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The primer-guided entropy-driven high-throughput evolution of the DNA-based constitutional dynamic network, CDN, is introduced. The entropy gain associated with the process provides a catalytic principle for the amplified emergence of the CDN. The concept is applied to develop a programmable, spatially localized DNA circuit for effective in vitro and in vivo theranostic, gene-regulated treatment of cancer cells. The localized circuit consists of a DNA tetrahedron core modified at its corners with four tethers that include encoded base sequences exhibiting the capacity to emerge and assemble into a [2 × 2] CDN. Two of the tethers are caged by a pair of siRNA subunits, blocking the circuit into a mute, dynamically inactive configuration. In the presence of miRNA-21 as primer, the siRNA subunits are displaced, resulting in amplified release of the siRNAs silencing the HIF-1α mRNA and fast dynamic reconfiguration of the tethers into a CDN. The resulting CDN is, however, engineered to be dynamically reconfigured by miRNA-155 into an equilibrated mixture enriched with a DNAzyme component, catalyzing the cleavage of EGR-1 mRNA. The DNA tetrahedron nanostructure stimulates enhanced permeation into cancer cells. The miRNA-triggered entropy-driven reconfiguration of the spatially localized circuit leads to the programmable, cooperative bis-gene-silencing of HIF-1α and EGR-1 mRNAs, resulting in the effective and selective apoptosis of breast cancer cells and effective inhibition of tumors in tumor bearing mice.
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ADN , Entropía , Terapia Genética , MicroARNs , Humanos , Animales , MicroARNs/metabolismo , MicroARNs/genética , MicroARNs/química , ADN/química , Ratones , ARN Interferente Pequeño/química , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Línea Celular Tumoral , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , ADN Catalítico/química , ADN Catalítico/metabolismo , ADN Catalítico/genéticaRESUMEN
Self-assembled supramolecular DNA tetrahedra composed of programmed sequence-engineered complementary base-paired strands represent elusive nanostructures having key contributions to the development and diverse applications of DNA nanotechnology. By appropriate engineering of the strands, DNA tetrahedra of tuneable sizes and chemical functionalities were designed. Programmed functionalities for diverse applications were integrated into tetrahedra structures including sequence-specific recognition strands (aptamers), catalytic DNAzymes, nanoparticles, proteins, or fluorophore. The article presents a comprehensive review addressing methods to assemble and characterize the DNA tetrahedra nanostructures, and diverse applications of DNA tetrahedra framework are discussed. Topics being addressed include the application of structurally functionalized DNA tetrahedra nanostructure for the assembly of diverse optical or electrochemical sensing platforms and functionalized intracellular sensing and imaging modules. In addition, the triggered reconfiguration of DNA tetrahedra nanostructures and dynamic networks and circuits emulating biological transformations are introduced. Moreover, the functionalization of DNA tetrahedra frameworks with nanoparticles provides building units for the assembly of optical devices and for the programmed crystallization of nanoparticle superlattices. Finally, diverse applications of DNA tetrahedra in the field of nanomedicine are addressed. These include the DNA tetrahedra assisted permeation of nanocarriers into cells for imaging, controlled drug release, active chemodynamic/photodynamic treatment of target tissues, and regenerative medicine.
