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BACKGROUND: Skin fibrosis affects the normal function of the skin. TGF-ß1 is a key cytokine that affects organ fibrosis. The latency-associated peptide (LAP) is essential for TGF-ß1 activation. We previously constructed and prepared truncated LAP (tLAP), and confirmed that tLAP inhibited liver fibrosis by affecting TGF-ß1. SPACE peptide has both transdermal and transmembrane functions. SPACE promotes the delivery of macromolecules through the stratum corneum into the dermis. This study aimed to alleviate skin fibrosis through the delivery of tLAP by SPACE. METHODS: The SPACE-tLAP (SE-tLAP) recombinant plasmid was constructed. SE-tLAP was purified by nickel affinity chromatography. The effects of SE-tLAP on the proliferation, migration, and expression of fibrosis-related and inflammatory factors were evaluated in TGF-ß1-induced NIH-3T3 cells. F127-SE-tLAP hydrogel was constructed by using F127 as a carrier to load SE-tLAP polypeptide. The degradation, drug release, and biocompatibility of F127-SE-tLAP were evaluated. Bleomycin was used to induce skin fibrosis in mice. HE, Masson, and immunohistochemistry were used to observe the skin histological characteristics. RESULTS: SE-tLAP inhibited the proliferation, migration, and expression of fibrosis-related and inflammatory factors in NIH-3T3 cells. F127-SE-tLAP significantly reduced ECM production, collagen deposition, and fibrotic pathological changes, thereby alleviating skin fibrosis. CONCLUSION: F127-SE-tLAP could increase the transdermal delivery of LAP, reduce the production and deposition of ECM, inhibit the formation of dermal collagen fibers, and alleviate the progression of skin fibrosis. It may provide a new idea for the therapy of skin fibrosis.
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Polietilenos , Polipropilenos , Enfermedades de la Piel , Factor de Crecimiento Transformador beta , Animales , Ratones , Bleomicina/efectos adversos , Colágeno/metabolismo , Fibrosis/tratamiento farmacológico , Hidrogeles/química , Hidrogeles/farmacología , Polietilenos/farmacología , Polipropilenos/farmacología , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Enfermedades de la Piel/inducido químicamente , Enfermedades de la Piel/tratamiento farmacológico , Enfermedades de la Piel/metabolismo , Proteínas Smad/efectos de los fármacos , Proteínas Smad/metabolismo , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patologíaRESUMEN
Coxsackievirus A16 (CV-A16) is a significant etiologic agent of hand, foot, and mouth disease (HFMD) and herpangina (HA), with the capacity to progress to severe complications, including encephalitis, aseptic meningitis, acute flaccid paralysis, myocarditis, and other critical conditions. Beijing's epidemiological surveillance system, established in 2008, encompasses 29 hospitals and 16 district disease control centers. From 2019 to 2021, the circulation of CV-A16 was characterized by the co-circulation of B1a and B1b clades. Multiple cases of HFMD linked to clade B1c has not been reported in Beijing until 2022. This study enrolled 400 HFMD and 493 HA cases. Employing real-time RT-PCR, 368 enterovirus-positive cases were identified, with 180 selected for sequencing. CV-A16 was detected in 18.89% (34/180) of the cases, second only to CV-A6, identified in 63.33% (114/180). Full-length VP1 gene sequences were successfully amplified and sequenced in 22 cases, revealing the presence of clades B1a, B1b, and B1c in 14, 3, and 5 cases, respectively. A cluster of five B1c clade cases occurred between June 29 and July 17, 2022, within a 7-km diameter region in Shunyi District. Phylogenetic analysis of five complete VP1 gene sequences and two full-genome sequences revealed close clustering with the 2018 Indian strain (GenBank accession: MH780757.1) within the B1c India branch, with NCBI BLAST results showing over 98% similarity. Comparative sequence analysis identified three unique amino acid variations (P3S, V25A, and I235V). The 2022 Shunyi District HFMD cases represent the first instances of spatiotemporally correlated CV-A16 B1c clade infections in Beijing, underscoring the necessity for heightened surveillance of B1c clade CV-A16 in HFMD and HA in this region.
