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Cascade molecular events in complex systems are of vital importance for enhancing molecular diagnosis and information processing. However, the conversion of a cascaded biosensing system into a multilayer encrypted molecular keypad lock remains a significant challenge in the development of molecular logic devices. In this study, we present a photocleavable DNA nanotube-based dual-amplified resonance Rayleigh scattering (RRS) system for detecting microRNA-126 (miR-126). The cascading dual-amplification biosensing system provides a multilayer-encrypted prototype with the functionality of a molecular computing cascade keypad lock. RRS signals were greatly amplified by using photocleavable DNA nanotubes and enzyme-assisted strand displacement amplification (SDA). In the presence of miR-126, enzyme-assisted SDA produced numerous identical nucleotide fragments as the target, which were then specifically attached to magnetic beads through the DNA nanotube by using a Y-shaped DNA scaffold. Upon ultraviolet irradiation, the DNA nanotube was released into the solution, resulting in an increase in the intensity of the RRS signal. This strategy demonstrated a low limit of detection (0.16 fM) and a wide dynamic range (1 fM to 1 nM) for miR-126. Impressively, the enzyme-assisted SDA offers a molecular computing model for generating the target pool, which serves as the input element for unlocking the system. By cascading the molecular computing process, we successfully constructed a molecular keypad lock with a multilevel authentication technique. The proposed system holds great potential for applications in molecular diagnosis and information security, indicating significant value in integrating molecular circuits for intelligent sensing.
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Keratin and lipid structures in the stratum corneum (SC) are closely related to the SC barrier function. The application of penetration enhancers (PEs) disrupts the structure of SC, thereby promoting infiltration. To quantify these PE-induced structural changes in SC, we used confocal Raman imaging (CRI) and polarized Raman imaging (PRI) to explore the integrity and continuity of keratin and lipid structures in SC. The results showed that water is the safest PE and that oleic acid (OA), sodium dodecyl sulfate (SDS), and low molecular weight protamine (LMWP) disrupted the ordered structure of keratin, while azone and liposomes had less of an effect on keratin. Azone, OA, and SDS also led to significant changes in lipid structure, while LMWP and liposomes had less of an effect. Establishing this non-invasive and efficient strategy will provide new insights into transdermal drug delivery and skin health management.
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Liposomas , Piel , Liposomas/farmacología , Epidermis , Ácido Oléico/farmacología , QueratinasRESUMEN
BACKGROUND: Malnutrition is related to impaired oral health and function that causes poor dietary intake, declining the general health of older adults. The role of dietary intake in the association between oral function and nutritional status of Chinese older adults (aged 75 and above) was examined in this cross-sectional study. METHODS: Through the randomized cluster sampling method, 267 older adults living in rural areas of Qingdao, Shandong (aged 81.4 ± 4.3, 75-94 years) were chosen as the primary research participants. A Mini Nutritional Assessment - Short Form was used to determine nutritional status, and Food Frequency Questionnaire and 24-hour Food Intake Recall were used to assess dietary intake. The oral function was evaluated by analyzing the teeth, oral problems, bite force, tongue pressure, lip sealing pressure, chewing function questionnaire, whole saliva flow rate, 10-Item Eating Assessment Tool, and water swallow test. RESULTS: Based on the MNA-SF score, it was divided into a well-nourished group and a malnutrition group, with the malnutrition group comprising 40.6% of participants. The participants in the malnutrition group showed a higher rate of xerostomia, lower bite force, tongue pressure, and lip sealing pressure, and higher Chewing Function Questionnaire and 10-Item Eating Assessment Tool scores. Furthermore, their plant fat, iron, cereals and potatoes, vegetables, fruits, and seafood intake were relatively low. The regression model indicated that exercise frequency, stroke, chewing and swallowing function, intake of vegetables and fruits were risk factors for nutritional status of older adults. CONCLUSION: Malnutrition was relatively common among the Chinese older adults aged 75 and above, and it was significantly correlated with exercise frequency, stroke, chewing and swallowing function, and intake of vegetables and fruits. Therefore, nutrition management should be carried out under the understanding and guidance of the oral function and dietary intake of the older adults.