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BACKGROUND: The Atribacterota are widely distributed in the subsurface biosphere. Recently, the first Atribacterota isolate was described and the number of Atribacterota genome sequences retrieved from environmental samples has increased significantly; however, their diversity, physiology, ecology, and evolution remain poorly understood. RESULTS: We report the isolation of the second member of Atribacterota, Thermatribacter velox gen. nov., sp. nov., within a new family Thermatribacteraceae fam. nov., and the short-term laboratory cultivation of a member of the JS1 lineage, Phoenicimicrobium oleiphilum HX-OS.bin.34TS, both from a terrestrial oil reservoir. Physiological and metatranscriptomics analyses showed that Thermatribacter velox B11T and Phoenicimicrobium oleiphilum HX-OS.bin.34TS ferment sugars and n-alkanes, respectively, producing H2, CO2, and acetate as common products. Comparative genomics showed that all members of the Atribacterota lack a complete Wood-Ljungdahl Pathway (WLP), but that the Reductive Glycine Pathway (RGP) is widespread, indicating that the RGP, rather than WLP, is a central hub in Atribacterota metabolism. Ancestral character state reconstructions and phylogenetic analyses showed that key genes encoding the RGP (fdhA, fhs, folD, glyA, gcvT, gcvPAB, pdhD) and other central functions were gained independently in the two classes, Atribacteria (OP9) and Phoenicimicrobiia (JS1), after which they were inherited vertically; these genes included fumarate-adding enzymes (faeA; Phoenicimicrobiia only), the CODH/ACS complex (acsABCDE), and diverse hydrogenases (NiFe group 3b, 4b and FeFe group A3, C). Finally, we present genome-resolved community metabolic models showing the central roles of Atribacteria (OP9) and Phoenicimicrobiia (JS1) in acetate- and hydrocarbon-rich environments. CONCLUSION: Our findings expand the knowledge of the diversity, physiology, ecology, and evolution of the phylum Atribacterota. This study is a starting point for promoting more incisive studies of their syntrophic biology and may guide the rational design of strategies to cultivate them in the laboratory. Video Abstract.
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Carbono , Yacimiento de Petróleo y Gas , Filogenia , Carbono/metabolismo , Yacimiento de Petróleo y Gas/microbiología , ARN Ribosómico 16S/genética , Genoma Bacteriano , Alcanos/metabolismoRESUMEN
An aerobic, Gram-stain-negative, motile rod bacterium, designated as SYSU BS000021T, was isolated from a black soil sample in Harbin, Heilongjiang province, China. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the isolate belongs to the genus Methylobacterium, and showed the highest sequence similarity to Methylobacterium segetis KCTC 62267 T (98.51%) and Methylobacterium oxalidis DSM 24028 T (97.79%). Growth occurred at 20-37â (optimum, 28 °C), pH 6.0-8.0 (optimum, pH 7.0) and in the presence of 0% (w/v) NaCl. Polar lipids comprised of phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified aminolipid and one unidentified polar lipid. The major cellular fatty acids (> 5%) were C18:0 and C18:1 ω7c and/or C18:1 ω6c. The predominant respiratory quinone was Q-10. The genomic G + C content was 68.36% based on the whole genome analysis. The average nucleotide identity (≤ 83.5%) and digital DNA-DNA hybridization (≤ 27.3%) values between strain SYSU BS000021T and other members of the genus Methylobacterium were all lower than the threshold values recommended for distinguishing novel prokaryotic species. Based on the results of phenotypic, chemotaxonomic and phylogenetic analyses, strain SYSU BS000021T represents a novel species of the genus Methylobacterium, for which the name Methylobacterium nigriterrae sp. nov. is proposed. The type strain of the proposed novel species is SYSU BS000021T (= GDMCC 1.3814 T = KCTC 8051 T).
