RÉSUMÉ
Antibiotic residues have been found in several aquatic ecosystems as a result of the widespread use of antibiotics in recent years, which poses a major risk to both human health and the environment. At present, photocatalytic degradation is the most effective and environmentally friendly method. Titanium silicon molecular sieve (TS-1) has been widely used as an industrial catalyst, but its photocatalytic application in wastewater treatment is limited due to its small pores and few active sites. In this paper, we report a method for preparing multistage porous TS-1 with a high specific surface area by alkali treatment. In the photocatalytic removal of CIP (ciprofloxacin) antibiotic wastewater experiments, the alkali-treated catalyst showed better performance in terms of interfacial charge transfer efficiency, which was 2.3 times higher than that of TS-1 synthesized by the conventional method, and it was found to maintain better catalytic performance in the actual water source. In addition, this research studied the effects of solution pH, contaminant concentration, and catalyst dosage on CIP degradation, while liquid chromatography-mass spectrometry (LC-MS) was used to identify intermediates in the degradation process and infer possible degradation pathways and the toxicity of CIP, and its degradation product was also analyzed using ECOSAR 2.2 software, and most of the intermediates were found to be nontoxic and nonharmful. Finally, a 3:5:1 artificial neural network model was established based on the experiments, and the relative importance of the influence of experimental conditions on the degradation rate was determined. The above results confirmed the feasibility and applicability of photocatalytic treatment of wastewater containing antibiotics using visible light excitation alkali post-treatment TS-1, which provided technical support and a theoretical basis for the photocatalytic treatment of wastewater containing antibiotics.
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Introduction: Gejie Zhilao Pill (GJZLP), a traditional Chinese medicine formula is known for its unique therapeutic effects in treating pulmonary tuberculosis. The aim of this study is to further investigate its underlying mechanisms by utilizing network pharmacology and molecular docking techniques. Methods: Using TCMSP database the components, potential targets of GJZLP were identified. Animal-derived components were supplemented through the TCMID and BATMAN-TCM databases. Tuberculosis-related targets were collected from the TTD, OMIM, and GeneCards databases. The intersection target was imported into the String database to build the PPI network. The Metascape platform was employed to carry out Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Heatmaps were generated through an online platform (https://www.bioinformatics.com.cn). Molecular docking was conducted between the core targets and core compounds to explore their binding strengths and patterns at the molecular level. Results: 61 active ingredients and 118 therapeutic targets were identified. Quercetin, Luteolin, epigallocatechin gallate, and beta-sitosterol showed relatively high degrees in the network. IL6, TNF, JUN, TP53, IL1B, STAT3, AKT1, RELA, IFNG, and MAPK3 are important core targets. GO and KEGG revealed that the effects of GJZLP on tuberculosis mainly involve reactions to bacterial molecules, lipopolysaccharides, and cytokine stimulation. Key signaling pathways include TNF, IL-17, Toll-like receptor and C-type lectin receptor signaling. Molecular docking analysis demonstrated a robust binding affinity between the core compounds and the core proteins. Stigmasterol exhibited the lowest binding energy with AKT1, indicating the most stable binding interaction. Discussion: This study has delved into the efficacious components and molecular mechanisms of GJZLP in treating tuberculosis, thereby highlighting its potential as a promising therapeutic candidate for the treatment of tuberculosis.