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Enfermedad de Boca, Mano y Pie , Filogenia , Humanos , Beijing/epidemiología , Enfermedad de Boca, Mano y Pie/virología , Enfermedad de Boca, Mano y Pie/epidemiología , Masculino , Femenino , Preescolar , Lactante , Niño , Genotipo , Enterovirus/genética , Enterovirus/clasificación , Enterovirus/aislamiento & purificación , Proteínas de la Cápside/genética , Adolescente , Monitoreo EpidemiológicoRESUMEN
Animal studies indicate that bisphenol A (BPA) has obesogenic effects. Recent experiments reported similar endocrine-disrupting effects of bisphenol F (BPF) and bisphenol S (BPS), which are substitutes of BPA. The aim of this study was to investigate the exposure levels of these bisphenols in pregnant women and their effects on the physical development of infants aged 0-12 months. This study recruited pregnant women who gave birth at a hospital between February 2019 and September 2020. Urine samples from these pregnant women in the third trimester of pregnancy were detected by using ultrahigh-performance liquid chromatography-triple quadruple mass spectrometry. Follow-ups at 6 and 12 months of age were conducted by telephone by pediatricians using a structured questionnaire. Multiple linear regressions were used to determine the associations between bisphenol concentrations and infant weight. A total of 113 mother-child pairs had complete questionnaires and urine samples as well as data on newborns aged 6 months and 12 months. The detection rates of urinary BPA, BPF, and BPS in pregnant women were 100, 62.83, and 46.02%, respectively. Their median levels are 5.84, 0.54, and 0.07 µg/L, respectively. Increased urinary BPA and BPF concentrations during pregnancy were significantly associated with lower birth weight (standardized regression coefficients [ß] = -0.081 kg, 95% confidence interval [CI]: -0.134 to -0.027; ß = -0.049 kg, 95% CI: -0.097 to -0.001). In addition, urinary BPA and BPF concentrations during pregnancy were positively associated with weight growth rate from 0 to 6 months (ß = 0.035 kg/mouth, 95% CI: 0.00-0.064; ß = 0.028 kg/mouth, 95% CI: 0.006-0.050), especially in female infants (ß = 0.054 kg/mouth, 95% CI: 0.015-0.093; ß = 0.035 kg/mouth, 95% CI: 0.005-0.065). Therefore, maternal BPA and BPF levels during pregnancy were negatively correlated with birth weight and positively correlated with the growth rate of infant weight at 0-6 months of age, especially in female infants.
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Compuestos de Bencidrilo , Fenoles , Sulfonas , Humanos , Femenino , Fenoles/orina , Embarazo , Compuestos de Bencidrilo/orina , China , Adulto , Sulfonas/orina , Recién Nacido , Peso al Nacer/efectos de los fármacos , Lactante , Recién Nacido de Bajo Peso , Exposición Materna/efectos adversos , MasculinoRESUMEN
The residual polarization of antiferroelectric ceramics is very small, yet they possess high energy storage density and efficiency. Incorporating antiferroelectric ceramic particles into a polymer matrix is beneficial for improving the energy storage performance of composites. However, excessive amounts of ceramic particles can lead to aggregation within the polymer, resulting in defects and a significant reduction in composite film performance. In this study, the antiferroelectric AgNbO3 is selected as the filler and modified with silane coupling agent KH550. poly(vinylidene fluoride) (PVDF) and polymethyl methacrylate (PMMA) are blended as the matrix, and the energy storage performance of the composite is improved by adjusting the additional amount of PVDF. The structure, dielectric properties, and energy storage properties of the composites are systematically studied. The results show that hydrogen bonds are formed between PVDF and PMMA, and PVDF and PMMA are tightly bonded under the action of hydrogen bonds. The compatibility of PVDF with PMMA is optimal when the mass fraction of PVDF is 30 wt%. Moreover, with the synergistic effect of the antiferroelectric filler AgNbO3 , the breakdown strength of AgNbO3 /PVDF/PMMA composites reaches 430 kV mm-1 , and the energy storage density reaches 14.35 J cm-3 .
