RESUMO
Epilepsy is a prevalent neurological disorder characterized by recurrent seizures. Validamycin A (VA) is an antibiotic fungicide that inhibits trehalase activity and is widely used for crop protection in agriculture. In this study, we identified a novel function of VA as a potential anti-seizure medication in a zebrafish epilepsy model. Electroencephalogram (EEG) analysis demonstrated that VA reduced pentylenetetrazol (PTZ)-induced seizures in the brains of larval and adult zebrafish. Moreover, VA reduced PTZ-induced irregular movement in a behavioral assessment of adult zebrafish. The developmental toxicity test showed no observable anatomical alteration when the zebrafish larvae were treated with VA up to 10 µM within the effective range. The median lethal dose of VA in adult zebrafish was > 14,000 mg/kg. These results imply that VA does not demonstrate observable toxicity in zebrafish at concentrations effective for generating anti-seizure activity in the EEG and alleviating abnormal behavior in the PTZ-induced epileptic model. Furthermore, the effectiveness of VA was comparable to that of valproic acid. These results indicate that VA may have a potentially safer anti-seizure profile than valproic acid, thus offering promising prospects for its application in agriculture and medicine.
Assuntos
Anticonvulsivantes , Modelos Animais de Doenças , Epilepsia , Pentilenotetrazol , Peixe-Zebra , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Pentilenotetrazol/efeitos adversos , Epilepsia/tratamento farmacológico , Epilepsia/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/induzido quimicamente , Eletroencefalografia , Ácido Valproico/farmacologia , Larva/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Inositol/análogos & derivadosRESUMO
This study addresses membrane biofouling in membrane bioreactors (MBRs) by exploring fungal-to-bacterial quorum quenching (QQ) strategies. While most research has been focused on bacterial-to-bacterial QQ tactics, this study identified fungal strain Vanrija sp. MS1, which is capable of degrading N-acyl-homoserine lactones (signaling molecules of Gram-negative bacteria). To determine the benefits of fungal over bacterial strains, after immobilization on fluidizing spherical beads in an MBR, MS1 significantly reduced the fouling rate by 1.8-fold compared to control MBR, decreased extracellular polymeric substance levels in the biofilm during MBR operation, and favorably changed microbial community and bacterial network, resulting in biofouling mitigation. It is noteworthy that, unlike Rhodococcus sp. BH4, MS1 enhanced QQ activity when switching from neutral to acidic conditions. These results suggest that MS1 has the potential for the effective treatment of acidic industrial wastewater sources such as semiconductor and secondary battery wastewater using MBRs.
Assuntos
Incrustação Biológica , Reatores Biológicos , Membranas Artificiais , Percepção de Quorum , Águas Residuárias , Purificação da Água , Incrustação Biológica/prevenção & controle , Reatores Biológicos/microbiologia , Águas Residuárias/química , Águas Residuárias/microbiologia , Purificação da Água/métodos , Biofilmes , Bactérias/metabolismoRESUMO
Prominent techniques such as real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and rapid kits are currently being explored to both enhance sensitivity and reduce assay time for diagnostic tests. Existing commercial molecular methods typically take several hours, while immunoassays can range from several hours to tens of minutes. Rapid diagnostics are crucial in Point-of-Care Testing (POCT). We propose an approach that integrates a time-series deep learning architecture and AI-based verification, for the enhanced result analysis of lateral flow assays. This approach is applicable to both infectious diseases and non-infectious biomarkers. In blind tests using clinical samples, our method achieved diagnostic times as short as 2 minutes, exceeding the accuracy of human analysis at 15 minutes. Furthermore, our technique significantly reduces assay time to just 1-2 minutes in the POCT setting. This advancement has the potential to greatly enhance POCT diagnostics, enabling both healthcare professionals and non-experts to make rapid, accurate decisions.