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Estado Nutricional , Humanos , Estudios Transversales , Anciano , Masculino , Femenino , Anciano de 80 o más Años , China/epidemiología , Desnutrición/epidemiología , Salud Bucal/estadística & datos numéricos , Dieta/estadística & datos numéricos , Ingestión de Alimentos/fisiología , Encuestas y Cuestionarios , Evaluación NutricionalRESUMEN
BACKGROUND: The effectiveness of acupuncture for patients with chronic spontaneous urticaria (CSU), reported in a few small-scale studies, is not convincing. OBJECTIVE: To investigate whether acupuncture leads to better effects on CSU than sham acupuncture or waitlist control. DESIGN: A multicenter, randomized, sham-controlled trial. (Chinese Clinical Trial Registry: ChiCTR1900022994). SETTING: Three teaching hospitals in China from 27 May 2019 to 30 July 2022. PARTICIPANTS: 330 participants diagnosed with CSU. INTERVENTION: Participants were randomly assigned in a 1:1:1 ratio to receive acupuncture, sham acupuncture, or waitlist control over an 8-week study period (4 weeks for treatment and another 4 weeks for follow-up). MEASUREMENTS: The primary outcome was the mean change from baseline in the Weekly Urticaria Activity Score (UAS7) at week 4. Secondary outcomes included itch severity scores, self-rated improvement, and Dermatology Life Quality Index scores. RESULTS: The mean change in UAS7 (range, 0 to 42) for acupuncture from baseline (mean score, 23.5 [95% CI, 21.8 to 25.2]) to week 4 (mean score, 15.3 [CI, 13.6 to 16.9]) was -8.2 (CI, -9.9 to -6.6). The mean changes in UAS7 for sham acupuncture and waitlist control from baseline (mean scores, 21.9 [CI, 20.2 to 23.6] and 22.1 [CI, 20.4 to 23.8], respectively) to week 4 (mean scores, 17.8 [CI, 16.1 to 19.5] and 20.0 [CI, 18.3 to 21.6], respectively) were -4.1 (CI, -5.8 to -2.4) and -2.2 (CI, -3.8 to -0.5), respectively. The mean differences between acupuncture and sham acupuncture and waitlist control were -4.1 (CI, -6.5 to -1.8) and -6.1 (CI, -8.4 to -3.7), respectively, which did not meet the threshold for minimal clinically important difference. Fifteen participants (13.6%) in the acupuncture group and none in the other groups reported adverse events. Adverse events were mild or transient. LIMITATION: Lack of complete blinding, self-reported outcomes, limited generalizability because antihistamine use was disallowed, and short follow-up period. CONCLUSION: Compared with sham acupuncture and waitlist control, acupuncture produced a greater improvement in UAS7, although the difference from control was not clinically significant. Increased adverse events were mild or transient. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Science and Technology Department of Sichuan Province.
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Terapia por Acupuntura , Urticaria Crónica , Urticaria , Humanos , Terapia por Acupuntura/efectos adversos , Urticaria Crónica/terapia , Urticaria Crónica/etiología , China , Resultado del Tratamiento , Urticaria/terapia , Urticaria/etiologíaRESUMEN
Thiosulfate influences the bioreduction and migration transformation of arsenic (As) and iron (Fe) in groundwater environments. The aim of this study was to investigate the impact of microbially-mediated sulfur cycling on the bioreduction and interaction of As and Fe. Microcosm experiments were conducted, including bioreduction of thiosulfate, As(V), and Fe(III) by Citrobacter sp. JH012-1, as well as the influence of thiosulfate input at different initial arsenate concentrations on the bioreduction of As(V) and Fe(III). The results demonstrate that Citrobacter sp. JH012-1 exhibited strong reduction capabilities for thiosulfate, As(V), and Fe(III). Improving thiosulfate level promoted the bioreduction of Fe(III) and As(V). When 0, 0.1, 0.5, and 1â¯mM thiosulfate were added, Fe(III) was completely reduced within 9 days, 3 days, 1â¯day, and 0.5 days, simultaneously, 72.8%, 82.2%, 85.5%, and 90.0% of As(V) were reduced, respectively. The products of As(III) binding with sulfide are controlled by the ratio of As-S. When the initial arsenate concentration was 0.025â¯mM, the addition of thiosulfate resulted in the accumulation of soluble thioarsenite. However, when the initial arsenate level increased to 1â¯mM, precipitates of orpiment or realgar were formed. In the presence of both arsenic and iron, As(V) significantly inhibits the bioreduction of Fe(III). Under the concentrations of 0, 0.025, and 1â¯mM As(V), the reduction rates of Fe(III) were 100%, 91%, and 83%, respectively. In this scenario, the sulfide produced by thiosulfate reduction tends to bind with Fe(II) rather than As(III). Therefore, the competition of arsenic-iron and thiosulfate concentration should be considered to study the impact of thiosulfate on arsenic and iron migration and transformation in groundwater.