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Polímeros de Fluorocarbono , Polímeros , Polimetil Metacrilato , Polivinilos , CerámicaRESUMEN
In this work, a sensitive signal-on electrochemiluminescence biosensor using liposome-encapsuled 1,1,2,2-tetra(4-carboxylphenyl)ethylene (TPE) as a promising aggregation-induced electrochemiluminescence (AIECL) emitter for detection of biomarkers was developed. Aggregation-induced enhancement occurs internally through the spatial confinement effect and intramolecular self-encapsulation of encapsulating TPE and triethylamine (TEA) molecules in liposome cavities. Peptide sequence WTGWCLNPEESTWGFCTGSF (WF-20) was used to replace the antibody for reducing the steric hindrance of the sensing surface while taking into account the affinity. The proposed sensing strategies showed satisfactory properties for detection of human epidermal growth factor receptor 2 (HER2) ranging from 0.01 to 500 ng/mL with a limit of detection of 6.65 pg/mL. The results confirmed that encapsulation of luminescent molecules in the vesicle structure for triggering the AIECL phenomenon is a promising method to prepare a signal label for a trace detection biomarker.
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Técnicas Biosensibles , Estilbenos , Humanos , Liposomas , Receptor ErbB-2 , Estilbenos/química , Técnicas Biosensibles/métodos , Mediciones Luminiscentes/métodos , Técnicas Electroquímicas/métodos , Límite de DetecciónRESUMEN
To ensure drinking water quality, the development of rapid and accurate analytical methods is essential. Herein, a highly sensitive electrochemiluminescence (ECL) aptasensor-based on the signal on-off-on strategy was developed to detect the water pollutant microcystin-LR (MC-LR). This strategy was based on a newly prepared ruthenium-copper metal-organic framework (RuCu MOF) as the ECL signal-transmitting probe and three types of PdPt alloy core-shell nanocrystals with different crystal structures as signal-off probes. Compounding the copper-based MOF (Cu-MOF) precursor with ruthenium bipyridyl at room temperature facilitated the retention of the intrinsic crystallinity and high porosity of the MOFs as well as afforded excellent ECL performance. Since bipyridine ruthenium in RuCu MOFs could transfer energies to the organic ligand (H3BTC), the ultra-efficient ligand luminescent ECL signal probe was finally obtained, which greatly improved the sensitivity of the aptasensor. To further improve the sensitivity of the aptasensor, the quenching effects of noble metal nanoalloy particles with different crystal states were investigated, which contained PdPt octahedral (PdPtOct), PdPt rhombic dodecahedral (PdPtRD), and PdPt nanocube (PdPtNC). Among them, the PdPtRD nanocrystal exhibited higher activity and excellent durability, stemming from the charge redistribution caused by the hybridization of Pt and Pd atoms. Moreover, PdPtRD could also load more -NH2-DNA strands because it exposed more active sites with a large specific surface area. The fabricated aptasensor exhibited outstanding sensitivity and stability in MC-LR detection, with a linear detection range of 0.0001-50 ng mL-1. This study provides valuable directions for the application of alloy nanoparticles of noble metals and bimetallic MOFs in the field of ECL immunoassay.