Assuntos
Doenças Transmissíveis , Aprendizado Profundo , Humanos , Testes de Diagnóstico Rápido , Testes Imediatos , Ensaio de Imunoadsorção Enzimática , Sensibilidade e Especificidade , Sistemas Automatizados de Assistência Junto ao LeitoRESUMO
Membrane bioreactors (MBRs) play a crucial role in wastewater treatment, but they face considerable challenges due to fouling. To tackle this issue, innovative strategies are needed. This study investigated the effectiveness of membrane reciprocation and quorum quenching (QQ) to control fouling in MBRs. The study compared MBRs using membrane reciprocation (30 rpm) and QQ (injecting media containing 100 or 200 mg/L BH4) with conventional MBRs employing different air-scouring intensities. The results demonstrated that combining membrane reciprocation (30 rpm) with QQ (200 mg/L BH4) significantly extended the service time of MBRs, making it approximately six times longer than conventional methods. Moreover, this approach reduced physically reversible resistance. The reduction in signal molecules related to biofouling due to QQ showcased its critical role in controlling biofouling, even under high shear caused by membrane reciprocation. However, the impact of QQ on microbial community structure appeared relatively insignificant when compared to factors such as operation time, aeration intensity, and membrane reciprocation. By combining membrane reciprocation and QQ, the study achieved a remarkable 81 % energy saving compared to extensive aeration (103 s-1 in velocity gradient), in addition to the extended service time. Importantly, this combined antifouling approach did not negatively affect microbial characteristics and wastewater treatment, emphasizing its effectiveness in MBRs. Overall, the findings of this study offer valuable insights for developing synergistic fouling control strategies in MBRs, significantly improving the energy efficiency of the wastewater treatment process.
Assuntos
Incrustação Biológica , Purificação da Água , Percepção de Quorum , Membranas Artificiais , Incrustação Biológica/prevenção & controle , Reatores Biológicos , Purificação da Água/métodosRESUMO
Quorum quenching (QQ) has effectively prevented biofouling in membrane bioreactors (MBRs) employing isolated QQ bacterial strains. However, the influence of QQ on the microbial population still needs to be fully understood. This research aims to analyze the microbial population in MBRs over an extended period (>250 days) under different conditions, such as varying aeration intensities and doses of QQ bacteria, QQ media, and types of feed. Results show that no significant changes occurred in the structure and diversity of the microbial community in the mixed liquor and biofilm due to QQ treatment. Canonical correspondence analysis did reveal that the microbial communities were strongly influenced by feed types and phases. The microbial community composition varied between bacterial habitats (i.e., mixed liquor and biofilm), showing the two dominant phyla Proteobacteria and Bacteroidota in the former and Proteobacteria and Chloroflexi in the latter. The co-occurrence network analysis indicated that the biofilm (with 163 edges) in the MBR fed with real wastewater exhibited a more intricate network than the biofilm (with 53 edges) in the MBR fed with synthetic wastewater. With QQ, the biofilm exhibited more positive edges than negative ones. The phylogenetic investigation of communities showed that QQ barely affects functional gene-related quorum sensing (e.g., bacterial chemotaxis, motility proteins, and secretion) in mixed liquor but in biofilms at relatively large QQ doses (> 75 mg/L BH4). This research sheds light on the bacterial QQ's role in reducing MBR biofouling and provides crucial insights into its underlying mechanisms.
Assuntos
Incrustação Biológica , Microbiota , Percepção de Quorum , Águas Residuárias , Filogenia , Reatores Biológicos/microbiologia , Incrustação Biológica/prevenção & controle , Bactérias , Proteobactérias , Membranas ArtificiaisRESUMO
Since many lateral flow assays (LFA) are tested daily, the improvement in accuracy can greatly impact individual patient care and public health. However, current self-testing for COVID-19 detection suffers from low accuracy, mainly due to the LFA sensitivity and reading ambiguities. Here, we present deep learning-assisted smartphone-based LFA (SMARTAI-LFA) diagnostics to provide accurate decisions with higher sensitivity. Combining clinical data learning and two-step algorithms enables a cradle-free on-site assay with higher accuracy than the untrained individuals and human experts via blind tests of clinical data (n = 1500). We acquired 98% accuracy across 135 smartphone application-based clinical tests with different users/smartphones. Furthermore, with more low-titer tests, we observed that the accuracy of SMARTAI-LFA was maintained at over 99% while there was a significant decrease in human accuracy, indicating the reliable performance of SMARTAI-LFA. We envision a smartphone-based SMARTAI-LFA that allows continuously enhanced performance by adding clinical tests and satisfies the new criterion for digitalized real-time diagnostics.
