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Ontology can be used for the interpretation of natural language. To construct an anti-infective drug ontology, one needs to design and deploy a methodological step to carry out the entity discovery and linking. Medical synonym resources have been an important part of medical natural language processing (NLP). However, there are problems such as low precision and low recall rate. In this study, an NLP approach is adopted to generate candidate entities. Open ontology is analyzed to extract semantic relations. Six-word vector features and word-level features are selected to perform the entity linking. The extraction results of synonyms with a single feature and different combinations of features are studied. Experiments show that our selected features have achieved a precision rate of 86.77%, a recall rate of 89.03% and an F1 score of 87.89%. This paper finally presents the structure of the proposed ontology and its relevant statistical data.
Advances in biomedicine are largely fueled by exploring uncharted territories of human biology. Machine learning can both enable and accelerate discovery, but faces a fundamental hurdle when applied to unseen data with distributions that differ from previously observed ones -- a common dilemma in scientific inquiry. We have developed a new deep learning framework, called {\textit{Portal Learning}}, to explore dark chemical and biological space. Three key, novel components of our approach include: (i) end-to-end, step-wise transfer learning, in recognition of biology's sequence-structure-function paradigm, (ii) out-of-cluster meta-learning, and (iii) stress model selection. Portal Learning provides a practical solution to the out-of-distribution (OOD) problem in statistical machine learning. Here, we have implemented Portal Learning to predict chemical-protein interactions on a genome-wide scale. Systematic studies demonstrate that Portal Learning can effectively assign ligands to unexplored gene families (unknown functions), versus existing state-of-the-art methods, thereby allowing us to target previously "undruggable" proteins and design novel polypharmacological agents for disru
The spread of infectious disease is strongly influenced by social dynamics. In addition to infection risk, individuals vaccination decisions depend on prevailing social behavior: high infection levels and widespread vaccination can increase vaccine uptake, which in turn suppresses infection. This feedback can generate sustained oscillations in disease prevalence and vaccination behavior. Here, we study two such populations undergoing the same behavioral epidemiological limit cycle and introduce weak coupling between them through social influence. We show that coupling leads to synchronization of disease dynamics between the two groups. Moreover, we find that different payoff sensitivity may lead to synchronization or anti synchronization.
Infectious diseases continue to pose a serious threat to public health, underscoring the urgent need for effective computational approaches to screen novel anti-infective agents. Oligopeptides have emerged as promising candidates in antimicrobial research due to their structural simplicity, high bioavailability, and low susceptibility to resistance. Despite their potential, computational models specifically designed to predict associations between oligopeptides and infectious diseases remain scarce. This study introduces a prompt-guided graph-based contrastive learning framework (PGCLODA) to uncover potential associations. A tripartite graph is constructed with oligopeptides, microbes, and diseases as nodes, incorporating both structural and semantic information. To preserve critical regions during contrastive learning, a prompt-guided graph augmentation strategy is employed to generate meaningful paired views. A dual encoder architecture, integrating Graph Convolutional Network (GCN) and Transformer, is used to jointly capture local and global features. The fused embeddings are subsequently input into a multilayer perceptron (MLP) classifier for final prediction. Experimental resu
Chronic wound infections are sustained by dynamic 3D biofilm cycles involving maturation, dispersal, and recolonisation, yet existing in vitro models fail to reproduce these temporal and structural complexities. Here, we report a strategy that co-assembles a designed protease-inhibitory peptide amphiphile (PA-GF) with patient-derived wound fluid (WF) to reconstruct the complete biofilm life cycle in vitro. The PA-GF sequence incorporates an HWGF motif capable of binding and inhibiting matrix metalloproteinase-9 (MMP-9), thereby preserving the integrity of recolonised biofilms under proteolytic stress. Co-assembling with WF generated a living material that faithfully mimicked the biochemical and mechanical microenvironment of chronic wounds, supporting the formation of stable 3D biofilms capable of dispersal and recolonisation. Furthermore, we established a controllable polymicrobial infection model and validated its translational relevance through antibiotic susceptibility profiling and spatial microbiological analyses. Notably, the antibiotic response patterns of the PA/WF-derived biofilms closely mirrored those observed in a rat wound infection in vivo model. Collectively, our fi
Cytotoxic T lymphocytes eliminate infected or malignant cells, safeguarding surrounding tissues. Although experimental and systems-immunology studies have cataloged many molecular and cellular actors involved in an immune response, the design principles governing how the speed and magnitude of T-cell responses emerge from cellular decision-making remain elusive. Here, we recast the T-cell response as a feedback-controlled program, wherein the rates of activation, proliferation, differentiation and death are regulated through antigenic, pro- and anti-inflammatory cues. By exploring a broad class of feedback-controller designs as potential immune programs, we demonstrate how the speed and magnitude of T-cell responses emerge from optimizing signal-feedback to protect against diverse infection settings. We recover an inherent trade-off: infection clearance at the cost of immunopathology. We show how this trade-off is encoded into the logic of T-cell responses by hierarchical sensitivity to different immune signals. Notably, we find that designs that balance harm from acute infections and autoimmunity produce immune responses consistent with experimentally observed patterns of T-cell e
