widely used datasets, the Philadelphia Neurodevelopmental Cohort (PNC) and Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP). Results: We find that DemoVAE recapitulates group differences in fMRI data while capturing the full breadth of individual variations. Significantly, we also find that most clinical and computerized battery fields that are correlated with fMRI data are not correlated with DemoVAE latents. An exception are several fields related to schizophrenia medication and symptom severity. Conclusion: Our model generates fMRI data that captures the full distribution of FC better than traditional VAE or GAN models. We also find that most prediction using fMRI data is dependent on correlation with, and prediction of, demographics. Significance: Our DemoVAE model allows for generation of high quality synthetic data conditioned on subject demographics as well as the removal of the confounding effects of demographics. We identify that FC-based prediction tasks are highly influenced by demographic confounds.

A Deep Dynamic Causal Learning Model to Study Changes in Dynamic Effective Connectivity during Brain Development.

OBJECTIVE: Brain dynamic effective connectivity (dEC), characterizes the information transmission patterns between brain regions that change over time, which provides insight into the biological mechanism underlying brain development. However, most existing methods predominantly capture fixed or temporally invariant EC, leaving dEC largely unexplored. METHODS: Herein we propose a deep dynamic causal learning model specifically designed to capture dEC. It includes a dynamic causal learner to detect time-varying causal relationships from spatio-temporal data, and a dynamic causal discriminator to validate these findings by comparing original and reconstructed data. RESULTS: Our model outperforms established baselines in the accuracy of identifying dynamic causalities when tested on the simulated data. When applied to the Philadelphia Neurodevelopmental Cohort, the model uncovers distinct patterns in dEC networks across different age groups. Specifically, the evolution process of brain dEC networks in young adults is more stable than in children, and significant differences in information transfer patterns exist between them. CONCLUSION: This study highlights the brain's developmental trajectory, where networks transition from undifferentiated to specialized structures with age, in accordance with the improvement of an individual's cognitive and information processing capability. SIGNIFICANCE: The proposed model consists of the identification and verification of dynamic causality, utilizing the spatio-temporal fusing information from fMRI. As a result, it can accurately detect dEC and characterize its evolution over age.

Interpretable Cognitive Ability Prediction: A Comprehensive Gated Graph Transformer Framework for Analyzing Functional Brain Networks.

Graph convolutional deep learning has emerged as a promising method to explore the functional organization of the human brain in neuroscience research. This paper presents a novel framework that utilizes the gated graph transformer (GGT) model to predict individuals' cognitive ability based on functional connectivity (FC) derived from fMRI. Our framework incorporates prior spatial knowledge and uses a random-walk diffusion strategy that captures the intricate structural and functional relationships between different brain regions. Specifically, our approach employs learnable structural and positional encodings (LSPE) in conjunction with a gating mechanism to efficiently disentangle the learning of positional encoding (PE) and graph embeddings. Additionally, we utilize the attention mechanism to derive multi-view node feature embeddings and dynamically distribute propagation weights between each node and its neighbors, which facilitates the identification of significant biomarkers from functional brain networks and thus enhances the interpretability of the findings. To evaluate our proposed model in cognitive ability prediction, we conduct experiments on two large-scale brain imaging datasets: the Philadelphia Neurodevelopmental Cohort (PNC) and the Human Connectome Project (HCP). The results show that our approach not only outperforms existing methods in prediction accuracy but also provides superior explainability, which can be used to identify important FCs underlying cognitive behaviors.

A Demographic-Conditioned Variational Autoencoder for fMRI Distribution Sampling and Removal of Confounds.