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Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano , Ácidos Grasos , Methylobacterium , Filogenia , ARN Ribosómico 16S , Microbiología del Suelo , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , Ácidos Grasos/análisis , Ácidos Grasos/química , Methylobacterium/genética , Methylobacterium/clasificación , Methylobacterium/aislamiento & purificación , China , Hibridación de Ácido Nucleico , Análisis de Secuencia de ADN , Fosfolípidos/análisisRESUMEN
OBJECTIVE: The family Paenibacillaceae is linked to the order Caryophanales. Paenibacillaceae members residing in compost or soil play crucial roles in nutrient recycling and breaking down complex organic materials. However, our understanding of Paenibacillaceae remains limited. METHODS: Strain SYSU GA230002T was conclusively identified using a polyphasic taxonomic approach frequently utilized in bacterial systematics. Standard microbiological techniques were employed to characterize the morphology and biochemistry of strain SYSU GA230002T. RESULTS: An anaerobic and gram--negative bacterium, designated SYSU GA230002T, was isolated from geothermally heated soil of Tengchong, Yunnan Province, south-west China. Phylogenetic analyses based on 16S rRNA gene sequences and genomes showed that strain SYSU GA230002T belongs to the family Paenibacillaceae. 16S rRNA gene sequence similarity (<94.0 %), ANI (<71.95 %) and AAI values (<58.67 %) between strain SYSU GA230002T with other members of the family were lower than the threshold values recommended for distinguishing novel species. Growth was observed at 30-45 °C (optimum, 37 °C), pH 7.0-8.0 (optimum, pH 7.5) and in 0-3.0 % (w/v) NaCl concentrations (optimum, 0 %). The major fatty acids detected were anteiso-C15:0, iso-C16:0 and iso-C17:0. The polar lipids included diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, one unidentified phospholipid, one unidentified aminolipid and two unidentified glycolipids. The respiratory quinone was MK-7. The DNA G + C content of strain SYSU GA230002T was 49.87 %. CONCLUSION: Based on the results of morphological, physiological properties, and chemotaxonomic characteristics, this strain is proposed to represent a new species of a new genus Ferviditalea candida gen. nov., sp. nov. The type strain of the type species is SYSU GA230002T (=KCTC 25726T = GDMCC 1.4160T).
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Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano , Ácidos Grasos , Fosfolípidos , Filogenia , ARN Ribosómico 16S , Microbiología del Suelo , ARN Ribosómico 16S/genética , Ácidos Grasos/análisis , Ácidos Grasos/química , China , ADN Bacteriano/genética , Fosfolípidos/análisis , Análisis de Secuencia de ADNRESUMEN
Early diagnosis of drug-induced kidney injury (DIKI) is essential for clinical treatment and intervention. However, developing a reliable method to trace kidney injury origins through retrospective studies remains a challenge. In this study, we designed ordered fried-bun-shaped Au nanocone arrays (FBS NCAs) to create microarray chips as a surface-enhanced Raman scattering (SERS) analysis platform. Subsequently, the principal component analysis (PCA)-two-layer nearest neighbor (TLNN) model was constructed to identify and analyze the SERS spectra of exosomes from renal injury induced by cisplatin and gentamycin. The established PCA-TLNN model successfully differentiated the SERS spectra of exosomes from renal injury at different stages and causes, capturing the most significant spectral features for distinguishing these variations. For the SERS spectra of exosomes from renal injury at different induction times, the accuracy of PCA-TLNN reached 97.8% (cisplatin) and 93.3% (gentamicin). For the SERS spectra of exosomes from renal injury caused by different agents, the accuracy of PCA-TLNN reached 100% (7 days) and 96.7% (14 days). This study demonstrates that the combination of label-free exosome SERS and machine learning could serve as an innovative strategy for medical diagnosis and therapeutic intervention.
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Cisplatino , Oro , Aprendizaje Automático , Análisis de Componente Principal , Espectrometría Raman , Espectrometría Raman/métodos , Animales , Oro/química , Exosomas/química , Gentamicinas/análisis , Nanopartículas del Metal/químicaRESUMEN
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease globally. Currently, there are no effective drugs for the treatment of DN. Although several studies have reported the therapeutic potential of mesenchymal stem cells, the underlying mechanisms remain largely unknown. Here, we report that both human umbilical cord MSCs (UC-MSCs) and UC-MSC-derived exosomes (UC-MSC-exo) attenuate kidney damage, and inhibit epithelial-mesenchymal transition (EMT) and renal fibrosis in streptozotocin-induced DN rats. Strikingly, the Hedgehog receptor, smoothened (SMO), was significantly upregulated in the kidney tissues of DN patients and rats, and positively correlated with EMT and renal fibrosis. UC-MSC and UC-MSC-exo treatment resulted in decrease of SMO expression. In vitro co-culture experiments revealed that UC-MSC-exo reduced EMT of tubular epithelial cells through inhibiting Hedgehog/SMO pathway. Collectively, UC-MSCs inhibit EMT and renal fibrosis by delivering exosomes and targeting Hedgehog/SMO signaling, suggesting that UC-MSCs and their exosomes are novel anti-fibrotic therapeutics for treating DN.
