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Epigenetic dysregulation that leads to alterations in gene expression and is suggested to be one of the key pathophysiological factors of Parkinson's disease (PD). Here, we found that α-synuclein preformed fibrils (PFFs) induced histone H3 dimethylation at lysine 9 (H3K9me2) and increased the euchromatic histone methyltransferases EHMT1 and EHMT2, which were accompanied by neuronal synaptic damage, including loss of synapses and diminished expression levels of synaptic-related proteins. Furthermore, the levels of H3K9me2 at promoters in genes that encode the synaptic-related proteins SNAP25, PSD95, Synapsin 1 and vGLUT1 were increased in primary neurons after PFF treatment, which suggests a linkage between H3K9 dimethylation and synaptic dysfunction. Inhibition of EHMT1/2 with the specific inhibitor A-366 or shRNA suppressed histone methylation and alleviated synaptic damage in primary neurons that were treated with PFFs. In addition, the synaptic damage and motor impairment in mice that were injected with PFFs were repressed by treatment with the EHMT1/2 inhibitor A-366. Thus, our findings reveal the role of histone H3 modification by EHMT1/2 in synaptic damage and motor impairment in a PFF animal model, suggesting the involvement of epigenetic dysregulation in PD pathogenesis.
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Trastornos Motores , Enfermedad de Parkinson , Animales , Ratones , Histonas/metabolismo , Metilación , Neuronas/metabolismo , alfa-Sinucleína/metabolismoRESUMEN
4H-silicon carbide (4H-SiC) possesses a high Baliga figure of merit, making it a promising material for power electronics. However, its applications are limited by low hole mobility. Herein, we found that the hole mobility of 4H-SiC is mainly limited by the strong interband electron-phonon scattering using mode-level first-principles calculations. Our research indicates that applying compressive strain can reverse the sign of crystal-field splitting and change the ordering of electron bands close to the valence band maximum. Therefore, the interband electron-phonon scattering is severely suppressed and the electron group velocity is significantly increased. The out-of-plane hole mobility of 4H-SiC can be greatly enhanced by â¼200% with 2% uniaxial compressive strain applied. This work provides new insights into the electron transport mechanisms in semiconductors and suggests a strategy to improve hole mobility that could be applied to other semiconductors with hexagonal crystalline geometries.
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Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by pulmonary and systemic congestion resulting from left ventricular diastolic dysfunction and increased filling pressure. Currently, however, there is no evidence on effective pharmacotherapy for HFpEF. In this study, we aimed to investigate the therapeutic effect of total xanthones extracted from Gentianella acuta (TXG) on HFpEF by establishing an high-fat diet (HFD) + L-NAME-induced mouse model. Echocardiography was employed to assess the impact of TXG on the cardiac function in HFpEF mice. Haematoxylin and eosin staining, wheat germ agglutinin staining, and Masson's trichrome staining were utilized to observe the histopathological changes following TXG treatment. The results demonstrated that TXG alleviated HFpEF by reducing the expressions of genes associated with myocardial hypertrophy, fibrosis and apoptosis. Furthermore, TXG improved cardiomyocyte apoptosis by inhibiting the expression of apoptosis-related proteins. Mechanistic investigations revealed that TXG could activate the inositol-requiring enzyme 1α (IRE1α)/X-box-binding protein 1 (Xbp1s) signalling pathway, but the knockdown of IRE1α using the IRE1α inhibitor STF083010 or siRNA-IRE1α impaired the ability of TXG to ameliorate cardiac remodelling in HFpEF models. In conclusion, TXG alleviates myocardial hypertrophy, fibrosis and apoptosis through the activation of the IRE1α/Xbp1s signalling pathway, suggesting its potential beneficial effects on HFpEF patients.