Sujet(s)
Médicaments issus de plantes chinoises , Simulation de docking moléculaire , Pharmacologie des réseaux , Médicaments issus de plantes chinoises/pharmacologie , Médicaments issus de plantes chinoises/composition chimique , Humains , Cartes d'interactions protéiques , Médecine traditionnelle chinoise , Antituberculeux/pharmacologie , Antituberculeux/usage thérapeutique , Antituberculeux/composition chimique , Mycobacterium tuberculosis/effets des médicaments et des substances chimiques , Tuberculose/traitement médicamenteux , Tuberculose/microbiologie , Transduction du signal/effets des médicaments et des substances chimiques , Animaux , Gene Ontology , Tuberculose pulmonaire/traitement médicamenteux , Tuberculose pulmonaire/microbiologieRÉSUMÉ
BACKGROUND: Iron deposition and ferroptosis are involved in ischemic stroke injury, but the choice of drugs for treatment is limited. PURPOSE: To investigate the potential neuroprotective effects of Rosmarinic acid (RosA) encapsulated within nanoliposomes (RosA-LIP) on ischemic stroke. METHODS: Wild-type (WT) and TfR1EC cKO (specific knockout of the TfR1 gene in BMECs) mice used to establish a dMCAO model, with simultaneous administration of RosA-LIP (20 mg/kg/d, i.p.) or RosA (20 mg/kg/d, i.p.). RESULTS: The successful synthesis of RosA-LIP resulted in enhanced stability and precise delivery in both the serum and brain. The administration of RosA-LIP effectively mitigated ischemia-induced behavioral abnormalities and pathological damage. RosA-LIP inhibited ferroptosis by ameliorating mitochondrial abnormalities, increasing GPX4 levels, and decreasing ACSL4/LPCAT3/Lox-dependent lipid peroxidation. RosA-LIP effectively improved bloodâbrain barrier (BBB) permeability, increased tight junctions (TJs) protein expression and reduced iron levels in ischemic tissue and brain microvascular endothelial cells (BMECs) by modulating FPN1 and TfR1 levels. Furthermore, RosA-LIP suppressed TfR1 to attenuate ACSL4/LPCAT3/Lox-mediated ferroptosis in TfR1EC cKO mice subjected to dMCAO. CONCLUSION: RosA-LIP effectively increased the brain level of RosA and protected against ferroptosis through the regulation of TfR1 in BMECs.
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Barrière hémato-encéphalique , Cinnamates , Depsides , Cellules endothéliales , Ferroptose , Liposomes , Récepteurs à la transferrine , , Animaux , Depsides/pharmacologie , Cinnamates/pharmacologie , Ferroptose/effets des médicaments et des substances chimiques , Récepteurs à la transferrine/métabolisme , Souris , Cellules endothéliales/effets des médicaments et des substances chimiques , Barrière hémato-encéphalique/effets des médicaments et des substances chimiques , Mâle , Souris knockout , Neuroprotecteurs/pharmacologie , Encéphale/effets des médicaments et des substances chimiques , Encéphale/métabolisme , Encéphalopathie ischémique/traitement médicamenteux , Modèles animaux de maladie humaine , Peroxydation lipidique/effets des médicaments et des substances chimiques , Souris de lignée C57BL , Accident vasculaire cérébral ischémique/traitement médicamenteuxRÉSUMÉ
The significance of iron in myocardial mitochondria function cannot be underestimated, because deviations in iron levels within cardiomyocytes may have profound detrimental effects on cardiac function. In this study, we investigated the effects of ferroportin 1 (FPN1) on cardiac iron levels and pathological alterations in mice subjected to chronic intermittent hypoxia (CIH). The cTNT-FPN1 plasmid was administered via tail vein injection to induce the mouse with FPN1 overexpression in the cardiomyocytes. CIH was established by exposing the mice to cycles of 21%-5% FiO2 for 3 min, 8 h per day. Subsequently, the introduction of hepcidin resulted in a reduction in FPN1 expression, and H9C2 cells were used to establish an IH model to further elucidate the role of FPN1. First, FPN1 overexpression ameliorated CIH-induced cardiac dysfunction, myocardial hypertrophy, mitochondrial damage and apoptosis. Second, FPN1 overexpression attenuated ROS levels during CIH. In addition, FPN1 overexpression mitigated CIH-induced cardiac iron accumulation. Moreover, the administration of hepcidin resulted in a reduction in FPN1 levels, further accelerating the CIH-induced levels of ROS, LIP and apoptosis in H9C2 cells. These findings indicate that the overexpression of FPN1 in cardiomyocytes inhibits CIH-induced cardiac iron accumulation, subsequently reducing ROS levels and mitigating mitochondrial damage. Conversely, the administration of hepcidin suppressed FPN1 expression and worsened cardiomyocyte iron toxicity injury.