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Diabetes Mellitus , Nefropatías Diabéticas , Exosomas , Células Madre Mesenquimatosas , Humanos , Ratas , Animales , Nefropatías Diabéticas/metabolismo , Exosomas/metabolismo , Receptor Smoothened , Proteínas Hedgehog/metabolismo , Fibrosis , Células Madre Mesenquimatosas/metabolismo , Cordón Umbilical/metabolismo , Diabetes Mellitus/metabolismoRESUMEN
Two-dimensional material-supported single metal atom catalysts have been extensively studied and proved effective in electrocatalytic reactions in recent years. In this work, we systematically investigate the OER catalytic properties of single metal atoms supported by the NiN2 monolayer. Several typical transition metals with high single atom catalytic activity, such as Fe, Co, Ru, Rh, Pd, Ir, and Pt, were selected as catalytic active sites. The energy calculations show that transition metal atoms (Fe, Co, Ru, Rh, Pd, Ir, and Pt) are easily embedded in the NiN2 monolayer with Ni vacancies due to the negative binding energy. The calculated OER overpotentials of Fe, Co, Ru, Rh, Pd, Ir and Pt embedded NiN2 monolayers are 0.92 V, 0.47 V, 1.13 V, 0.66 V, 1.25 V, 0.28 V, and 0.94 V, respectively. Compared to the 0.57 V OER overpotential of typical OER noble metal catalysts IrO2, Co@NiN2 and Ir@NiN2 exhibit high OER catalytic activity due to lower overpotential, especially for Ir@NiN2. The high catalytic activity of the Ir embedded NiN2 monolayer can be explained well by the d-band center model. It is found that the adsorption strength of the embedded TM atoms with intermediates follows a linear relationship with their d-band centers. Besides, the overpotential of the Ir embedded NiN2 monolayer can be further reduced to 0.24 V under -2% biaxial strain. Such findings are expected to be employed in more two-dimensional material-supported single metal atom catalyzed reactions.
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The photochemical deprotection of structurally engineered o-nitrobenzylphosphate-caged hairpin nucleic acids is introduced as a versatile method to evolve constitutional dynamic networks, CDNs. The photogenerated CDNs, in the presence of fuel strands, interact with auxiliary CDNs, resulting in their dynamically equilibrated reconfiguration. By modification of the constituents associated with the auxiliary CDNs with glucose oxidase (GOx)/horseradish peroxidase (HRP) or the lactate dehydrogenase (LDH)/nicotinamide adenine dinucleotide (NAD+) cofactor, the photogenerated CDN drives the orthogonal operation upregulated/downregulated operation of the GOx/HRP and LDH/NAD+ biocatalytic cascade in the conjugate mixture of auxiliary CDNs. Also, the photogenerated CDN was applied to control the reconfiguration of coupled CDNs, leading to upregulated/downregulated formation of the antithrombin aptamer units, resulting in the dictated inhibition of thrombin activity (fibrinogen coagulation). Moreover, a reaction module consisting of GOx/HRP-modified o-nitrobenzyl phosphate-caged DNA hairpins, photoresponsive caged auxiliary duplexes, and nickase leads upon irradiation to the emergence of a transient, dissipative CDN activating in the presence of two alternate auxiliary triggers, achieving transient operation of up- and downregulated GOx/HRP biocatalytic cascades.