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Apoptosis , Endorribonucleasas , Insuficiencia Cardíaca , Proteínas Serina-Treonina Quinasas , Transducción de Señal , Proteína 1 de Unión a la X-Box , Xantonas , Animales , Endorribonucleasas/metabolismo , Endorribonucleasas/genética , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Proteína 1 de Unión a la X-Box/metabolismo , Proteína 1 de Unión a la X-Box/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Transducción de Señal/efectos de los fármacos , Ratones , Masculino , Xantonas/farmacología , Xantonas/aislamiento & purificación , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Dieta Alta en Grasa/efectos adversos , Fibrosis , Volumen Sistólico/efectos de los fármacosRESUMEN
Soil salinization/alkalization is a complex environmental factor that includes not only neutral salt NaCl but also other components like Na2CO3. miRNAs, as small molecules that regulate gene expression post-transcriptionally, are involved in plant responses to abiotic stress. In this study, maize seedling roots were treated for 5 h with 100 mM NaCl, 50 mM Na2CO3, and H2O, respectively. Sequencing analysis of differentially expressed miRNAs under these conditions revealed that the Na2CO3 treatment group had the most differentially expressed miRNAs. Cluster analysis indicated their main involvement in the regulation of ion transport, binding, metabolism, and phenylpropanoid and flavonoid biosynthesis pathways. The unique differentially expressed miRNAs in the NaCl treatment group were related to the sulfur metabolism pathway. This indicates a significant difference in the response patterns of maize to different treatment groups. This study provides theoretical evidence and genetic resources for further analysis of the molecular mechanisms behind maize's salt-alkali tolerance.
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The ongoing development of ratiometric optical thermometry is mainly trapped in thermally coupled levels of rare-earth ions and inefficient ultraviolet excitation. Herein, a new-type multiple sharp line emitting, blue light-excited K2NaInF6:Mn4+, Eu3+ fluoride phosphor has been reported as a ratiometric thermometer. The f-f transition of Eu3+ paves a steady reference to a highly temperature sensitive Mn4+d-d transition and enables high relative sensitivity of 1.65% K-1 at 573â K. An optical fiber thermometry on a household oven with a relative standard deviation of 0.11% surpasses the standard of precision measurement, showing great potential in practical application. This discovery offers a highly sensitive neotype blue light-excitable ratiometric temperature sensor, that is Mn4+-doped fluoride, promoting practical applications of optical thermometry.
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The development of nanotherapy targeting mitochondria to alleviate oxidative stress is a critical therapeutic strategy for vascular calcification (VC) in diabetes. In this study, we engineered mitochondria-targeted nanodrugs (T4O@TPP/PEG-PLGA) utilizing terpinen-4-ol (T4O) as a natural antioxidant and mitochondrial protector, PEG-PLGA as the nanocarrier, and triphenylphosphine (TPP) as the mitochondrial targeting ligand. In vitro assessments demonstrated enhanced cellular uptake of T4O@TPP/PEG-PLGA, with effective mitochondrial targeting. This nanodrug successfully reduced oxidative stress induced by high glucose levels in vascular smooth muscle cells. In vivo studies showed prolonged retention of the nanomaterials in the thoracic aorta for up to 24 h. Importantly, experiments in diabetic VC models underscored the potent antioxidant properties of T4O@TPP/PEG-PLGA, as evidenced by its ability to mitigate VC and restore mitochondrial morphology. These results suggest that these nanodrugs could be a promising strategy for managing diabetic VC.
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Antioxidantes , Mitocondrias , Estrés Oxidativo , Calcificación Vascular , Animales , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Antioxidantes/farmacología , Antioxidantes/química , Calcificación Vascular/tratamiento farmacológico , Calcificación Vascular/metabolismo , Calcificación Vascular/patología , Estrés Oxidativo/efectos de los fármacos , Compuestos Organofosforados/química , Compuestos Organofosforados/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Nanopartículas/química , Ratones , Masculino , Polietilenglicoles/química , Ratas , Humanos , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismoRESUMEN
This article explores the asymmetric Michael addition reaction of 2-hydroxy-1,4-naphthoquinone and indole-3-ones catalyzed by cinchona alkaloids. This strategy utilizes 2-hydroxy-1,4-naphthoquinone and easily prepared indole-3-one as substrates, resulting in the synthesis of 23 unprecedented indolin-3-ones bearing a 1,4-naphthoquinone unit at the C2 position of indole under simple and mild reaction conditions, with up to 88% yield, 98% ee, and >20:1 dr.