Sujet(s)
Apoptose , Cardiomégalie , Transporteurs de cations , Hypoxie , Fer , Myocytes cardiaques , Espèces réactives de l'oxygène , Animaux , Myocytes cardiaques/métabolisme , Myocytes cardiaques/anatomopathologie , Cardiomégalie/métabolisme , Cardiomégalie/génétique , Cardiomégalie/anatomopathologie , Cardiomégalie/étiologie , Transporteurs de cations/métabolisme , Transporteurs de cations/génétique , Hypoxie/métabolisme , Hypoxie/complications , Souris , Espèces réactives de l'oxygène/métabolisme , Fer/métabolisme , Mâle , Hepcidines/métabolisme , Hepcidines/génétique , Lignée cellulaire , Souris de lignée C57BL , Modèles animaux de maladie humaine , RatsRÉSUMÉ
Bacillus spp. has been considered a promising source for identifying new antimicrobial substances, including anti-viral candidates. Here, we successfully isolated a number of bacteria strains from aged dry citrus peel (Chenpi). Of note, the culture supernatant of a new isolate named Bacillus subtilis LjM2 demonstrated strong inhibition of influenza A virus (IAV) infection in multiple experimental systems in vitro and in vivo. In addition, the anti-viral effect of LjM2 was attributed to its direct lysis of viral particles. Further analysis showed that a protease which we named CPAVM1 isolated from the culture supernatant of LjM2 was the key component responsible for its anti-viral function. Importantly, the therapeutic effect of CPAVM1 was still significant when applied 12 hours after IAV infection of experimental mice. Moreover, we found that the CPAVM1 protease cleaved multiple IAV proteins via targeting basic amino acid Arg or Lys. Furthermore, this study reveals the molecular structure and catalytic mechanism of CPAVM1 protease. During catalysis, Tyr75, Tyr77, and Tyr102 are important active sites. Therefore, the present work identified a special protease CPAVM1 secreted by a new strain of Bacillus subtilis LjM2 against influenza A virus infection via direct cleavage of critical viral proteins, thus facilitates future biotechnological applications of Bacillus subtilis LjM2 and the protease CPAVM1.
Sujet(s)
Antiviraux , Bacillus subtilis , Infections à Orthomyxoviridae , Animaux , Souris , Antiviraux/pharmacologie , Infections à Orthomyxoviridae/virologie , Virus de la grippe A/effets des médicaments et des substances chimiques , Virus de la grippe A/enzymologie , Peptide hydrolases/métabolisme , Chiens , Souris de lignée BALB C , Humains , Protéines virales/métabolisme , Protéines virales/génétique , Cellules rénales canines Madin-Darby , Femelle , Protéines bactériennes/métabolismeRÉSUMÉ
Evidence around the relationship between air pollution and the development of diabetes mellitus (DM) remains limited and inconsistent. To investigate the potential mediation effect of asprosin on the association between fine particulate matter (PM2.5), tropospheric ozone (O3) and blood glucose homeostasis. A case-control study was conducted on a total of 320 individuals aged over 60 years, including both diabetic and non-diabetic individuals, from six communities in Taiyuan, China, from July to September 2021. Generalized linear models (GLMs) suggested that short-term exposure to PM2.5 was associated with elevated fasting blood glucose (FBG), insulin resistance index (HOMA-IR), as well as reduced pancreatic ß-cell function index (HOMA-ß), and short-term exposure to O3 was associated with increased FBG and decreased HOMA-ß in the total population and elderly diabetic patients. Mediation analysis showed that asprosin played a mediating role in the relationship of PM2.5 and O3 with FBG, with mediating ratios of 10.2% and 18.4%, respectively. Our study provides emerging evidence supporting that asprosin mediates the short-term effects of exposure to PM2.5 and O3 on elevated FBG levels in an elderly population. Additionally, the elderly who are diabetic, over 70 years, and BMI over 24 kg/m2 are more vulnerable to air pollutants and need additional protection to reduce their exposure to air pollution.