We investigate how homophily in adherence to anti-epidemic measures affects the final size of epidemics in social networks. Using a modified SIR model, we divide agents into two behavioral groups-compliant and non-compliant-and introduce transmission probabilities that depend asymmetrically on the behavior of both the infected and susceptible individuals. We simulate epidemic dynamics on two types of synthetic networks with tunable inter-group connection probability: stochastic block models (SBM) and networks with triadic closure (TC) that better capture local clustering. Our main result reveals a counterintuitive effect: under conditions where compliant infected agents significantly reduce transmission, increasing the separation between groups may lead to a higher fraction of infections in the compliant population. This paradoxical outcome emerges only in networks with clustering (TC), not in SBM, suggesting that local network structure plays a crucial role. These findings highlight that increasing group separation does not always confer protection, especially when behavioral traits amplify within-group transmission.
Chronic critical illness (CCI) is a disease state in which, following an initial insult, a patient neither recovers nor dies but instead remains in a state of critical illness. CCI is characterized by prolonged organ dysfunction, weight loss, and persistent increased vulnerability to infection. Recent data has shown that patients with CCI generally exhibit persistent immune dysfunction, characterized by prolonged elevation of specific pro-inflammatory cytokines. In this paper, we introduce a host response model that couples hematopoiesis dynamics with immune response to infection. Specifically, we incorporate the reactions between pro-inflammatory and anti-inflammatory signals with specific hematopoietic stem cell compartments with a reduced model of acute inflammation. We found that a maladaptive hematopoietic response to pathogenic insult is able to qualitatively reproduce similar behavior to that seen in CCI patients, namely the presence of a persistent, elevated level of pro-inflammatory cytokines. This suggests that maladaptive hematopoietic responses in vivo may play a role in the development of CCI.
Efficient sterilization of pathogens with cleaner methods is a critical concern for environmental disinfection and clinical anti-infective treatment. Plasma-activated water (PAW) is a promising alternative to chemical disinfectants and antibiotics for its strong sterilization ability and not inducing any acute toxicity, and only water and air are consumed during production. For more efficient water activation, plasma sources are commonly placed near or fully in contact with water as possible, but the risks of electrode corrosion and metal contamination of water threaten the safety and stability of PAW production. Herein, plasma-activated gas rich in high-valence NOx is generated by a hybrid plasma configuration and introduced into water for off-site PAW production. Plasma-generated O3 is found to dominate the gas-phase reactions for the formation of high-valence NOx. With the time-evolution of O3 concentration, gaseous NO3 radicals are produced behind N2O5 formation, but will be decomposed before N2O5 quenching. By decoupling the roles of gaseous NO3, N2O5, and O3 in the water activation, results show that short-lived aqueous species induced by gaseous NO3 radicals play the most cr
Immune events such as infection, vaccination, and a combination of the two result in distinct time-dependent antibody responses in affected individuals. These responses and event prevalences combine non-trivially to govern antibody levels sampled from a population. Time-dependence and disease prevalence pose considerable modeling challenges that need to be addressed to provide a rigorous mathematical underpinning of the underlying biology. We propose a time-inhomogeneous Markov chain model for event-to-event transitions coupled with a probabilistic framework for anti-body kinetics and demonstrate its use in a setting in which individuals can be infected or vaccinated but not both. We prove the equivalency of this approach to the framework developed in our previous work. Synthetic data are used to demonstrate the modeling process and conduct prevalence estimation via transition probability matrices. This approach is ideal to model sequences of infections and vaccinations, or personal trajectories in a population, making it an important first step towards a mathematical characterization of reinfection, vaccination boosting, and cross-events of infection after vaccination or vice vers
Deployment of anti-virus software is a common strategy for preventing and controlling the propagation of computer viruses and worms over a computer network. As the deployment of such programs is often limited due to monetary or operational costs, devising optimal strategies for their allocation and deployment can be of high value to the operation, performance, and resilience of the target networks. We study the effects of anti-virus deployment (i.e., "vaccination") strategies on the ability of a network to block the spread of a virus. Such ability is obtained when the network reaches "herd immunity", achieved when a large fraction of the network entities is immune to the infection, which provides protection even for entities which are not immune. We use a model that explicitly accounts for the inherent heterogeneity of network nodes activity and derive optimal strategies for anti-virus deployment. Numerical evaluations demonstrate that the system performance is very sensitive to the chosen strategy, and thus strategies which disregard the heterogeneous spread nature may perform significantly worse relatively to those derived in this work.