Assuntos
COVID-19 , Aprendizado Profundo , Humanos , Smartphone , Teste para COVID-19 , AlgoritmosRESUMO
Background: Pharmacological evaluation of antiepileptic drugs (AEDs) using mammalian animals takes long time and is expensive. The zebrafish is a species commonly used to study brain functions, neurological diseases, and drug toxicity, and attracts more attention as an alternative animal model to substitute or supplement mammalian animals in drug development. Electroencephalogram (EEG) is a key indicator for diagnosing brain diseases such as epilepsy, by directly measuring the brain activity. We propose a novel method for pharmacological evaluation of AEDs based on EEG from adult zebrafish, which allows researchers to select more clinically valuable drugs at the early stage of AED screening. Methods: To evaluate the efficacy of AEDs, zebrafish EEG signals were measured after administering six AEDs (valproate acid, gabapentin, ethosuximide, oxcarbazepine, tiagabine, and topiramate) at various doses to pentylenetetrazol (PTZ)-induced seizure models. The change in seizure activity was investigated according to doses. The antiepileptic effect was determined by observing a significant decrease in at least one out of three indicators of the number, total duration, and mean duration of ictal events. Results: Using EEG signals from adult zebrafish, antiepileptic effects were observed with all six AEDs. Among them, antiepileptic effects depending on dose were confirmed with valproate acid, gabapentin, ethosuximide, and tiagabine. Moreover, the 50% effective doses (ED50) of valproate acid and tiagabine were determined based on zebrafish EEG for the first time, indicating that the quantitative inter-species comparison of the AED efficacy is possible between zebrafish and mammals such as rodents. Significance: The results show that zebrafish can be used to effectively and quantitatively evaluate the efficacy of AEDs based on EEG, the same method to evaluate antiepileptic effects in mammals, suggesting that the proposed method can contribute in reducing the cost and duration of search for AEDs and thus accelerate the drug development cycles.
RESUMO
The effects of polystyrene microplastic (PS-MP) size on neurotoxicity remain to be evaluated at various microsizes, and the seizurogenic effects of PS-MPs are unknown. This study aimed to evaluate the swimming behavior of zebrafish larvae under light-dark transitions after exposure to four PS-MP sizes (i.e., 1, 6, 10, and 25 µm) at concentrations of 500, 5,000, and 50,000 particles/mL. Changes in electroencephalographic signals, seizure-related gene expression, and neurochemical concentrations were measured. Locomotor activity was inhibited only by 10-µm PS-MPs. According to electroencephalographic signals, the number and total duration of seizure-like events significantly increased by 10-µm PS-MPs, which was confirmed by the altered expression of seizure-related genes c-fos and pvalb5. Additionally, an increase in the levels of neurochemicals choline, betaine, dopamine, 3-methoxytyramine, and gamma-aminobutyric acid indicated that the observed hypoactivity and seizure-like behavior were associated with the dysregulation of the cholinergic, dopaminergic, and GABAergic systems. Overall, these findings demonstrate that exposure to PS-MPs can potentially cause seizurogenic effects in developing zebrafish embryos, and we highlight that PS-MPs 10 µm in size dominantly affect neurotoxicity.
Assuntos
Microplásticos , Poliestirenos , Animais , Microplásticos/toxicidade , Plásticos/toxicidade , Poliestirenos/metabolismo , Poliestirenos/toxicidade , Convulsões , Peixe-Zebra/metabolismoRESUMO
N-acylhomoserine lactone (AHL)-based bacterial communication through quorum sensing (QS) is one of the main causes of biofouling. Although quorum quenching (QQ) has proven to be an effective strategy against biofouling in membrane bioreactors (MBRs) for municipal wastewater treatment, its applicability for industrial wastewater treatment has rarely been studied. This is the first study to isolate QQ strains from the activated sludge used to treat industrial wastewater containing toxic tetramethylammonium hydroxide (TMAH) and 1-methyl-2-pyrrolidinone. The two QQ strains from genus Bacillus (SDC-U1 and SDC-A8) survived and effectively degraded QS signals in the presence of TMAH. They also showed resistance to toxic byproducts of TMAH degradation such as ammonium and formaldehyde. They effectively reduced the biofilm formation of Pseudomonas aeruginosa PAO1 and mixed community of activated sludge. The strains isolated in this study thus have the potential to be employed to reduce membrane biofouling in MBRs during the treatment of TMAH-containing wastewater.