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Polluants atmosphériques , Pollution de l'air , Diabète , Fibrilline-1 , Sujet âgé , Humains , Adulte d'âge moyen , Polluants atmosphériques/effets indésirables , Pollution de l'air/effets indésirables , Glycémie/métabolisme , Études cas-témoins , Chine/épidémiologie , Diabète/métabolisme , Exposition environnementale/analyse , Matière particulaire/analyse , Fibrilline-1/métabolisme , Adipokines/métabolismeRÉSUMÉ
The COVID pandemic fueled by emerging SARS-CoV-2 new variants of concern remains a major global health concern, and the constantly emerging mutations present challenges to current therapeutics. The spike glycoprotein is not only essential for the initial viral entry, but is also responsible for the transmission of SARS-CoV-2 components via syncytia formation. Spike-mediated cell-cell transmission is strongly resistant to extracellular therapeutic and convalescent antibodies via an unknown mechanism. Here, we describe the antibody-mediated spike activation and syncytia formation on cells displaying the viral spike. We found that soluble antibodies against receptor binding motif (RBM) are capable of inducing the proteolytic processing of spike at both the S1/S2 and S2' cleavage sites, hence triggering ACE2-independent cell-cell fusion. Mechanistically, antibody-induced cell-cell fusion requires the shedding of S1 and exposure of the fusion peptide at the cell surface. By inhibiting S1/S2 proteolysis, we demonstrated that cell-cell fusion mediated by spike can be re-sensitized towards antibody neutralization in vitro. Lastly, we showed that cytopathic effect mediated by authentic SARS-CoV-2 infection remain unaffected by the addition of extracellular neutralization antibodies. Hence, these results unveil a novel mode of antibody evasion and provide insights for antibody selection and drug design strategies targeting the SARS-CoV-2 infected cells.
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COVID-19 , SARS-CoV-2 , Humains , Anticorps , Membrane cellulaire , Glycoprotéine de spicule des coronavirus/génétiqueRÉSUMÉ
The innate immune responses, including inflammasome activation, are paramount for host defense against pathogen infection. In contrast to canonical and noncanonical inflammasome activation, in this study, heat-killed gram-negative bacteria (HK bacteria) were identified as single-step stimulators of the NLRP3 inflammasome in human monocytes, and they caused a moderate amount of IL-1ß to be released from cells. Time course experiments showed that this alternative inflammasome response was finished within a few hours. Further analysis showed that the intrinsically limited NLRP3 inflammasome activation response was due to the negative regulation of caspase-8 by the short isoform of cFLIP (cFLIPs), which was activated by NF-κB. In contrast, overexpressed cFLIPS, but not overexpressed cFLIPL, inhibited the activation of caspase-8 and the release of IL-1ß in response to HK bacteria infection in human monocytes. Furthermore, we demonstrated that TAK1 activity mediated the expression of cFLIPs and was upstream and essential for the caspase-8 cleavage induced by HK bacteria in human monocytes. The functional specificity of cFLIPs and TAK1 revealed unique responses of human monocytes to a noninvasive pathogen, providing novel insights into an alternative regulatory pathway of NLRP3 inflammasome activation.