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Arsénico , Agua Subterránea , Hierro/análisis , Arsénico/metabolismo , Arseniatos , Tiosulfatos , Oxidación-Reducción , Sulfuros , Compuestos Férricos/metabolismoRESUMEN
Development of an activated ratiometric indicator that is specific to plasma membrane (PM) viscosity exhibits great application prospects in disease diagnosis and treatment but remains a great challenge. Herein, a photo-activated fluorescent probe (CQ-IC) was designed and prepared tactfully, which could analyze and real-time monitor the microenvironmental homeostasis of the PM based on a two-channel ratiometric imaging model. Interestingly, upon light irradiation, CQ-IC generates reactive oxygen species and thus increases the cellular viscosity, which increases two emission peaks at 480 and 610 nm. This work would propose a new strategy to sensor PM homeostasis and effectively guide the treatment of viscosity-related diseases among various physiological and pathological processes.
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A label-free addressable photoelectric immunosensor array was designed for the detection of amyloid ß-proteins based on magnetic separation and self-calibration strategies. In this paper, Na2Ti6O13 with a flower-like morphology was prepared by the hydrothermal method; after continuously combining Fe3O4 and CdS, it was endowed with magnetism and better photoelectric activity. Subsequently, a series of reactions occurred in the solution, and the magnetic separation method was used to enrich the target. On the other hand, the ITO glass was separated into eight sites (2 × 4) using magnets, and a light shield was utilized to prevent light exposure, resulting in addressable and continuous detection. After the uniform preparation of magnetic photoelectric materials and precise control of testing conditions, the relative errors among different sites have been effectively reduced. Moreover, incorporating a self-calibration strategy has allowed the sensor array to achieve greater accuracy. The proposed photoelectrochemical biosensor exhibits a good relationship with amyloid ß-protein ranging from 0.01 to 100 ng mL-1 with a limit of detection of 1.1 pg mL-1 and exhibits excellent specificity, reproducibility, and stability.
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Técnicas Biosensibles , Compuestos de Cadmio , Péptidos beta-Amiloides , Técnicas Biosensibles/métodos , Reproducibilidad de los Resultados , Calibración , Técnicas Electroquímicas/métodos , Sulfuros , Límite de Detección , Inmunoensayo/métodosRESUMEN
Conventional electrochemical detection of microRNA (miRNA) encounters issues of poor sensitivity and fixed dynamic range. Here, we report a DNA tile and invading stacking primer-assisted CRISPR-Cas12a multiple amplification strategy to construct an entropy-controlled electrochemical biosensor for the detection of miRNA with tunable sensitivity and dynamic range. To amplify the signal, a cascade amplification of the CRISPR-Cas12a system along with invading stacking primer signal amplification (ISPSA) was designed to detect trace amounts of miRNA-31 (miR-31). The target miR-31 could activate ISPSA and produce numerous DNAs, triggering the cleavage of the single-stranded linker probe (LP) that connects a methylene blue-labeled DNA tile with a DNA tetrahedron to form a Y-shaped DNA scaffold on the electrode. Based on the decrease of current, miR-31 can be accurately and efficiently detected. Impressively, by changing the loop length of the LP, it is possible to finely tune the entropic contribution while keeping the enthalpic contribution constant. This strategy has shown a tunable limit of detection for miRNA from 0.31 fM to 0.56 pM, as well as a dynamic range from â¼2200-fold to â¼270,000-fold. Moreover, it demonstrated satisfactory results in identifying cancer cells with a high expression of miR-31. Our strategy broadens the application of conventional electrochemical biosensing and provides a tunable strategy for detecting miRNAs at varying concentrations.