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Chiral recognition of enantiomers with identical mirror-symmetric molecular structures is important for the analysis of biomolecules, and it conventionally relies on stereoselective interactions in chiral chemical environments. Here, we develop a magneto-electrochemical method for the enhanced detection of chiral amino acids (AAs), that combines the advantages of the high sensitivity of electrochemiluminescent (ECL) biosensors and chirality-induced effects under a magnetic field. The ECL difference between L- and D-enantiomers can be amplified over 35-fold under a field of 3.5 kG, and the chiral discrimination can be achieved in dilute AA solutions down to the nM level. The field-dependent ECL and chronocoulometry measurements suggest that chiral AAs can lock the spins on their radicals and thus enlarge the ECL change under applied magnetic fields (magneto-ECL, MECL), which explains the field-enhanced chiral discrimination of AA enantiomers. Finally, a detailed protocol is demonstrated for the identification of unknown AA solutions, in which the species, chirality and concentration of AAs can be determined simultaneously from the 2D plots of the ECL and MECL results. This work benefits the development of field-assisted detection methods and represents a promising and universal strategy for the comprehensive analysis of chiral biomolecules.
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Aminoácidos , Técnicas Electroquímicas , Estereoisomerismo , Aminoácidos/química , Técnicas Electroquímicas/métodos , Mediciones Luminiscentes/métodos , Técnicas Biosensibles/métodos , Campos Magnéticos , Límite de DetecciónRESUMEN
OBJECTIVES: Currently, most medical laboratories do not have a dedicated software for managing report recalls, and relying on traditional manual methods or laboratory information system (LIS) to record recall data is no longer sufficient to meet the quality management requirements in the large regional laboratory center. The purpose of this article was to describe the research process and preliminary evaluation results of integrating the Medical Laboratory Electronic Record System (electronic record system) laboratory report recall function into the iLab intelligent management system for quality indicators (iLab system), and to introduce the workflow and methods of laboratory report recall management in our laboratory. METHODS: This study employed cluster analysis to extract commonly used recall reasons from laboratory report recall records in the electronic record system. The identified recall reasons were validated for their applicability through a survey questionnaire and then incorporated into the LIS for selecting recall reasons during report recall. The statistical functionality of the iLab system was utilized to investigate the proportion of reports using the selected recall reasons among the total number of reports, and to perform visual analysis of the recall data. Additionally, we employed P-Chart to establish quality targets and developed a "continuous improvement process" electronic flow form. RESULTS: The reasons for the recall of laboratory reports recorded in the electronic recording system were analyzed. After considering the opinions of medical laboratory personnel, a total of 12 recall reasons were identified, covering 73.05â¯% (1854/2538) of the recalled laboratory reports. After removing data of mass spectra lab with significant anomalies, the coverage rate increased to 82.66â¯% (1849/2237). The iLab system can generate six types of statistical graphs based on user needs, including statistical time, specialty labs (or divisions), test items, reviewers, reasons for report recalls, and distribution of the recall frequency of 0-24 h reports. The control upper limit of the recall rate of P-Chart based on laboratory reports can provide quality targets suitable for each professional group at the current stage. Setting the five stages of continuous process improvement reasonably and rigorously can effectively achieve the goal of quality enhancement. CONCLUSIONS: The enhanced iLab system enhances the intelligence and sustainable improvement capability of the recall management of laboratory reports, thus improving the efficiency of the recall management process and reducing the workload of laboratory personnel.