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Inflammasomes , Monocytes , Humains , Inflammasomes/métabolisme , Protéine-3 de la famille des NLR contenant un domaine pyrine/métabolisme , Caspase 8/métabolisme , Immunité innée , Protéines régulatrices de l'apoptose/métabolisme , Interleukine-1 bêta/métabolismeRÉSUMÉ
This meta-analysis examined the post-operative wound effect of both obese and non-obese in total hip arthroplasty (THA) patients. To gather as complete an overview as possible, the researchers took advantage of 4 databases-PubMed, Embase, Cochrane Library and Web of Science-to conduct a critical assessment. Following the development of inclusion and exclusion criteria, the researchers evaluated the quality of each document. A total of 9 related trials were conducted to determine the 95% CI (CI) and OR using a fixed-effect model. The final meta-analyses were conducted with RevMan 5.3. Our findings indicate that there is no statistically significant benefit in terms of post-operative wound complications among obese and non-obese patients. Obese subjects had a significantly higher risk of injury than those without obesity (OR, 1.43; 95% CI, 1.04, 1.95, p = 0.03); obesity was also associated with a significantly higher risk of operative site infection than in non-obese subjects (OR, 1.96; 95% CI, 1.76, 2.18, p < 0.0001); and after surgery, there was also a significant increase in the risk of post-operative wound infections among obese subjects than in non-obese subjects (OR, 1.57; 95% CI, 1.34, 1.84, p < 0.0001). However, due to the small size of the cohort study in this meta-study, caution is required in the analysis. More randomized, controlled studies will be needed to validate these results.
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Arthroplastie prothétique de hanche , Plaie opératoire , Humains , Arthroplastie prothétique de hanche/effets indésirables , Arthroplastie prothétique de hanche/méthodes , Études de cohortes , Obésité/complications , Infection de plaie opératoire/étiologie , Plaie opératoire/étiologie , Complications postopératoires/étiologieRÉSUMÉ
Gram-positive bacterial infection causes high morbidity and mortality worldwide, while the underlying mechanism for host sensing bacterial components and initiating immune responses remains elusive. The NLRP3 inflammasome is a cytosolic multi-protein complex sensing a broad spectrum of endogenous danger signals and environmental irritants. In contrast to canonical NLRP3 inflammasome activation that needs both priming and activation signals, Lipopolysaccharide (LPS) from gram-negative bacteria activates the "one-step" NLRP3 inflammasome in human monocytes, which relies on the TLR4-TRIF-Caspase-8 signaling. Here, we show that in human monocytes, TLR2 agonists such as heat-killed gram-positive bacteria, peptidoglycan (PGN) or synthetic bacterial lipoprotein analog Pam3CysSerLys4 (Pam3CSK4) are able to induce the "one-step" NLRP3 inflammasome activation. Using genetic targeting and pharmacological inhibition approaches, it was found that TLR2 propagates signal through TRAF6, TAK1 and IKKß, ultimately activated NLRP3 independent of RelA. In addition, IKKß interacts with NLRP3 directly and affects NLRP3 inflammasome activation. These results reveal the signaling cascade downstream of TLR2 upon sensing gram-positive bacterial infection and activating the "one-step" NLRP3 inflammasome in human monocytes, which provides clue for controlling gram-positive bacterial infection-related inflammation.
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Inflammasomes , Monocytes , Humains , Inflammasomes/métabolisme , Monocytes/métabolisme , Protéine-3 de la famille des NLR contenant un domaine pyrine/métabolisme , Facteur-6 associé aux récepteurs de TNF/métabolisme , Récepteur de type Toll-2/métabolisme , I-kappa B Kinase/métabolisme , Protein-Serine-Threonine Kinases/métabolismeRÉSUMÉ
Abnormally expressed or malfunctioning proteins may affect or even damage cells, leading to the onset of diseases. Proteolysis targeting chimera (PROTAC) technology has been proven to be a fresh therapeutic strategy, superior to conventional small molecule inhibitors for the treatment of diseases caused by pathogenic proteins. Unlike conventional small molecule inhibitors that are occupancy-driven, PROTACs are heterobifunctional small molecules with catalytic properties. They combine with E3 ligases and target proteins to form a ternary complex, rendering the target protein ubiquitous and subsequently degraded by the proteasome. This paper focuses first on significant events in the development of PROTAC technology from 2001 to 2022, followed by a brief overview of various PROTACs categorized by target proteins. In addition, the applications of PROTACs in the treatment of diseases and fundamental biology are also under discussion.