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Sistemas CRISPR-Cas , MicroARNs , Entropía , Sistemas CRISPR-Cas/genética , ADN/genética , Electrodos , MicroARNs/genéticaRESUMEN
Tunable detection of microRNA is crucial to meet the desired demand for sample species with varying concentrations in clinical settings. Herein, we present a DNA walker-based molecular circuit for the detection of miRNA-21 (miR-21) with tunable dynamic ranges and sensitivity levels ranging from fM to pM. The phosphate-activated fluorescence of UiO-66-NH2 metal-organic framework nanoparticles was used as label-free fluorescence tags due to their competitive coordination effect with the Zr atom, which significantly inhibited the ligand-to-metal charge transfer. To achieve a tunable detection performance for miR-21, the ultraviolet sensitive o-nitrobenzyl was induced as a photocleavable linker, which was inserted at various sites between the loop and the stem of the hairpin probe to regulate the DNA strand displacement reaction. The dynamic range can be precisely regulated from 700- to 67,000-fold with tunable limits of detection ranging from 2.5 fM to 36.7 pM. Impressively, a Boolean logic tree and complex molecular circuit were constructed for logic computation and cancer diagnosis in clinical blood samples. This intelligent biosensing method presents a powerful solution for converting complex biosensing systems into actionable healthcare decisions and will facilitate early disease diagnosis.
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Técnicas Biosensibles , Nanopartículas del Metal , Estructuras Metalorgánicas , MicroARNs , Nanopartículas , ADN , MicroARNs/genética , Técnicas Biosensibles/métodos , Límite de DetecciónRESUMEN
Organophosphate pesticides are used in agriculture due to their high effectiveness and low persistence in eradicating insects and pests. However, conventional detection methods encounter the limitation of undesired detection specificity. Thus, screening phosphonate-type organophosphate pesticides (OOPs) from their analogues, phosphorothioate organophosphate pesticides (SOPs), remains a challenge. Here, we reported a d-penicillamine@Ag/Cu nanocluster (DPA@Ag/Cu NCs)-based fluorescence assay to screen OOPs from 21 kinds of organophosphate pesticides, which can be used for logic sensing and information encryption. Acetylthiocholine chloride was enzymatically split by acetylcholinesterase (AChE) to produce thiocholine, which reduced the fluorescence of DPA@Ag/Cu NCs due to the transmission of electrons from DPA@Ag/Cu NCs donor to the thiol group acceptor. Impressively, OOPs acted as an AChE inhibitor and retained the high fluorescence of DPA@Ag/Cu NCs due to the stronger positive electricity of the phosphorus atom. Conversely, SOPs possessed weak toxicity to AChE, which led to low fluorescence intensity. By setting 21 kinds of organophosphate pesticides as the inputs and the fluorescence of the resulting products as the outputs, DPA@Ag/Cu NCs could serve as a fluorescent nanoneuron to construct Boolean logic tree and complex logic circuit for molecular computing. As a proof of concept, by converting the selective response patterns of DPA@Ag/Cu NCs into binary strings, molecular crypto-steganography for encoding, storing, and concealing information was successfully achieved. This study is expected to advance the progress and practical application of nanoclusters in the area of logic detection and information security while also enhancing the relationship between molecular sensors and the world of information.