Fungal keratitis is a severe vision-threatening corneal infection with a prognosis influenced by fungal virulence and the host's immune defense mechanisms. The immune system, through its regulation of the inflammatory response, ensures cells and tissues can effectively activate defense mechanisms in response to infection and injury. However, there is still a lack of effective drugs that attenuate fungal virulence while relieving the inflammatory response caused by fungal keratitis. Therefore, finding effective treatments to solve these problems is particularly important. We synthesized ZIF-90 by water-based synthesis and characterized by SEM, XRD etc. In vitro experiments included CCK-8 and ELISA. These evaluations verified the disruptive effects of ZIF-90 on Aspergillus. fumigatus spore adhesion, morphology, cell membrane, and the effect of ZIF-90 on apoptosis. In addition, to investigate whether the metal-ligand zinc and the organic ligand imidazole act as essential factors in ZIF-90, we investigated the in vitro antimicrobial and anti-inflammatory effects of ZIF-8, ZIF-67, and MOF-74 (Zn) by MIC and ELISA experiments. ZIF-90 has therapeutic effects on fungal keratitis, which cou
Oncolytic virotherapy, utilizing genetically modified viruses to combat cancer and trigger anti-cancer immune responses, has garnered significant attention in recent years. In our previous work arXiv:2305.12386, we developed a stochastic agent-based model elucidating the spatial dynamics of infected and uninfected cells within solid tumours. Building upon this foundation, we present a novel stochastic agent-based model to describe the intricate interplay between the virus and the immune system; the agents' dynamics are coupled with a balance equation for the concentration of the chemoattractant that guides the movement of immune cells. We formally derive the continuum limit of the model and carry out a systematic quantitative comparison between this system of PDEs and the individual-based model in two spatial dimensions. Furthermore, we describe the traveling waves of the three populations, with the uninfected proliferative cells trying to escape from the infected cells while immune cells infiltrate the tumour. Simulations show a good agreement between agent-based approaches and numerical results for the continuum model. Some parameter ranges give rise to oscillations of cell numbe
Existing approaches defend against backdoor attacks in federated learning (FL) mainly through a) mitigating the impact of infected models, or b) excluding infected models. The former negatively impacts model accuracy, while the latter usually relies on globally clear boundaries between benign and infected model updates. However, model updates are easy to be mixed and scattered throughout in reality due to the diverse distributions of local data. This work focuses on excluding infected models in FL. Unlike previous perspectives from a global view, we propose Snowball, a novel anti-backdoor FL framework through bidirectional elections from an individual perspective inspired by one principle deduced by us and two principles in FL and deep learning. It is characterized by a) bottom-up election, where each candidate model update votes to several peer ones such that a few model updates are elected as selectees for aggregation; and b) top-down election, where selectees progressively enlarge themselves through picking up from the candidates. We compare Snowball with state-of-the-art defenses to backdoor attacks in FL on five real-world datasets, demonstrating its superior resistance to bac
Background: Fungal keratitis is a serious blinding eye disease. Traditional drugs used to treat fungal keratitis commonly have the disadvantages of low bioavailability, poor dispersion, and limited permeability. Purpose: To develop a new method for the treatment of fungal keratitis with improved bioavailability, dispersion, and permeability. Purpose: To develop a new method for the treatment of fungal keratitis with improved bioavailability, dispersion, and permeability. Methods: Zeolitic Imidazolate Framework-8 (ZIF-8) was formed by zinc ions and 2-methylimidazole linked by coordination bonds and characterized by Scanning electron microscopy (SEM), X-ray diffraction (XRD), and Zeta potential. The safety of ZIF-8 on HCECs and RAW 264.7 cells was detected by Cell Counting Kit-8 (CCK-8). The anti-inflammatory effects of ZIF-8 on RAW 246.7 cells were evaluated by Quantitative Real-Time PCR Experiments (qPCR) and Enzyme-linked immunosorbent assay (ELISA). Clinical score, Colony-Forming Units (CFU). In vivo, treatment with ZIF-8 reduced corneal fungal load and mitigated neutrophil infiltration in fungal keratitis, which effectively reduced the severity of keratitis in mice and alleviate
Treatment rate has always been one of the most important factors affecting the spread of infectious diseases. In this paper, we study a treatment function SIR model with treatment rate related to the maximum treatment capacity, whose infection rate is also saturated nonlinear. By calculating and analyzing based on planar dynamic system, the existence and stability of disease-free equilibrium point of the model are found. And it is also found that the situation is more complex for the endemic equilibrium point of the model. Under the conditions of meeting different parameters, the number of endemic equilibrium points may be zero, one or two, and the behavior of the endemic equilibrium point may be a saddle point, a stable or unstable anti-saddle point or center, or even a degenerate case.