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Sistemas de Información en Laboratorio Clínico , Registros Electrónicos de Salud , Humanos , Programas Informáticos , Laboratorios , Unidades HospitalariasRESUMEN
OBJECTIVE: In this study, we aimed to enhance the treatment protocols and help understand the harm caused by the accidental ingestion of magnetic beads by children. METHODS: Data were collected from 72 children with multiple gastrointestinal perforations or gastrointestinal obstructions. The 72 pediatric patients were divided into a perforation and a non-perforation group. The data collected for the analysis included the gender, age, medical history, place of residence (rural or urban), and symptoms along with the educational background of the caregiver, the location and quantity of any foreign bodies discovered during the procedure, whether perforation was confirmed during the procedure, and the number of times magnetic beads had been accidentally ingested. RESULTS: The accuracy rate of preoperative gastrointestinal perforation diagnosis via ultrasound was 71%, while that of the upright abdominal X-ray method was only 46%. In terms of symptoms, the risk of perforation was 13.844 and 12.703 times greater in pediatric patients who experienced vomiting and abdominal pain with vomiting and abdominal distension, respectively, compared to patients in an asymptomatic state. There were no statistical differences between the perforation and the non-perforation groups in terms of age, gender, medical history, and the number of magnetic beads ingested (P > 0.05); however, there were statistical differences in terms of white blood cell count (P = 0.048) and c-reactive protein levels (P = 0.033). A total of 56% of cases underwent a laparotomy along with perforation repair and 19% underwent gastroscopy along with laparotomy. All pediatric patients recovered without complications following surgery. CONCLUSION: Abdominal ultrasonography and/or upright abdominal X-ray analyses should be carried out as soon as possible in case of suspicion of accidental ingestion of magnetic beads by children. In most cases, immediate surgical intervention is required. Given the serious consequences of ingesting this type of foreign body, it is essential to inform parents and/or caregivers about the importance of preventing young children from using such products.
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Cuerpos Extraños , Tracto Gastrointestinal , Humanos , Niño , Preescolar , Tracto Gastrointestinal/cirugía , Cuerpos Extraños/diagnóstico por imagen , Cuerpos Extraños/cirugía , Cuerpos Extraños/complicaciones , Vómitos/etiología , Ingestión de Alimentos , Fenómenos MagnéticosRESUMEN
Collaborative crowdsensing is a team collaboration model that harnesses the intelligence of a large network of participants, primarily applied in areas such as intelligent computing, federated learning, and blockchain. Unlike traditional crowdsensing, user recruitment in collaborative crowdsensing not only considers the individual capabilities of users but also emphasizes their collaborative abilities. In this context, this paper takes a unique approach by modeling user interactions as a graph, transforming the recruitment challenge into a graph theory problem. The methodology employs an enhanced Prim algorithm to identify optimal team members by finding the maximum spanning tree within the user interaction graph. After the recruitment, the collaborative crowdsensing explored in this paper presents a challenge of unfair incentives due to users engaging in free-riding behavior. To address these challenges, the paper introduces the MR-SVIM mechanism. Initially, the process begins with a Gaussian mixture model predicting the quality of users' tasks, combined with historical reputation values to calculate their direct reputation. Subsequently, to assess users' significance within the team, aggregation functions and the improved PageRank algorithm are employed for local and global influence evaluation, respectively. Indirect reputation is determined based on users' importance and similarity with interacting peers. Considering the comprehensive reputation value derived from the combined assessment of direct and indirect reputations, and integrating the collaborative capabilities among users, we have formulated a feature function for contribution. This function is applied within an enhanced Shapley value method to assess the relative contributions of each user, achieving a more equitable distribution of earnings. Finally, experiments conducted on real datasets validate the fairness of this mechanism.