Objective: fMRI and derived measures such as functional connectivity (FC) have been used to predict brain age, general fluid intelligence, psychiatric disease status, and preclinical neurodegenerative disease. However, it is not always clear that all demographic confounds, such as age, sex, and race, have been removed from fMRI data. Additionally, many fMRI datasets are restricted to authorized researchers, making dissemination of these valuable data sources challenging. Methods: We create a variational autoencoder (VAE)-based model, DemoVAE, to decorrelate fMRI features from demographics and generate high-quality synthetic fMRI data based on user-supplied demographics. We train and validate our model using two large, widely used datasets, the Philadelphia Neurodevel-opmental Cohort (PNC) and Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP). Results: We find that DemoVAE recapitulates group differences in fMRI data while capturing the full breadth of individual variations. Significantly, we also find that most clinical and computerized battery fields that are correlated with fMRI data are not correlated with DemoVAE latents. An exception are several fields related to schizophrenia medication and symptom severity. Conclusion: Our model generates fMRI data that captures the full distribution of FC better than traditional VAE or GAN models. We also find that most prediction using fMRI data is dependent on correlation with, and prediction of, demographics. Significance: Our DemoVAE model allows for generation of high quality synthetic data conditioned on subject demographics as well as the removal of the confounding effects of demographics. We identify that FC-based prediction tasks are highly influenced by demographic confounds.

Preparation of ceftiofur-encapsulated hen-egg low-density lipoproteins and their antibacterial effects on intracellular Staphylococcus aureus.

Hen egg low-density lipoprotein (heLDL), as alternative of serum-derived LDL, was used as drug delivery system of ceftiofur (CEF). The CEF-loaded hen egg low-density lipoprotein (CEF-heLDL) with complete apolipoprotein structure and high drug loading rate was synthesized, possesses suitable particle size. CEF-heLDL undergoes cellular uptake and colocalizes with lysosomes in vitro. An intracellular infection model of the bovine endometrial epithelial cells and a coeliac-induced inflammation model of mice by Staphylococcus aureus (S. aureus) were established, and significantly lower intracellular S. aureus levels of CEF-heLDL group than CEF-free group (P < 0.001) was observed. The antibacterial efficacy was sustained for 24 h. Up to 400 mg/kg of CEF-heLDL, 20 times the clinical practice, were intraperitoneally administrated, and no significant toxicity signs on mice were observed. HeLDLs is an effective, safe, and cheap drug carrier, and could also be used for transmembrane delivering other antibiotics.

Multi-View Integrative Approach For Imputing Short-Chain Fatty Acids and Identifying Key factors predicting Blood SCFA.

Short-chain fatty acids (SCFAs) are the main metabolites produced by bacterial fermentation of dietary fiber within gastrointestinal tract. SCFAs produced by gut microbiotas (GMs) are absorbed by host, reach bloodstream, and are distributed to different organs, thus influencing host physiology. However, due to the limited budget or the poor sensitivity of instruments, most studies on GMs have incomplete blood SCFA data, limiting our understanding of the metabolic processes within the host. To address this gap, we developed an innovative multi-task multi-view integrative approach (M 2 AE, Multi-task Multi-View Attentive Encoders), to impute blood SCFA levels using gut metagenomic sequencing (MGS) data, while taking into account the intricate interplay among the gut microbiome, dietary features, and host characteristics, as well as the nuanced nature of SCFA dynamics within the body. Here, each view represents a distinct type of data input (i.e., gut microbiome compositions, dietary features, or host characteristics). Our method jointly explores both view-specific representations and cross-view correlations for effective predictions of SCFAs. We applied M 2 AE to two in-house datasets, which both include MGS and blood SCFAs profiles, host characteristics, and dietary features from 964 subjects and 171 subjects, respectively. Results from both of two datasets demonstrated that M 2 AE outperforms traditional regression-based and neural-network based approaches in imputing blood SCFAs. Furthermore, a series of gut bacterial species (e.g., Bacteroides thetaiotaomicron and Clostridium asparagiforme ), host characteristics (e.g., race, gender), as well as dietary features (e.g., intake of fruits, pickles) were shown to contribute greatly to imputation of blood SCFAs. These findings demonstrated that GMs, dietary features and host characteristics might contribute to the complex biological processes involved in blood SCFA productions. These might pave the way for a deeper and more nuanced comprehension of how these factors impact human health.