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ADN Catalítico , ADN Catalítico/metabolismo , NAD , ADN/genética , Biocatálisis , OligonucleótidosRESUMEN
Abdominal Aortic Aneurysm (AAA) is a life-threatening vascular disease characterized by the weakening and ballooning of the abdominal aorta, which has no effective therapeutic approaches due to unclear molecular mechanisms. Using single-cell RNA sequencing, we analyzed the molecular profile of individual cells within control and AAA abdominal aortas. We found cellular heterogeneity, with increased plasmacytoid dendritic cells and reduced endothelial cells and vascular smooth muscle cells (VSMCs) in AAA. Up-regulated genes in AAA were associated with muscle tissue development and apoptosis. Genes controlling VSMCs aberrant switch from contractile to synthetic phenotype were significantly enriched in AAA. Additionally, VSMCs in AAA exhibited cell senescence and impaired oxidative phosphorylation. Similar observations were made in a mouse model of AAA induced by Angiotensin II, further affirming the relevance of our findings to human AAA. The concurrence of gene expression changes between human and mouse highlighted the impairment of oxidative phosphorylation as a potential target for intervention. Nicotinamide phosphoribosyltransferase (NAMPT, also named VISFATIN) signaling emerged as a signature event in AAA. NAMPT was significantly downregulated in AAA. NAMPT-extracellular vesicles (EVs) derived from mesenchymal stem cells restored NAMPT levels, and offered protection against AAA. Furthermore, NAMPT-EVs not only repressed injuries, such as cell senescence and DNA damage, but also rescued impairments of oxidative phosphorylation in both mouse and human AAA models, suggesting NAMPT supplementation as a potential therapeutic approach for AAA treatment. These findings shed light on the cellular heterogeneity and injuries in AAA, and offered promising therapeutic intervention for AAA treatment.
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Conjugation of aptamers to homogeneous catalysts ("nucleoapzymes"), heterogeneous nanoparticle catalysts ("aptananozymes"), and photocatalysts ("photoaptazymes") yields superior catalytic/photocatalytic hybrid nanostructures emulating functions of native enzymes and photosystems. The concentration of the substrate in proximity to the catalytic sites ("molarity effect") or spatial concentration of electron-acceptor units in spatial proximity to the photosensitizers, by aptamer-ligand complexes, leads to enhanced catalytic/photocatalytic efficacies of the hybrid nanostructures. This is exemplified by sets of "nucleoapzymes" composed of aptamers conjugated to the hemin/G-quadruplex DNAzymes or metal-ligand complexes as catalysts, catalyzing the oxidation of dopamine to aminochrome, oxygen-insertion into the ArâH moiety of tyrosinamide and the subsequent oxidation of the catechol product into aminochrome, or the hydrolysis of esters or ATP. Also, aptananozymes consisting of aptamers conjugated to Cu2+ - or Ce4+ -ion-modified C-dots or polyadenine-stabilized Au nanoparticles acting as catalysts oxidizing dopamine or operating bioreactor biocatalytic cascades, are demonstrated. In addition, aptamers conjugated to the Ru(II)-tris-bipyridine photosensitizer or the Zn(II) protoporphyrin IX photosensitizer provide supramolecular photoaptazyme assemblies emulating native photosynthetic reaction centers. Effective photoinduced electron transfer followed by the catalyzed synthesis of NADPH or the evolution of H2 is demonstrated by the photosystems. Structure-function relationships dictate the catalytic and photocatalytic efficacies of the systems.