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Antígenos de Grupos Sanguíneos , Insecticidas , Nanopartículas del Metal , Organofosfonatos , Plaguicidas , Penicilamina , Acetilcolinesterasa , Compuestos Organofosforados , Colorantes , Organofosfatos , Lógica , Cobre , Plaguicidas/análisisRESUMEN
BACKGROUND: Cancer stem cells are one fundamental reason for the high recurrence rate of hepatocellular carcinoma (HCC) and its resistance to treatment. This study explored the mechanism by which SOCS2-AS1 affects HCC cell stemness. METHODS: Stem cells of HCC cell lines Huh7 and SNU-398 were sorted as NANOG-positive by flow cytometry. Stem cell sphere formation ability was detected. Stem cell viability, migration, invasion, and apoptosis were assessed by colony formation assays, Transwell assays, wound-healing assays, and TUNEL assays, respectively. The binding sites for SOCS2-AS1, miR-454-3p, miR-454-3p, and CPEB1 mRNA were assessed by dual-luciferase reporter assays. Quantitative real-time PCR (qPCR) and Western blot studies were performed to evaluate gene expression levels. ChIP and EMSA assays were conducted to confirm that YY1 binds with the SOCS2-AS1 promoter. A subcutaneous xenograft model was used to verify results in vivo. Tumor tissues were analyzed by H&E and TUNEL staining. RESULTS: SOCS2-AS1 was expressed at low levels in NANOG+ HCC stem cells, and HCC patients with a high level of SOCS2-AS1 expression had a higher survival rate. SOCS2-AS1 inhibited HCC cell stemness, migration, and invasion, and increased the cisplatin sensitivity of HCC cells by regulating miR-454-3p/CPEB1. YY1 was confirmed as a transcription factor of SOCS2-AS1, and served to inhibit SOCS2-AS1 transcription. YY1 knockdown suppressed HCC stemness via SOCS2-AS1. The role of SOCS2-AS1 was confirmed in a subcutaneous xenograft model, and SOCS2-AS1 overexpression enhanced the inhibitory effect of cisplatin on HCC in vivo. CONCLUSIONS: YY1-regulated lncRNA SOCS2-AS1 suppresses HCC cell stemness and progression via miR-454-3p/CPEB1.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , ARN Largo no Codificante , Humanos , Carcinoma Hepatocelular/patología , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Hepáticas/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Cisplatino , Línea Celular Tumoral , Células Madre Neoplásicas/patología , Regulación Neoplásica de la Expresión Génica , Proliferación Celular/genética , Movimiento Celular/genética , Proteínas Supresoras de la Señalización de Citocinas/genética , Proteínas Supresoras de la Señalización de Citocinas/metabolismo , Factores de Transcripción/metabolismo , Factores de Escisión y Poliadenilación de ARNm/genéticaRESUMEN
Heart failure (HF) is associated with multiple organ dysfunction and many comorbidities. Its incidence is high among the elderly and is a major health burden worldwide. Cognitive impairment (CI) is highly prevalent in older patients with HF, which is an abnormality in one or more of the items of cognition, attention, memory, language, psychomotor function, and visual spatial acuity. Studies have shown that the incidence of CI in HF patients is between 13 and 54%, and patients with both conditions have poor self-care ability and prognosis, as well as increased mortality rates. However, the mechanisms of CI development in HF patients are still unclear. In this review, we describe the epidemiology and risk factors as well as measures of improving CI in HF patients. We update the latest pathophysiological mechanisms related to the neurocognitive changes in HF patients, expounding on the mechanisms associated with the development of CI in HF patients.