Assuntos
Incrustação Biológica , Bactérias/metabolismo , Incrustação Biológica/prevenção & controle , Reatores Biológicos/microbiologia , Percepção de Quorum , Esgotos/microbiologia , Águas Residuárias/microbiologiaRESUMO
Bacterial quorum quenching (QQ) media with various structures (e.g., bead, cylinder, hollow cylinder, and sheet), which impart biofouling mitigation in membrane bioreactors (MBRs), have been reported. However, there has been a continuous demand for membranes with QQ capability. Thus, herein, we report a novel double-layered membrane comprising an outer layer containing a QQ bacterium (BH4 strain) on the polysulfone hollow fiber membrane. The double-layered composite membrane significantly inhibits biofilm formation (i.e., the biofilm density decreases by ~58%), biopolymer accumulation (e.g., polysaccharide), and signal molecule concentration (which decreases by ~38%) on the membrane surface. The transmembrane pressure buildup to 50 kPa of the BH4-embedded membrane (17.8 h ± 1.1) is delayed by more than thrice (p < 0.05) of the control with no BH4 in the membrane's outer layer (5.5 h ± 0.8). This finding provides new insight into fabricating antibiofouling membranes with a self-regulating property against biofilm growth.
RESUMO
Bacterial quorum quenching (QQ), whose mechanism involves the degradation of quorum-sensing signal molecules, is an effective strategy for controlling biofouling in membrane bioreactors (MBRs). However, MBRs operated at low temperatures, either due to cold climates or seasonal variations, exhibit severe deterioration in QQ efficiency. In this study, a modified culture method for Rhodococcus sp. BH4, a QQ bacterium, was developed to induce environmental adaptation in cold regions. BH4-L, which was prepared by the modified culture method, showed enhancement in QQ efficiency at low temperatures. The higher QQ efficiency obtained by employing BH4-L at 10 °C (compared with that obtained by employing BH4 at 10 °C) was attributed to the higher live/dead cell ratio in the BH4-L-entrapping beads. When BH4-L-entrapping beads were applied to lab-scale MBRs operated at low temperatures, membrane biofouling in MBRs at low temperatures was successfully mitigated because BH4-L could substantially reduce the concentration of signal molecules (N-acyl homoserine lactones) in the biocake. Employing BH4-L in QQ-MBRs could offer a novel solution to the problem of severe membrane biofouling in MBRs in cold regions.
Assuntos
Incrustação Biológica , Rhodococcus , Acil-Butirolactonas , Incrustação Biológica/prevenção & controle , Reatores Biológicos/microbiologia , Membranas Artificiais , Percepção de QuorumRESUMO
Photolytic quorum quenching by ultraviolet A (UVA) irradiation is an effective strategy for controlling membrane bioreactor (MBR) biofouling; however, its effects on MBR microbial communities and functional genes have not yet been explored. Here, we report on the effects of the UVA irradiation, which mitigates membrane biofouling, on the microbial community structures, alpha and beta diversities, and functional gene expressions in the MBR mixed liquor and biocake (membrane fouling layer) for the first time. The results show that the microbial communities become less diversified when alternating UVA is applied to the MBRs. The changes in the community structure are highly influenced by spatiotemporal factors, such as microbial habitats (mixed liquor and biocake) and reactor operation time, although UVA irradiation also has some impacts on the community. The relative abundance of the Sphingomonadaceae family, which can decompose the furan ring of autoinducer-2 (AI-2) signal molecules, becomes greater with continuous UVA irradiation. Xanthomonadaceae, which produces biofilm-degrading enzymes, is also more abundant with UVA photolysis than without it. Copies of monooxygenase and hydroxylase enzyme-related genes increase in the MBR with longer UVA exposures (i.e., continuous UVA). These enzymes seem to be inducible by UVA, enhancing the AI-2 inactivation. In conclusion, UVA irradiation alters the microbial community and the metabolism in the MBR, contributing to the membrane biofouling mitigation.