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Or , Chimère ciblant la protéolyse , Protéolyse , Proteasome endopeptidase complex/métabolisme , Protéines/métabolisme , Ubiquitin-protein ligases/métabolisme , Atmosphère , TechnologieRÉSUMÉ
Aptasensors with high specificity have emerged as powerful tools for understanding various biological processes, thus providing tremendous opportunities for clinical diagnosis and prognosis. However, their applications in intracellular molecular imaging are largely impeded due to the low anti-interference capacity in biological environments and the moderate sensitivity to targets. Herein, a robust enzyme-free autocatalysis-driven feedback DNA circuit is devised for amplified aptasensing, for example, adenosine triphosphate (ATP) and thrombin, with a significantly improved sensitivity in living cells. This initiator-replicated hybridization chain reaction (ID-HCR) circuit was acquired by integrating the HCR circuit with the DNAzyme biocatalysis. Also, the autocatalysis-driven aptasensor consists of a recognition element and an amplification element. The recognition unit can specifically identify ATP or thrombin via a versatile conformational transformation, resulting in the exposure of the initiator to the autocatalysis-driven circuit. The ID-HCR element integrates the charming self-assembly characteristics of the HCR and the remarkable catalytic cleavage capacity of DNAzyme for realizing the continuously self-sustained regeneration or replication of trigger strands and for achieving an exponential signal gain. The autocatalysis-driven aptasensor has been validated for quantitative analysis of ATP and thrombin in vitro and for monitoring the corresponding aptamer substrates with various expressions in live cells. More importantly, the autocatalysis-driven aptasensor, as a versatile amplification strategy, holds enormous potential for analysis of other less abundant biomarkers by changing only the recognition element of the system.
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Adénosine triphosphate/analyse , Aptamères nucléotidiques/composition chimique , Techniques de biocapteur/méthodes , ADN catalytique/composition chimique , Thrombine/analyse , Adénosine triphosphate/composition chimique , Biocatalyse , Humains , Limite de détection , Cellules MCF-7 , Techniques d'amplification d'acides nucléiques , Thrombine/composition chimiqueRÉSUMÉ
Polynucleotide kinase (PNK) shows an in-depth correlationship with DNA repair and metabolism processes. The in situ visualization of intracellular PNK revealed an extremely biological significance in supplementing reliable and quantitative information on its spatiotemporal distribution in live cells. Herein, we developed a versatile cascaded DNA amplification circuit through the integration of catalytic DNA assembly and hybridization chain reaction circuits and realized the accurate evaluation of intracellular PNK activity via the Förster resonance energy transfer (FRET) principle. Initially, without PNK, trigger T was firmly caged in the PNK-recognizing hairpin HT, resulting in no disturbance of the concatenated circuit. However, with the introduction of PNK, the 5'-OH terminal of PNK-addressing HT was phosphorylated, then the phosphorylated HT could be subsequently digested by λ exonuclease (λ Exo) to produce trigger T of the cascaded DNA circuit. As a result, the integrated circuit was stimulated to produce an amplified FRET signal for quantitatively monitoring the activity of PNK. Due to the λ Exo-specific digestion of 5'-phosphate DNA and the high signal gain of the cascade circuit, our proposed strategy enables the sensitive analysis of PNK activity in vitro and in complex biological samples. Furthermore, our PNK-sensing platform was extensively explored in HeLa cells for realizing reliable intracellular PNK imaging and thus showed high potential in the future diagnosis and treatment of kinase-related diseases.