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Técnicas Biosensibles , Nanopartículas del Metal , Estructuras Metalorgánicas , Rutenio , Estructuras Metalorgánicas/química , Cobre/química , Rutenio/química , Ligandos , Mediciones Luminiscentes/métodos , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Aleaciones , Nanopartículas del Metal/química , Límite de DetecciónRESUMEN
Catalysts can effectively accelerate the reaction kinetics process and are recognized as the core to realize the conversion and supply of carbon-free energy. However, the active sites of catalysts, especially nanocatalysts, usually undergo dynamic structural evolution under realistic working conditions, which may be induced by various reaction effects such as the applied voltages, electrolytes, or adsorbed intermediates. Therefore, in-depth and systemic insights into the nature of the active sites involved under the working conditions are prerequisites for correlating structure-performance relationships. However, uncovering and identifying active sites under operation conditions are still formidable scientific and technical challenges, which are severely hindered by the complex physical and chemical processes occurring on the active sites. Meanwhile, complementary and important information could be missed by conducting only the conventionally employed ex situ microscopic and spectroscopic measurements. Accordingly, it is highly desirable for us to develop the ever-increasing in situ synchrotron-based techniques to identify the nature of active sites, which renders the rational design of functional catalysts achievable.In this Account, we elaborately highlight the substantial achievements in cutting-edge in situ X-ray spectroscopy (XAS) techniques by presenting several representative carbon-neutral electrocatalytic examples performed in our group to broadcast the principles and virtues of identifying the active sites and tracing intermediate species during electrocatalytic water splitting and electrocatalytic CO2 reduction (ECR). Specifically, we believe that the interactions between the active sites and the support as well as the adsorption behaviors of intermediates are considered to be the important factors that govern the performance in the water splitting reaction. Meanwhile, the structural rearrangement of alloy catalysts driven by the cathodic potential significantly governs the activity and selectivity toward ECR. More importantly, the directions and suggestions for addressing the current limitations and pitfalls that we may encounter in the course of executing in situ experiments are also provided. Accordingly, it is necessary to use multiple in situ synchrotron-based techniques to obtain the comprehensive details. Furthermore, bridging the gap between the real energy devices and half-reactions could help us to approach the realistic mechanism. Beyond that, developing the rapid time resolution of in situ XAS will overcome the challenge of timescale mismatch to capture the faster structural kinetics of catalysts. Therefore, this Account is aimed to increase the awareness and appreciation of conducting in situ investigations on energy conversion reactions, which would be a guideline for us to explore catalytic scopes that remain challenging.
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Dióxido de Carbono , Sincrotrones , Aleaciones , Dominio Catalítico , Análisis Espectral/métodos , Agua/químicaRESUMEN
Although traditional nanomedicines have enhanced the therapeutic efficacy and improved the survival quality of cancer patients, random drug release and drug resistance are deep-rooted problems hindering their clinical application. A precise nanoplatform combing chemotherapy and photodynamic therapy (PDT) is developing as a new therapeutic strategy to overcome the above challenges. Herein, a novel supramolecular nanomedicine is ingeniously constructed for in situ self-boosting cancer photochemotherapy. Hydrophilic polyethylene glycol (PEG) chains or ß-cyclodextrin (ß-CD) hosts are first conjugated onto tetraphenyl porphyrin (TCPP) to improve the solubility of TCPP and decrease their π-π stacking interactions, guaranteeing a high-efficiency PDT. Then, two camptothecin (CPT) molecules are linked together via a reactive oxygen species (ROS)-responsive thioketal bond, which averts the premature burst release of CPT and realizes in situ drug release at the tumor site where PDT is performed, resulting in an enhanced chemotherapy. Benefiting from the collaboration of host-guest complexation between ß-CD and CPT, multiple intermolecular hydrogen bonds of ß-CD, π-π stacking interactions among CPT and TCPP as well as PEG shell protection, a prolonged blood circulation time, and a selective tumor accumulation are acquired, which facilitate the synergistic photochemotherapy and bring a pre-eminent antitumor response with a low systemic toxicity.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Nanomedicina Teranóstica , Fotoquimioterapia/métodos , Neoplasias/tratamiento farmacológico , Nanomedicina , Polietilenglicoles/química , Línea Celular Tumoral , Fármacos Fotosensibilizantes , Nanopartículas/químicaRESUMEN