Assuntos
Incrustação Biológica , Microbiota , Reatores Biológicos , Expressão Gênica , Membranas Artificiais , Fotólise , Percepção de QuorumRESUMO
This paper proposes a novel online object-packing system which can measure the dimensions of every incoming object and calculate its desired position in a given container. Existing object-packing systems have the limitations of requiring the exact information of objects in advance or assuming them as boxes. Thus, this paper is mainly focused on the following two points: (1) Real-time calculation of the dimensions and orientation of an object; (2) Online optimization of the object's position in a container. The dimensions and orientation of the object are obtained using an RGB-D sensor when the object is picked by a manipulator and moved over a certain position. The optimal position of the object is calculated by recognizing the container's available space using another RGB-D sensor and minimizing the cost function that is formulated by the available space information and the optimization criteria inspired by the way people place things. The experimental results show that the proposed system successfully places the incoming various shaped objects in their proper positions.
RESUMO
Various quorum quenching (QQ) media have been developed to mitigate membrane biofouling in a membrane bioreactor (MBR). However, most are expensive, unstable and easily trapped in hollow fibre membranes. Here, a sol-gel method was used to develop a mesoporous silica medium entrapping a QQ bacterial strain (Rhodococcus sp. BH4). The new silica QQ medium was able to remove quorum sensing signalling molecules via both adsorption (owing to their mesoporous hydrophobic structure) and decomposition with an enzyme (lactonase), preventing MBR biofouling without affecting the water quality. It also demonstrated a relatively long life span due to its non-biodegradability and its relatively small particle size (<1.0 mm), which makes it less likely to clog in a hollow fibre membrane module.
Assuntos
Reatores Biológicos , Eliminação de Resíduos Líquidos , Incrustação Biológica , Membranas , Membranas Artificiais , Percepção de Quorum , Dióxido de Silício , Purificação da ÁguaRESUMO
The relationship between open innovation and company's competitive advantage, and organisational capabilities required remains to be explained. This study was conducted to answer the following questions. Does open innovation create organisation's competitive advantage? What types of capabilities are needed in the process of open innovation reaching competitive advantage, and what kind of relationship do they have? This study extends the scope of theoretical discussion about open innovation from the point of dynamic capability view. The results confirmed the statistical significance of the path linking open innovation to competitive advantage through product innovation. From the viewpoint of capabilities, transforming capability plays a role of significant prerequisite of sensing capability and seizing capability, having a direct or indirect significant effect on product innovation performance and competitive advantage sequentially. The results suggest that the linkages between the needed capabilities of organisation must be considered for performing open innovation to secure competitive advantage.
Assuntos
Competição Econômica , Inovação Organizacional , Indústrias/organização & administração , Modelos TeóricosRESUMO
Lab-scale membrane bioreactors (MBRs) were investigated at 12, 18, and 25 °C to identify the correlation between quorum sensing (QS) and biofouling at different temperatures. The lower the reactor temperature, the more severe the membrane biofouling measured in terms of the transmembrane pressure (TMP) during filtration. More extracellular polymeric substances (EPSs) that cause biofouling were produced at 18 °C than at 25 °C, particularly polysaccharides, closely associated with QS via the production of N-acyl homoserine lactone (AHL). However, at 12 °C, AHL production decreased, but the release of EPSs due to deflocculation increased the soluble EPS concentration. To confirm the temperature effect related to QS, bacteria producing AHL were isolated from MBR sludge and identified as Aeromonas sp., Leclercia sp., and Enterobacter sp. through a 16S rDNA sequencing analysis. Batch assays at 18 and 25 °C showed that there was a positive correlation between QS through AHL and biofilm formation in that temperature range.