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Techniques de biocapteur , Polynucleotide 5'-hydroxyl-kinase , Bactériophage T4 , Transfert d'énergie par résonance de fluorescence , Cellules HeLa , Humains , Hybridation d'acides nucléiques , Polynucleotide 5'-hydroxyl-kinase/métabolismeRÉSUMÉ
Malaria is a life-threatening global epidemic disease and has caused more than 400,000 deaths in 2019. To control and prevent malaria, the development of a vaccine is a potential method. An effective malaria vaccine should either combine antigens from all stages of the malaria parasite's life cycle, or epitopes of multiple key antigens due to the complexity of the Plasmodium parasite. Malaria's random constructed antigen-1 (M.RCAg-1) is one of the recombinant vaccines, which was selected from a DNA library containing thousands of diverse multi-epitope chimeric antigen genes. Moreover, besides selecting an antigen, using an adjuvant is another important procedure for most vaccine development procedures. Freund's adjuvant is considered an effective vaccine adjuvant for malaria vaccine, but it cannot be used in clinical settings because of its serious side effects. Traditional adjuvants, such as alum adjuvant, are limited by their unsatisfactory immune effects in malaria vaccines, hence there is an urgent need to develop a novel, safe and efficient adjuvant. In recent years, Pickering emulsions have attracted increasing attention as novel adjuvant. In contrast to classical emulsions, Pickering emulsions are stabilized by solid particles instead of surfactant, having pliability and lateral mobility. In this study, we selected aluminum hydroxide gel (termed as "alum") as a stabilizer to prepare alum-stabilized Pickering emulsions (ALPE) as a malaria vaccine adjuvant. In addition, monophosphoryl lipid A (MPLA) as an immunostimulant was incorporated into the Pickering emulsion (ALMPE) to further enhance the immune response. In vitro tests showed that, compared with alum, ALPE and ALMPE showed higher antigen load rates and could be effectively endocytosed by J774a.1 cells. In vivo studies indicated that ALMPE could induce as high antibody titers as Freund's adjuvant. The biocompatibility study also proved ALMPE with excellent biocompatibility. These results suggest that ALMPE is a potential adjuvant for a malaria vaccine.
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In view of the demand of location awareness in a special complex environment, for an unmanned aerial vehicle (UAV) airborne multi base-station semi-passive positioning system, the hybrid positioning solutions and optimized site layout in the positioning system can effectively improve the positioning accuracy for a specific region. In this paper, the geometric dilution of precision (GDOP) formula of a time difference of arrival (TDOA) and angles of arrival (AOA) hybrid location algorithm is deduced. Mayfly optimization algorithm (MOA) which is a new swarm intelligence optimization algorithm is introduced, and a method to find the optimal station of the UAV airborne multiple base station's semi-passive positioning system using MOA is proposed. The simulation and analysis of the optimization of the different number of base stations, compared with other station layout methods, such as particle swarm optimization (PSO), genetic algorithm (GA), and artificial bee colony (ABC) algorithm. MOA is less likely to fall into local optimum, and the error of regional target positioning is reduced. By simulating the deployment of four base stations and five base stations in various situations, MOA can achieve a better deployment effect. The dynamic station configuration capability of the multi-station semi-passive positioning system has been improved with the UAV.
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Ephemeroptera , Algorithmes , Animaux , Simulation numériqueRÉSUMÉ
Catalytic DNA circuits represent a versatile toolbox for tracking intracellular biomarkers yet are constrained with low anti-interference capacity originating from their severe off-site activation. Herein, by introducing an unprecedented endogenous DNA repairing enzyme-powered pre-selection strategy, we develop a sequential and specific on-site activated catalytic DNA circuit for achieving the cancer cell-selective imaging of microRNA with high anti-interference capacity. Initially, the circuitry reactant is firmly caged by an elongated stabilizing duplex segment with a recognition/cleavage site of a cell-specific DNA repairing enzyme, which can prevent undesired signal leakage prior to its exposure to target cells. Then, the intrinsic DNA repairing enzyme of target cells can liberate the DNA probe for efficient intracellular microRNA imaging via the multiply guaranteed molecular recognition/activation procedures. This bioorthogonal regulated DNA circuit presents a modular and programmable amplification strategy for highly reliable assays of intracellular biomarkers, and provides a pivotal molecular toolbox for living systems.