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Trastornos del Conocimiento , Disfunción Cognitiva , Insuficiencia Cardíaca , Humanos , Anciano , Trastornos del Conocimiento/epidemiología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/psicología , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Cognición/fisiología , Comorbilidad , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/terapiaRESUMEN
We put forward a novel method for producing ultrarelativistic high-density high-polarization positrons through a single-shot interaction of a strong laser with a tilted solid foil. In our method, the driving laser ionizes the target, and the emitted electrons are accelerated and subsequently generate abundant γ photons via the nonlinear Compton scattering, dominated by the laser. These γ photons then generate polarized positrons via the nonlinear Breit-Wheeler process, dominated by a strong self-generated quasistatic magnetic field B^{S}. We find that placing the foil at an appropriate angle can result in a directional orientation of B^{S}, thereby polarizing positrons. Manipulating the laser polarization direction can control the angle between the γ photon polarization and B^{S}, significantly enhancing the positron polarization degree. Our spin-resolved quantum electrodynamics particle-in-cell simulations demonstrate that employing a laser with a peak intensity of about 10^{23} W/cm^{2} can obtain dense (â³10^{18} cm^{-3}) polarized positrons with an average polarization degree of about 70% and a yield of above 0.1 nC per shot. Moreover, our method is feasible using currently available or upcoming laser facilities and robust with respect to the laser and target parameters. Such high-density high-polarization positrons hold great significance in laboratory astrophysics, high-energy physics, and new physics beyond the standard model.
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Although the CRISPR/Cas system has pioneered a new generation of analytical techniques, there remain many challenges in developing a label-free, accurate, and reliable CRISPR/Cas-based assay for reporting the levels of low abundance biomolecules in complex biological samples. Here, we reported a novel CRISPR-derived resonance Rayleigh scattering (RRS) amplification strategy and logical circuit based on a guanine nanowire (G-wire) assisted non-cross-linking hybridization chain reaction (GWancHCR) for label-free detection of lipopolysaccharide (LPS). In the presence of a target, the protospacer-adjacent motif-inserted aptamer is rationally designed to specifically combine with LPS rather than Cas12a, suppressing the trans-cleavage activity of CRISPR/Cas12a and retaining the reporter probes to trigger non-cross-linking aggregation. Owing to the automatic hybridization chain reaction (HCR), in the presence of Mg2+, the released G-quadruplex sequence aggregated to assemble the G-wire superstructure through non-cross-linking. As a result, a dramatically amplified RRS intensity is observed, allowing for reporting LPS levels in a low detection limit of 0.17 pg/mL and a wide linear range among 1.0-100.0 ng/mL. Moreover, this reaction event is capable of programming to perform classical Boolean logic tree analysis, including basic logic computing and complex integrated logic circuits. This study comprehensively analyzed with respect to information flow, matter (molecular events), and energy (RRS), revealing the potential promise in designing of molecular-level "Internet of Things", intelligent computing, and sensing systems.
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Nanocables , Sistemas CRISPR-Cas/genética , Guanina , Lipopolisacáridos , LógicaRESUMEN
The development of facile, reliable, and accurate assays for pathogenic bacteria is critical to environmental pollution surveillance, traceability analysis, prevention, and control. Here, we proposed a rolling circle amplification (RCA) strategy-driven visual photothermal smartphone-based biosensor for achieving highly sensitive monitoring of Escherichia coli (E. coli) in environmental media. In this design, E. coli could specifically bind with its recognition aptamer for initiating the RCA process on a magnetic bead (MB). Owing to the cleaving of UV irradiation toward photoresponsive DNA on MB, the RCA products were released to further hybridize with near-infrared excited CuxS-modified DNA probes. As a result, the photothermal signal was enhanced by RCA, while the background was decreased by UV irradiation and magnetic separation. The correspondingly generated photothermal signals were unambiguously recorded on a smartphone, allowing for an E. coli assay with a low detection limit of 1.8 CFU/mL among the broad linear range from 5.0 to 5.0 × 105 CFU/mL. Significantly, this proposed biosensor has been successfully applied to monitor the fouling levels of E. coli in spring water samples with acceptable results. This study holds great prospects by integrating a RCA-driven photothermal amplification strategy into a smartphone to develop accurate, reliable, and efficient analytical platforms against pathogenic bacteria pollutions for safeguarding environmental health.