Assuntos
Incrustação Biológica , Reatores Biológicos , Percepção de Quorum , 4-Butirolactona/análogos & derivados , 4-Butirolactona/metabolismo , Reatores Biológicos/microbiologia , Filtração , Esgotos/microbiologia , TemperaturaRESUMO
Efficient media designs for microbial quorum quenching (QQ) are essential to enable maximal biofouling control in membrane bioreactors (MBRs). Here we introduce a novel, double-layered, biocarrier design, which has QQ bacteria in the shell layer with biostimulating agents in the core, for effective membrane biofouling control. Confining the biostimulant within dense polymer materials permits its controlled release over an extended period. The provision of the biostimulant from the core to the outer shell, where the QQ bacteria are encapsulated, facilitates their prolonged survival and active life. The core-shell structured QQ bead with the stimulant inside, which inhibits biofilm formation, shows the best fouling mitigation in laboratory testing of MBRs, while enhancing signal molecule degradation and lowering exopolymer secretion. This new, layered QQ bead, which has dual functions of bioaugmentation and biostimulation, supports a highly efficient and sustainable anti-biofouling strategy.
Assuntos
Incrustação Biológica , Reatores Biológicos , Membranas , Membranas Artificiais , Percepção de QuorumRESUMO
In this study, the seasonality of the biofouling behavior of pilot-scale membrane bioreactors (MBRs) run in parallel with vacant sheets and quorum quenching (QQ) sheets using real municipal wastewater was investigated. QQ media delayed fouling, but low temperatures caused severe biofouling. The greater amount of extracellular polymeric substances (EPSs) produced in cold weather was responsible for the faster biofouling of a membrane, even with QQ media. There were significant negative relationships between EPS levels and water temperature. Cold weather was detrimental to the degradation of quorum sensing signal molecules by QQ sheets, whose activity was restored with a higher dose of QQ bacteria. The QQ bacteria in the sheets experienced a slight loss in activity during the early stage of the field test, but survived in the pilot-scale MBR fed with real wastewater. There were no significant discrepancies in treatment efficiency among conventional, vacant, and QQ MBRs.
Assuntos
Incrustação Biológica , Reatores Biológicos/microbiologia , Temperatura Baixa , Membranas Artificiais , Percepção de Quorum , Bactérias/metabolismo , Projetos Piloto , Águas Residuárias/microbiologiaRESUMO
Membrane biofouling, due to biofilm growth after planktonic bacteria attachment to a membrane, is a major bottleneck limiting the energy-efficient operation and maintenance of membrane bioreactors (MBRs). Microbial communications, known as quorum sensing (QS), are responsible for this biofouling behavior. Novel strategies for stopping this communication, known as quorum quenching (QQ), appear to be successful for biofouling control in MBRs used for wastewater treatment. This review describes recent information regarding the signal molecules and mechanisms responsible for QS behaviors, promising approaches for QQ (enzymatic, bacterial, fungal, photocatalytic, mimicking, and biostimulating methods), and efficient fabrication and use of QQ media for MBR applications. We discuss the opportunities and challenges of QQ techniques for their further improvement and practical use in MBRs.
Assuntos
Incrustação Biológica , Reatores Biológicos , Percepção de Quorum , Biofilmes , Reatores Biológicos/microbiologia , Águas Residuárias/microbiologiaRESUMO
Bacterial quorum quenching (QQ) by means of degrading signaling molecules has been applied to antibiofouling strategies in a membrane bioreactor (MBR) for wastewater treatment. However, the target signaling molecules have been limited to N-acyl homoserine lactones participating in intraspecies quorum sensing. Here, an approach to disrupting autoinducer-2 (AI-2) signaling molecules participating in interspecies quorum sensing was pursued as a next-generation antibiofouling strategy in an MBR for wastewater treatment. We isolated an indigenous QQ bacterium ( Acinetobacter sp. DKY-1) that can attenuate the expression of the quorum-sensing (QS) response through the inactivation of an autoinducer-2 signaling molecule, 4,5-dihydroxy-2,3-pentanedione (DPD), among four kinds of autoinducer-2 QS bacteria. DKY-1 released AI-2 QQ compounds, which were verified to be hydrophilic with a molecular weight of <400 Da. The addition of DKY-1 entrapping beads into an MBR significantly decreased DPD concentration and remarkably reduced membrane biofouling. This new approach, combining molecular biology with wastewater engineering, could enlarge the range of QQ-MBR for antibiofouling and energy savings in the field of wastewater treatment.