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Indolquinonas , Nanopartículas del Metal , Fármacos Fotosensibilizantes , Dopamina , Ligandos , Oro , Oligonucleótidos , CatálisisRESUMEN
BACKGROUND: It is controversial whether prophylactic endotracheal intubation (PEI) protects the airway before endoscopy in critically ill patients with upper gastrointestinal bleeding (UGIB). The study aimed to explore the predictive value of PEI for cardiopulmonary outcomes and identify high-risk patients with UGIB undergoing endoscopy. METHODS: Patients undergoing endoscopy for UGIB were retrospectively enrolled in the eICU Collaborative Research Database (eICU-CRD). The composite cardiopulmonary outcomes included aspiration, pneumonia, pulmonary edema, shock or hypotension, cardiac arrest, myocardial infarction, and arrhythmia. The incidence of cardiopulmonary outcomes within 48 h after endoscopy was compared between the PEI and non-PEI groups. Logistic regression analyses and propensity score matching analyses were performed to estimate effects of PEI on cardiopulmonary outcomes. Moreover, restricted cubic spline plots were used to assess for any threshold effects in the association between baseline variables and risk of cardiopulmonary outcomes (yes/no) in the PEI group. RESULTS: A total of 946 patients were divided into the PEI group (108/946, 11.4%) and the non-PEI group (838/946, 88.6%). After propensity score matching, the PEI group (n=50) had a higher incidence of cardiopulmonary outcomes (58.0% vs. 30.3%, P=0.001). PEI was a risk factor for cardiopulmonary outcomes after adjusting for confounders (odds ratio [OR] 3.176, 95% confidence interval [95% CI] 1.567-6.438, P=0.001). The subgroup analysis indicated the similar results. A shock index >0.77 was a predictor for cardiopulmonary outcomes in patients undergoing PEI (P=0.015). The probability of cardiopulmonary outcomes in the PEI group depended on the Charlson Comorbidity Index (OR 1.465, 95% CI 1.079-1.989, P=0.014) and shock index >0.77 (compared with shock index ≤0.77 [OR 2.981, 95% CI 1.186-7.492, P=0.020, AUC=0.764]). CONCLUSION: PEI may be associated with cardiopulmonary outcomes in elderly and critically ill patients with UGIB undergoing endoscopy. Furthermore, a shock index greater than 0.77 could be used as a predictor of a worse prognosis in patients undergoing PEI.
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Hydrochar from agricultural wastes is regarded as a prospective and low-cost material to activate peroxymonosulfate (PMS) for degrading pollutants. Herein, a novel in-situ N-doped hydrochar composite (RHCM4) was synthesized using montmorillonite and waste reed straw rich in nitrogen as pyrolysis catalyst and carbon source, respectively. The fabricated RHCM4 possessed excellent PMS activation performance for decomposing quinclorac (QC), a refractory herbicide, with a high removal efficiency of 100.0% and mineralization efficiency of 75.1%. The quenching experiments and electron spin resonance (ESR) detection disclosed free radicals (â¢OH, â¢SO4-, and â¢O2-) and non-radicals (1O2) took part in the QC degradation process. Additionally, the catalytic mechanisms were analyzed in depth with the aid of various characterizations. Moreover, the QC degradation intermediates and pathways were clarified by density functional theory calculations and HPLC-MS. Importantly, phytotoxicity experiments showed that RHCM4/PMS could efficaciously mitigate the injury of QC to Solanaceae crops (pepper, tomato, and tobacco). These findings give a new idea for enhancing the catalytic activity of hydrochar from agricultural wastes and broaden its application in the field of agricultural environment.
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Solanaceae , Estudios Prospectivos , Peróxidos , VerdurasRESUMEN
The aim of this study was to investigate the association between serum uric acid (UA) levels and hypertension in American individuals 20 years of age and older. We used continuous cross-sectional surveys from the National Health and Nutrition Examination Survey in the United States from 2007 to 2016. Our selected population was adults aged 20 years and older in the United States. We examined the association between serum UA and risk of hypertension using weighted univariate logistic regression analysis, weighted multivariate logistic regression analysis, weighted subgroup analysis, and weighted restricted cubic spline analysis. Serum UA was significantly linked with hypertension in a multivariate logistic regression model adjusted for all variables (odds ratio [OR]: 1.22, 95% confidence interval [CI]: 1.15-1.28, P < .001). Furthermore, dividing serum UA into quartiles (Q) revealed an association between elevated serum UA and increased risk of hypertension [Q1 = (OR: 1.00), Q2 = (OR: 1.13, 95% CI: 0.95-1.37, P = .159), Q3 = OR: 1.30, 95% CI: 1.10-1.52, P = .002), Q4 = OR: 1.94, 95% CI: 1.58-2.38, P = .161). Additionally, we conducted subgroup analyses for age, sex, race, education, marital status, diabetes status, smoking, and alcohol use and discovered that these factors had a moderating effect on serum UA and hypertension (P < .05). Last but not least, we looked into the nonlinear link between serum UA and hypertension using weighted restricted cubic splines and discovered that there was no such relationship. The segmental effect of serum UA and hypertension, with an inflection point of 5.079 (mg/dL), was discovered in our gender-stratified study. And in analyses stratified by race and marital status, we similarly found a dose-response relationship between UA and hypertension among Hispanics and unmarried people. Our study showed a positive correlation between serum UA and hypertension.