Organic film capacitors have incredibly high power density and have an irreplaceable position in pulsed power systems, high-voltage power transmission networks and other fields. At present, the energy storage density and energy storage efficiency of organic film capacitors are relatively low, resulting in excessive equipment volume. The performance of organic film capacitors is determined by polymer materials, so it is crucial to develop a polymer composite with high energy storage density and high charge-discharge efficiency. Poly(vinylidene fluoride-co-chlorotrifluoroethylene) (P(VDF-CTFE)) is incorporated into the polyvinylidene fluoride (PVDF) matrix by solution blending. The successful preparation of the all-polymer composite material solves the problems of low breakdown electric field strength, low discharge energy density, and low charge-discharge efficiency of high-dielectric ferroelectric materials. The discharge energy density of the PVDF/P(VDF-CTFE) (70/30) film is more than twice that of pure PVDF due to the increase of phases α and γ and the decrease of crystallinity. Under the breakdown electric field (380 kV mm-1 ), PVDF/P(VDF-CTFE) (70/30) film also has an ultrahigh energy storage efficiency of 64%. The relationship between the structure and properties of composite materials is investigated in this study, which has important implications for the development of capacitors with high energy storage density.
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Electricidad , Polímeros de Fluorocarbono , Polímeros , PolivinilosRESUMEN
An immobilized metal affinity (IMAC) adsorbent was prepared for selective enrichment of adenine type CKs, via grafting polymer chain pendant with iminodiacetic acid (IDA) from polydopamine (PDA)/polyethyleneimine (PEI)-coated magnetic graphene oxide (magGO) via surface-initiated-atom transfer radical polymerization (SI-ATRP). The prepared IMAC sorbent exhibited remarkable adsorption performances and good selectivity for adenine-type CKs and was utilized as a sorbent of magnetic solid-phase extraction (MSPE) for effective enrichment of four adenine-type CKs in bean sprouts. Under the optimized extraction conditions, an analytical method for four adenine type CKs in bean sprouts was established by combining the MSPE combined with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The recoveries of the analytes were between 80.4 ± 1.9% and 114.6 ± 1.5% (n = 3). The limits of detection (LODs) range from 0.63 to 2.30 pgâ mL-1. The relative standard deviations of intra-day and inter-day were less than 12.6%. The established method was successfully applied to the selective extraction and sensitive detection of trace adenine-type CKs in plant samples.
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Citocininas , Polietileneimina , Citocininas/análisis , Citocininas/química , Polietileneimina/química , Espectrometría de Masas en Tándem/métodos , Plantas , Polímeros/química , Fenómenos MagnéticosRESUMEN
Pepper is renowned worldwide for its distinctive spicy flavor. While the gene expression characteristics of the capsaicinoid biosynthesis pathway have been extensively studied, there are already a few reports regarding transcriptional regulation in capsaicin biosynthesis. In this study, 73 WRKYs were identified in the genome of Capsicum chinense, and their physicochemical traits, DNA, and protein sequence characteristics were found to be complex. Combining RNA-seq and qRT-PCR data, the WRKY transcription factor CA06g13580, which was associated with the accumulation tendency of capsaicinoid, was screened and named CcWRKY25. CcWRKY25 was highly expressed in the placenta of spicy peppers. The heterologous expression of CcWRKY25 in Arabidopsis promoted the expression of genes PAL, 4CL1, 4CL2, 4CL3, CCR, and CCoAOMT and led to the accumulation of lignin and flavonoids. Furthermore, the expression of the capsaicinoid biosynthesis pathway genes (CBGs) pAMT, AT3, and KAS was significantly reduced in CcWRKY25-silenced pepper plants, resulting in a decrease in the amount of capsaicin. However, there was no noticeable difference in lignin accumulation. The findings suggested that CcWRKY25 could be involved in regulating capsaicinoid synthesis by promoting the expression of genes upstream of the phenylpropanoid pathway and inhibiting CBGs' expression. Moreover, the results highlighted the role of CcWRKY25 in controlling the pungency of pepper and suggested that the competitive relationship between lignin and capsaicin could also regulate the spiciness of the pepper.