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Since the appearance of SARS-CoV-2 in 2019, the ensuing COVID-19 (Corona Virus Disease 2019) pandemic has posed a significant threat to the global public health system, human health, life, and economic well-being. Researchers worldwide have devoted considerable efforts to curb its spread and development. The latest studies have identified five viral proteins, spike protein (Spike), viral main protease (3CLpro), papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), and viral helicase (Helicase), which play crucial roles in the invasion of SARS-CoV-2 into the human body and its lifecycle. The development of novel anti-SARS-CoV-2 drugs targeting these five viral proteins holds immense promise. Therefore, the development of efficient, high-throughput screening methodologies specifically designed for these viral proteins is of utmost importance. Currently, a plethora of screening techniques exists, with fluorescence-based assays emerging as predominant contenders. In this review, we elucidate the foundational principles and methodologies underpinning fluorescence-based screening approaches directed at these pivotal viral targets, hoping to guide researchers in the judicious selection and refinement of screening strategies, thereby facilitating the discovery and development of lead compounds for anti-SARS-CoV-2 pharmaceuticals.
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COVID-19 , Humanos , SARS-CoV-2 , Proteínas Virales , Antivirales/uso terapéutico , Péptido HidrolasasRESUMEN
Nsp13, a non-structural protein belonging to the coronavirus family 1B (SF1B) helicase, exhibits 5'-3' polarity-dependent DNA or RNA unwinding using NTPs. Crucially, it serves as a key component of the viral replication-transcription complex (RTC), playing an indispensable role in the coronavirus life cycle and thereby making it a promising target for broad-spectrum antiviral therapies. The imidazole scaffold, known for its antiviral potential, has been proposed as a potential scaffold. In this study, a fluorescence-based assay was designed by labeling dsDNA substrates with a commercial fluorophore and monitoring signal changes upon Nsp13 helicase activity. Optimization and high-throughput screening validated the feasibility of this approach. In accordance with the structural characteristics of ADP, we employed a structural-based design strategy to synthesize three classes of imidazole-based compounds through substitution reaction. Through in vitro activity research, pharmacokinetic parameter analysis, and molecular docking simulation, we identified compounds A16 (IC50 = 1.25 µM) and B3 (IC50 = 0.98 µM) as potential lead antiviral compounds for further targeted drug research.
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Antivirales , Pruebas de Enzimas , Imidazoles , SARS-CoV-2 , Proteínas no Estructurales Virales , Humanos , Antivirales/farmacología , Antivirales/química , Tratamiento Farmacológico de COVID-19 , Colorantes Fluorescentes/química , Imidazoles/química , Imidazoles/farmacología , Metiltransferasas/antagonistas & inhibidores , Simulación del Acoplamiento Molecular , ARN Helicasas/antagonistas & inhibidores , SARS-CoV-2/enzimología , SARS-CoV-2/efectos de los fármacos , Proteínas no Estructurales Virales/antagonistas & inhibidores , Pruebas de Enzimas/métodosRESUMEN
The booming demand on data security has aroused great interest for developing smart materials with temporal display feature and dynamic multicolor fluorescence. However, it remains challenging to implement both features on most responsive molecules. Herein, we construct a polymer free volume-controlled "molecular clock and emitter" via covalently embedding a multi-stimuli responsive molecular switch (i.e., spiropyran) into a polymer network (i.e., poly(pentafluorophenyl acrylate)) with programmable crosslink density and free volume. By the aminolysis of pentafluorophenyl ester with different amount of diamine crosslinkers, pPFPA-co-SP networks with controllable crosslink densities are generated, which have different confinement effects on the rate constant of SP/MC isomerization, thus leading to time-dependent photochromism. In addition, PTF1, a fluorescent probe that is sensitive to polymer rigidity, is introduced to further endow pPFPA-co-SP system with phototunable dynamic full-color emission. Therefore, relying on their synergistical responses to the rigidity of the polymer network, we have successfully developed a versatile molecular clock and emitter via an "one stone two birds" manner, which shows time-dependent data display along with dynamic multicolor fluorescence switching, providing great potential for advanced encryption and anticounterfeiting with a high security level.