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Hipertensión , Ácido Úrico , Adulto , Humanos , Adulto Joven , Estudios Transversales , Encuestas Nutricionales , Hipertensión/epidemiología , Consumo de Bebidas AlcohólicasRESUMEN
Glucose oxidase-loaded ZIF-90 metal-organic framework nanoparticles conjugated to hemin-G-quadruplexes act as functional bioreactor hybrids operating transient dissipative biocatalytic cascaded transformations consisting of the glucose-driven H2O2-mediated oxidation of Amplex-Red to resorufin or the glucose-driven generation of chemiluminescence by the H2O2-mediated oxidation of luminol. One system involves the fueled activation of a reaction module leading to the temporal formation and depletion of the bioreactor conjugate operating the nickase-guided transient biocatalytic cascades. The second system demonstrates the fueled activation of a reaction module yielding a bioreactor conjugate operating the exonuclease III-dictated transient operation of the two biocatalytic cascades. The temporal operations of the bioreactor circuits are accompanied by kinetic models and computational simulations enabling us to predict the dynamic behavior of the systems subjected to different auxiliary conditions.
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Técnicas Biosensibles , ADN Catalítico , G-Cuádruplex , Estructuras Metalorgánicas , Nanopartículas , Glucosa Oxidasa/metabolismo , Peróxido de Hidrógeno , Glucosa , Reactores Biológicos , HeminaRESUMEN
DNA frameworks, consisting of constitutional dynamic networks (CDNs) undergoing fuel-driven reconfiguration, are coupled to a dissipative reaction module that triggers the reconfigured CDNs into a transient intermediate CDNs recovering the parent CDN state. Biocatalytic cascades consisting of the glucose oxidase (GOx)/horseradish peroxidase (HRP) couple or the lactate dehydrogenase (LDH)/nicotinamide adenine dinucleotide (NAD+) couple are tethered to the constituents of two different CDNs, allowing the CDNs-guided operation of the spatially confined GOx/HRP or LDH/NAD+ biocatalytic cascades. By applying two different fuel triggers, the directional transient CDN-guided upregulation/downregulation of the two biocatalytic cascades are demonstrated. By mixing the GOx/HRP-biocatalyst-modified CDN with the LDH/NAD+-biocatalyst-functionalized CDN, a composite CDN is assembled. Triggering the composite CDN with two different fuel strands results in orthogonal transient upregulation of the GOx/HRP cascade and transient downregulation of the LDH/NAD+ cascade or vice versa. The transient CDNs-guided biocatalytic cascades are computationally simulated by kinetic models, and the computational analyses allow the prediction of the performance of transient biocatalytic cascades under different auxiliary conditions. The concept of orthogonally triggered temporal, transient, biocatalytic cascades by means of CDN frameworks is applied to design an orthogonally operating CDN for the temporal upregulated or downregulated transient thrombin-induced coagulation of fibrinogen to fibrin.