Objectives. This review gathers information on the potential role of antihistamines as anti-infective agents and identifies gaps in research that have impaired its applicability in human health. Methods. The literature search encompassed MEDLINE, PubMed and Google Scholar from 1990 to 2022. Results. The literature search identified 12 antihistamines with activity against different pathogens. Eight molecules were second-generation antihistamines with intrinsically lower tendency to cross the blood brain barrier thereby with reduced side effects. Only five antihistamines had in vivo evaluations in rodents while one study utilized a wax moth model to determine astemizole anti-Cryptococcus sp. activity combined with fluconazole. In vitro studies showed that clemastine was active against Plasmodium, Leishmania, and Trypanosoma, while terfenadine suppressed Candida spp. and Staphylococcus aureus growth. In vitro assays found that SARS-coV-2 was inhibited by doxepin, azelastine, desloratadine, and clemastine. Different antihistamines inhibited Ebola virus (diphenhydramine, chlorcyclizine), Hepatitis C virus (chlorcyclizine), and Influenza virus (carbinoxamine, chlorpheniramine). Generally
Chronic infections of the human immunodeficiency virus (HIV) create a very complex co-evolutionary process, where the virus tries to escape the continuously adapting host immune system. Quantitative details of this process are largely unknown and could help in disease treatment and vaccine development. Here we study a longitudinal dataset of ten HIV-infected people, where both the B-cell receptors and the virus are deeply sequenced. We focus on simple measures of turnover, which quantify how much the composition of the viral strains and the immune repertoire change between time points. At the single-patient level, the viral-host turnover rates do not show any statistically significant correlation, however they correlate if the information is aggregated across patients. In particular, we identify an anti-correlation: large changes in the viral pool composition come with small changes in the B-cell receptor repertoire. This result seems to contradict the naive expectation that when the virus mutates quickly, the immune repertoire needs to change to keep up. However, we show that the observed anti-correlation naturally emerges and can be understood in terms of simple population-geneti
Bacteria can swim upstream due to hydrodynamic interactions with the fluid flow in a narrow tube, and pose a clinical threat of urinary tract infection to patients implanted with catheters. Coatings and structured surfaces have been proposed as a way to suppress bacterial contamination in catheters. However, there is no surface structuring or coating approach to date that thoroughly addresses the contamination problem. Here, based on the physical mechanism of upstream swimming, we propose a novel geometric design, optimized by an AI model predicting in-flow bacterial dynamics. The AI method, based on Fourier neural operator, offers significant speedups over traditional simulation methods. Using Escherichia coli, we demonstrate the anti-infection mechanism in quasi-2D micro-fluidic experiments and evaluate the effectiveness of the design in 3Dprinted prototype catheters under clinical flow rates. Our catheter design shows 1-2 orders of magnitude improved suppression of bacterial contamination at the upstream end of the catheter, potentially prolonging the in-dwelling time for catheter use and reducing the overall risk of catheter-associated urinary tract infections.
By integrating various simulation and experimental techniques, we discovered that antimicrobial peptides (AMPs) may achieve synergy at an optimal concentration and ratio, which can be caused by aggregation of the synergistic peptides. On multiple time and length scales, our studies obtain novel evidence of how peptide co-aggregation in solution can affect disruption of membranes by synergistic AMPs. Our findings provide crucial details about the complex molecular origins of AMP synergy, which will help guide the future development of synergistic AMPs as well as applications of anti-infective peptide cocktail therapies.