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The selectivity of multicarbon products in the CO2 reduction reaction (CO2RR) depends on the spin alignment of neighboring active sites, which requires a spin catalyst that facilitates electron transfer with antiparallel spins for enhanced C-C coupling. Here, we design a radical-contained spin catalyst (TEMPOL@HKUST-1) to enhance CO2-to-ethylene conversion, in which spin-disordered (SDO) and spin-ordered (SO) phases co-exist to construct an asymmetric spin configuration of neighboring active sites. The replacement of axially coordinated H2O molecules with TEMPOL radicals introduces spin-spin interactions among the Cu(II) centers to form localized SO phases within the original H2O-mediated SDO phases. Therefore, TEMPOL@HKUST-1 derived catalyst exhibited an approximately two-fold enhancement in ethylene selectivity during the CO2RR at -1.8â V versus Ag/AgCl compared to pristine HKUST-1. In situ ATR-SEIRAS spectra indicate that the spin configuration at asymmetric SO/SDO sites significantly reduces the kinetic barrier for *CO intermediate dimerization toward the ethylene product. The performance of the spin catalyst is further improved by spin alignment under a magnetic field, resulting in a maximum ethylene selectivity of more than 50 %. The exploration of the spin-polarized kinetics of the CO2RR provides a promising path for the development of novel spin electrocatalysts with superior performance.
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The development of a methodology for synthesizing value-added urea (CO(NH2)2) via a renewable electricity-driven C-N coupling reaction under mild conditions is highly anticipated. However, the complex catalytic active sites that act on the carbon and nitrogen species make the reaction mechanism unclear, resulting in a low efficiency of C-N coupling from the co-reduction of carbon dioxide (CO2) and nitrate (NO3 -). Herein, we propose a novel tandem catalyst of Mo-PCN-222(Co), in which the Mo sites serve to facilitate nitrate reduction to the *NH2 intermediate, while the Co sites enhance CO2 reduction to carbonic oxide (CO), thus synergistically promoting C-N coupling. The synthesized Mo-PCN-222(Co) catalyst exhibited a noteworthy urea yield rate of 844.11â mg h-1 g-1, alongside a corresponding Faradaic efficiency of 33.90 % at -0.4â V vs. reversible hydrogen electrode (RHE). By combining in situ spectroscopic techniques with density functional theory calculations, we demonstrate that efficient C-N coupling is attributed to a tandem system in which the *NH2 and *CO intermediates produced by the Mo and Co active sites of Mo-PCN-222(Co) stabilize the formation of the *CONH2 intermediate. This study provides an effective avenue for the design and synthesis of tandem catalysts for electrocatalytic urea synthesis.
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Hybrid metal halides (HMHs) are a class of materials that combine extraordinary photophysical properties and excellent processability. Their chemical variability allows for the solid-liquid transition toward melt-processable HMHs. Herein, we report the design and synthesis of zero-dimensional HMHs [M(DMSO)6][SbCl6], where the isolated octahedra of [M(DMSO)6]3+ and [SbCl6]3- are alternatively aligned in the crystal structure. The luminescent center of [SbCl6]3- enables the photogeneration of self-trapped excitons, resulting in broadband photoluminescence with a large Stokes shift and a nearly 100% quantum yield. Meanwhile, the release of DMSO ligands from [M(DMSO)6]3+ is controlled by the M-O coordination and thus a low melting point of â¼90 °C is achieved for HMHs. Interestingly, the glass phase is obtained by melt quenching, with a sharp change in photoluminescence colors compared to the crystal phase of melt-processable HMHs. The robust crystal-liquid-glass transition opens a new avenue to tailoring structural disorder and optoelectronic performance in organic-inorganic materials.