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The accurate intracellular imaging of metal ions requires an exquisite site-specific activation of metal-ion sensors, for which the pervasive epigenetic regulation strategy can serve as an ideal alternative thanks to its orthogonal control feature and endogenous cell/tissue-specific expression pattern. Herein, a simple yet versatile demethylation strategy was proposed for on-site repairing-to-activating the metal-ion-targeting DNAzyme and for achieving the accurate site-specific imaging of metal ions in live cells. This endogenous epigenetic demethylation-regulating DNAzyme system was prepared by modifying the DNAzyme with an m6A methylation group that incapacitates the DNAzyme probe, thus eliminating possible off-site signal leakage, while the cell-specific demethylase-mediated removal of methylation modification could efficiently restore the initial catalytic DNAzyme for sensing metal ions, thus allowing a high-contrast bioimaging in live cells. This epigenetic repair-to-activate DNAzyme strategy may facilitate the robust visualization of disease-specific biomarkers for in-depth exploration of their biological functions.
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Acidithiobacillus spp. are the most active bacteria in bioleaching and bioremediation, because of their remarkable extreme environmental adaptabilities and unique metabolic characteristics. The researches on regulatory mechanisms of energy metabolism and stress resistance are critical for the understanding and application of Acidithiobacillus spp. However, the lack of an ideal reporter gene has become an obstacle for studying genes expression and regulatory mechanism in these chemoautotrophic bacteria. In this study, we reported the firefly luciferase as a reporter gene for Acidithiobacillus caldus (A. caldus) and created a firefly luciferase (Luc) reporter system. The Luc system was applied for the quantitative analysis of the transcription strength of the promoters of tetH gene and the feoA gene in A. caldus. Moreover, the regulating effect of ferric uptake regulator (Fur) on the feoP gene in A. caldus was determined using the Luc system. The Luc reporter system is not only used in the study of regulatory mechanism of A. caldus, but also applied in the researches of other Acidithiobacillus species. Therefore, this study provides a new useful tool for the studies on the molecular biological mechanism and synthetic biological modification of these chemoautotrophic bacteria, which would promote the industrial application of Acidithiobacillus spp.
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Acidithiobacillus , Luciférases des lucioles , Acidithiobacillus/génétique , Gènes rapporteurs , Luciférases des lucioles/génétique , Régions promotrices (génétique)RÉSUMÉ
DNA amplification is a useful technique for low-abundance biomarker detection and environmental monitoring because of its high signal-amplifying ability. However, intracellular application of DNA amplifiers remains challenging due to poor delivery efficiency and stability. Herein, we report an entropy-driven DNA amplifier-functionalized metal-organic framework (DNA amplifier-MOF) for the detection and imaging of multiple intracellular messenger RNAs (mRNAs). The DNA amplifier-MOF conjugate exhibits high cellular uptake, enhanced enzymatic stability, and good biocompatibility. Importantly, in the presence of phosphate ions, a surface-functionalized DNA amplifier can be released in cells with high efficiency, which facilitates the imaging of mRNA. This method is rapid and of high sensitivity/specificity, as validated in HepG2 and HL7702 cells for the imaging of TK1 and survivin mRNA, respectively. With further optimization, the strategy can become a powerful biotechnology tool for the detection of cancers at early stages and for elucidating biological processes.
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Techniques de biocapteur/méthodes , ADN/composition chimique , Réseaux organométalliques/composition chimique , ARN messager/génétique , HumainsRÉSUMÉ
To satisfy the service requirements of high accuracy and efficient life detection and location for search and rescue (SAR) missions after a disaster, we developed a passive positioning method to locate mobile phones by capturing the random access preamble, which can be applied to fourth-generation (4G) and even fifth-generation (5G) communication systems. We analyzed the characteristics of the random access procedure of a communication system and established a way to detect mobile phones by combining the time-difference-of-arrival (TDOA) estimation to determine the location. Then, we performed an experiment and a simulation of preamble sequence acquisition, and the results proved that the method is feasible and has high detection accuracy in high-noise conditions.