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Técnicas Biosensibles , Infecciones por Escherichia coli , Humanos , Escherichia coli/genética , Escherichia coli/metabolismo , Técnicas de Amplificación de Ácido Nucleico/métodos , Técnicas Biosensibles/métodos , ADN/genética , Fenómenos Magnéticos , Límite de DetecciónRESUMEN
Circularly polarized (CP) γ-ray sources are versatile for broad applications in nuclear physics, high-energy physics, and astrophysics. The laser-plasma based particle accelerators provide accessibility for much higher flux γ-ray sources than conventional approaches, in which, however, the circular polarization properties of the emitted γ-photons are usually neglected. In this Letter, we show that brilliant CP γ-ray beams can be generated via the combination of laser plasma wakefield acceleration and plasma mirror techniques. In a weakly nonlinear Compton scattering scheme with moderate laser intensities, the helicity of the driving laser can be transferred to the emitted γ-photons, and their average polarization degree can reach â¼61% (20%) with a peak brilliance of â³1021 photons/(s · mm2 · mrad2 · 0.1% BW) around 1 MeV (100 MeV). Moreover, our proposed method is easily feasible and robust with respect to the laser and plasma parameters.
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BACKGROUND AND AIMS: Our previous studies demonstrated that 2-octynoic acid (2OA) might alter the conformational structure of the inner lipoic acid (LA) binding domain (ILD) in the E2 subunit of pyruvate dehydrogenase complex (PDC-E2), leading to the loss of immune tolerance in simple primary biliary cholangitis (S-PBC). Here, we further explore if this etiological mechanism also accounts for connective tissue disease-associated PBC (CTD-PBC). METHODS: Intein-mediated protein ligation was used to prepare ILD, LA-ILD and 2OA-ILD, and their reactivity with serum samples from 124 S-PBC and 132 CTD-PBC patients was examined. The antibodies to LA, 2OA, LA-ILD and 2OA-ILD, the isotypes of antibodies to LA, 2OA and ILD, were comparatively detected between the two patient groups by enzyme-linked immunosorbent assay and immunoblotting. RESULTS: Both the percentage and reactivity of antibody to 2OA in S-PBC were significantly higher than in CTD-PBC. Antibodies to 2OA and to LA between the two groups separately shared the same characteristics. Remarkably, coexistence of the antibodies to LA-ILD and to 2OA, and coexistence of the antibodies to LA and to 2OA in S-PBC were both significantly more frequent than in CTD-PBC, whereas the percentage of anti-LA antibody without anti-2OA antibody in S-PBC was markedly lower than in CTD-PBC. Moreover, the isotype of antibody to LA was predominantly IgG in CTD-PBC, whilst this isotype was mainly IgM in S-PBC. CONCLUSION: Xenobiotic 2OA might play less important pathogenic role in CTD-PBC than in S-PBC, suggesting that different underlying mechanisms are involved in their immune intolerance to PDC-E2.
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Colangitis , Enfermedades del Tejido Conjuntivo , Cirrosis Hepática Biliar , Autoanticuerpos , Colangitis/complicaciones , Enfermedades del Tejido Conjuntivo/complicaciones , Humanos , Inmunidad , Xenobióticos/metabolismoRESUMEN
Although the preparation of nano-objects by emulsifier-free controlled/living radical emulsion polymerization has drawn much attention, the morphologies of these formed objects are difficult to predict and to reproduce because of the much more complex nucleation mechanisms of emulsion polymerization compared to only one self-assembling nucleation mechanism of controlled radical dispersion polymerization. The present study compares dispersion polymerization with emulsifier-free emulsion polymerization in terms of nucleation mechanism, polymerization kinetics, and disappearance behavior of the macrochain transfer agent, gel permeation chromatograms curves of the obtained block copolymer as well as the structural and morphological differences between the produced nano-objects on the basis of published data. Moreover, the effects of the inherently heterogeneous nature of emulsion polymerization on the mechanism of reversible addition-fragmentation transfer polymerization and the nano-object morphology are examined, and efficient agitation and adequate solubility of the core-forming monomer in water are identified as the most crucial factors for the fabrication of nonspherical nano-objects.