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Probiotics have gained significant attention owing to their roles in regulating human health. Recently, spray drying has been considered as a promising technique to produce probiotic powders due to its advantages of high efficiency, cost-saving, and good powder properties. However, the severe environmental conditions from drying and digestion can significantly reduce cell viability, resulting in poor bioaccessibility and bioavailability of live cells. Therefore, there is a need to develop effective targeted delivery systems using spray drying to protect bacteria and to maintain their physiological functions in the targeted sites. This review highlights recent studies about spray-dried targeted delivery vehicles for probiotics, focusing on key strategies to protect bacteria when encountering external stresses, the formation mechanism of particles, the targeted release and colonization mechanisms of live cells in particles with different structures. Advances in the targeted delivery of live probiotics via spray-dried vehicles are still in their early stages. To increase the possibilities for industrialization and commercialization, functional improvement of microcapsules in terms of protection, targeted release, and colonization of bacteria, as well as the effect of spray drying on bacterial physiological functions in the host, need to be further investigated.
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The abnormal accumulation of amyloid ß protein (Aß) is one of the most important causes of Alzheimer's disease (AD) and is usually a detecting biomarker. Curcumin and its derivatives have potential Aß aggregate targeting ability; we synthesized a series of curcumin-based near-infrared fluorescence probes in this study. By characterizing the excitation wavelength and emission wavelength, the imaging characteristics of the investigation in the near-infrared light region were determined; with an increase in the concentration of the probe compounds, the fluorescence intensity showed an upward trend, demonstrating ideal optical characteristics. In vivo, imaging results showed that the synthesized probe compounds could penetrate the blood-brain barrier (BBB) and specifically bind to Aß in the brain of APP/PS1 mice. Especially for compound 3b, the maximum emission wavelength was around 667â¯nm, and the fluorescence signal intensity in the brain of the APP/PS1 mice model was more than twice that of the wild control group at 120â¯min after administration, which could display Aß pathological changes. The fluorescent probes designed in this study can become an effective tool for early AD diagnosis and visual detection.
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Enfermedad de Alzheimer , Curcumina , Ratones , Animales , Péptidos beta-Amiloides/metabolismo , Enfermedad de Alzheimer/patología , Colorantes Fluorescentes/química , Curcumina/química , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Placa Amiloide/diagnóstico , Placa Amiloide/patología , Ratones TransgénicosRESUMEN
KEY MESSAGE: Editing ZmGA20ox3 can achieve the effect similar to applying Cycocel, which can reduce maize plant height and enhance stress resistance. Drought stress, a major plant abiotic stress, is capable of suppressing crop yield performance severely. However, the trade-off between crop drought tolerance and yield performance turns out to be significantly challenging in drought-resistant crop breeding. Several phytohormones [e.g., gibberellin (GA)] have been reported to play a certain role in plant drought response, which also take on critical significance in plant growth and development. In this study, the loss-of-function mutations of GA biosynthesis enzyme ZmGA20ox3 were produced using the CRISPR-Cas9 system in maize. As indicated by the result of 2-year field trials, the above-mentioned mutants displayed semi-dwarfing phenotype with the decrease of GA1, and almost no yield loss was generated compared with wild-type (WT) plants. Interestingly, as revealed by the transcriptome analysis, differential expressed genes (DEGs) were notably enriched in abiotic stress progresses, and biochemical tests indicated the significantly increased ABA, JA, and DIMBOA levels in mutants, suggesting that ZmGA20ox3 may take on vital significance in stress response in maize. The in-depth analysis suggested that the loss function of ZmGA20ox3 can enhance drought tolerance in maize seedling, reduce Anthesis-Silking Interval (ASI) delay while decreasing the yield loss significantly in the field under drought conditions. The results of this study supported that regulating ZmGA20ox3 can improve plant height while enhancing drought resistance in maize, thus serving as a novel method for drought-resistant genetic improvement in maize.