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ADN Catalítico , ADN Catalítico/metabolismo , NAD , ADN , Biocatálisis , Glucosa Oxidasa/metabolismoRESUMEN
In this work, the orderly aggregated catalytic hairpin assembly (OA-CHA) was developed for synchronous ultrasensitive detection and high-efficiency colocalization imaging of dual-miRNAs by a carefully designed tetrahedral conjugated ladder DNA structure (TCLDS). Exactly, two diverse hairpin probes were fixed on tetrahedron conjugated DNA nanowires to form the TCLDS without fluorescence response, which triggered OA-CHA in the aid of output DNA 1 and output DNA 2 produced by targets miRNA-217 and miRNA-196a cycle to generate TCLDS with remarkable fluorescence response. Impressively, compared with the traditional CHA strategy, OA-CHA avoided the fluorescence group and quenching group from approaching again because of the spatial confinement effect to significantly enhance the fluorescence signal, resulting in the simultaneous ultrasensitive detection of dual-miRNAs with detection limits of 21 and 32 fM for miRNA-217 and miRNA-196a, respectively. Meanwhile, the TCLDS with lower diffusivity could achieve accurate localization imaging for reflecting the spatial distribution of dual-miRNAs in living cells. The strategy based on OA-CHA provided a flexible and programmable nucleic amplification method for the synchronous ultrasensitive detection and precise imaging of multiple biomarkers and had potential in disease diagnostics..
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Técnicas Biosensibles , ADN Catalítico , MicroARNs , MicroARNs/genética , Técnicas Biosensibles/métodos , ADN/química , Diagnóstico por Imagen , Catálisis , Límite de DetecciónRESUMEN
Purpose: Several existing studies have revealed that the occurrence of lichen planus (LP) is relevant to the gut microbiota, and the causal relationship between gut microbiota and LP was analyzed using the Mendelian randomization (MR) method. Methods: Through the two-sample MR method, single nucleotide polymorphisms (SNPs) relevant to gut microbiota were selected as instrument variables (IVs) to evaluate the causal association between gut microbiota and the risk of LP. Results: According to the selection criteria of inverse-variance weighted (IVW), six bacterial genera were found to be significantly linked to the initiation of LP; The IVW results suggested that Oxalobacteraceae, Victivallaceae, and Actinobacteria could restrain the initiation of LP, showing protective effects against LP. Desulfovibrio, Veillonella, and Ruminococcus gauvreauii groups were demonstrated to have casual correlations with the onset of LP. Conclusion: The relationship between gut microbiota and LP was not a single positive or inverse relationship. Investigation of the causal relationship of these gut microbiota with LP could further provide evidence for the intestine-skin axis theory. However, the specific mechanism of microorganisms affecting the skin remains to be clarified. In this paper, the protective effects and mechanisms of Oxalobacteraceae, Victivallaceae, and Actinobacteria on LP require further exploration.
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The combination of gene therapy and immunotherapy concepts, along recent advances in DNA nanotechnology, have the potential to provide important tools for cancer therapies. We present the development of stimuli-responsive microcapsules, loaded with a viral immunogenetic agent, harnessing the immune response against the Coronavirus Disease 2019, COVID-19, to selectively attack liver cancer cells (hepatoma) or recognize breast cancer or hepatoma, by expression of green fluorescence protein, GFP. The pH-responsive microcapsules, modified with DNA-tetrahedra nanostructures, increased hepatoma permeation by 50 %. Incorporation of a GFP-encoding lentivirus vector inside the tumor-targeting pH-stimulated miRNA-triggered and Alpha-fetoprotein-dictated microcapsules enables the demonstration of neoplasm selectivity, with approximately 5,000-, 8,000- and 50,000-fold more expression in the cancerous cells, respectively. The incorporation of the SARS-CoV-2 spike protein in the gene vector promotes specific recognition of the immune-evading hepatoma by the COVID-19-analogous immune response, which leads to cytotoxic and inflammatory activity, mediated by serum components taken from vaccinated or recovered COVID-19 patients, resulting in effective elimination of the hepatoma (>85 % yield).