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Polímeros , Agua , Emulsiones , Cinética , PolimerizacionRESUMEN
BACKGROUND: Pneumonia is a serious pediatric lung injury disease caused by Mycoplasma pneumoniae (M. pneumoniae) with increasing global prevalence every year. The WHO has reported that nearly 19% of children die due to pneumonia worldwide. OBJECTIVE: The present research was conducted to discover the ameliorative properties of geraniol against M. pneumoniae-provoked pneumonia in mice through the modulation of inflammatory responses. METHODOLOGY: The pneumonia was provoked in the male Swiss albino mice via infecting animals with 100 µl of M. pneumoniae for 2 days and supplemented concurrently with 20 mg/kg of geraniol for 3 days. 100 mg/kg of azithromycin was used as a standard drug. The nitric oxide (NO) level and MPO activity were measured using kits. The SOD activity, GSH, and MDA levels were studied using standard methods. The polymerase chain reaction (PCR) study was performed to examine the M. pneumoniae DNA load. The inflammatory cytokines status was assessed by assay kits. The ERK1/2, JNK1/2, and NF-κB expressions were studied by reverse-transcription (RT-PCR). The lung tissues were analyzed microscopically to investigate the histological alterations. RESULTS: Geraniol treatment effectively reduced lung weight, NO level, and MPO activity in the pneumonia mice. The total cells and M. pneumoniae DNA load were also decreased by the geraniol. The SOD activity and GSH level were improved and MDA was decreased by the geraniol treatment. The IL-1, IL-6, IL-8, TNF-α, and TGF status were appreciably depleted by the geraniol in the pneumonia mice. Geraniol also suppressed the ERK1/2 and NF-κB expressions in the lung tissues. Histological findings also suggest the therapeutic roles of geraniol against pneumonia in mice. CONCLUSION: In summary, our results proved the beneficial roles of geraniol against the M. pneumoniae-provoked pneumonia. Geraniol could be a hopeful therapeutic agent to treat pneumonia in the future.
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Lesión Pulmonar , Neumonía por Mycoplasma , Monoterpenos Acíclicos , Animales , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Pulmón/metabolismo , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/etiología , Lesión Pulmonar/metabolismo , MAP Quinasa Quinasa 4/metabolismo , Masculino , Ratones , Mycoplasma pneumoniae/metabolismo , FN-kappa B/metabolismo , Neumonía por Mycoplasma/tratamiento farmacológico , Neumonía por Mycoplasma/metabolismo , Transducción de Señal , Superóxido Dismutasa/metabolismoRESUMEN
BACKGROUND AND OBJECTIVES: Energy provided by macronutrients plays a key role in healthy aging. This study therefore explored the association between macronutrients and cognitive function in elderly populations in rural areas of Qingdao, China. METHODS AND STUDY DESIGN: This study included 1,504 participants over the age of 65 recruited from Licha Town, Qingdao City, China. Dietary intake was measured using the Food Frequency Questionnaire, and cognitive function was assessed using the Mini-Mental State Examination. Logistic regression models were used to evaluate the association between dietary macronutrient intake and cognitive function. In addition, restricted cubic bars were applied to determine the dose-response relationship between macronutrient ratios and cognitive performance. RESULTS: A total of 877 adults over the age of 65 were included. After adjusting the weighted multiple variables, significant positive associations were revealed between protein and moderate carbohydrate intake and cognitive ability, but a negative association between fat intake and cognitive performance was identified. After calculating the daily energy supply ratio, similar associations were revealed between fat and protein intake and cognitive function. Furthermore, the ratio of proteins to carbohydrates had a U-shaped relationship with cognitive function (pnonlinearity=0.674), whereas the ratio of proteins to fats was L-shaped with lower cognitive function (pnonlinearity<0.001). Compared with the lowest quartile of the ratio of protein to fat intake, the weighted adjusted OR (95% CI) of the highest quartile was 0.509 (0.314, 0.827) for low cognitive performance. CONCLUSIONS: With an adequate carbohydrate supply, appropriately increasing dietary protein intake and reducing fat intake might benefit the cognitive function of elders in rural areas.