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Capsicum , Capsicum/metabolismo , Capsaicina/metabolismo , Lignina/metabolismo , Factores de Transcripción/metabolismo , Frutas/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
When the total phenolic content (TPC) and antioxidant activity of sea buckthorn juice were assayed by spectrophotometry, the reaction solutions were not clarified, so centrifugation or membrane treatment was needed before determination. In order to find a suitable method for determining TPC and antioxidant activity, the effects of centrifugation and nylon membrane treatment on the determination of TPC and antioxidant activity in sea buckthorn juice were studied. TPC was determined by the Folin-Ciocalteau method, and antioxidant activity was determined by DPPH, ABTS, and FRAP assays. For Treatment Method (C): the sample was centrifuged for 10 min at 10,000 rpm and the supernatant was taken for analysis. Method (CF): The sample was centrifuged for 10 min at 4000 rpm, filtered by Nylon 66 filtration membranes with pore size of 0.22 µm, and taken for analysis. Method (F): the sample was filtered by Nylon 66 filtration membranes with pore size of 0.22 µm and taken for analysis. Method (N): after the sample of ultrasonic extract solution reacted completely with the assay system, the reaction solution was filtered by Nylon 66 filtration membranes with pore size of 0.22 µm and colorimetric determination was performed. The results showed that centrifugation or transmembrane treatment could affect the determination of TPC and antioxidant activity of sea buckthorn juice. There was no significant difference (p > 0.05) between methods (CF) and (F), while there was a significant difference (p < 0.05) between methods (C) (F) (N) or (C) (CF) (N). The TPC and antioxidant activity of sea buckthorn juice determined by the four treatment methods showed the same trend with fermentation time, and the TPC and antioxidant activity showed a significant positive correlation (p < 0.05). The highest TPC or antioxidant activity measured by method (N) indicates that method (N) has the least loss of TPC or antioxidant activity, and it is recommended for sample assays.
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Antioxidantes , Hippophae , Antioxidantes/farmacología , Antioxidantes/análisis , Polifenoles/farmacología , Polifenoles/análisis , Hippophae/química , Nylons , Fenoles/análisis , Frutas/química , CentrifugaciónRESUMEN
The wide application of pepper is mostly related to the content of capsaicin, and phenylpropanoid metabolism and its branch pathways may play an important role in the biosynthesis of capsaicin. The expression level of MYB24, a transcription factor screened from the transcriptome data of the pepper fruit development stage, was closely related to the spicy taste. In this experiment, CcMYB24 was cloned from Hainan Huangdenglong pepper, a hot aromatic pepper variety popular in the world for processing, and its function was confirmed by tissue expression characteristics, heterologous transformation in Arabidopsis thaliana, and VIGS technology. The results showed that the relative expression level of CcMYB24 was stable in the early stage of pepper fruit development, and increased significantly from 30 to 50 days after flowering. Heterologous expression led to a significant increase in the expression of CcMYB24 and decrease in lignin content in transgenic Arabidopsis thaliana plants. CcMYB24 silencing led to a significant increase in the expression of phenylpropanoid metabolism pathway genes PAL, 4CL, and pAMT; lignin branch CCR1 and CAD; and capsaicin pathway CS, AT3, and COMT genes in the placenta of pepper, with capsaicin content increased by more than 31.72% and lignin content increased by 20.78%. However, the expression of PAL, pAMT, AT3, COMT, etc., in the corresponding pericarps did not change significantly. Although CS, CCR1, and CAD increased significantly, the relative expression amount was smaller than that in placental tissue, and the lignin content did not change significantly. As indicated above, CcMYB24 may negatively regulate the formation of capsaicin and lignin by regulating the expression of genes from phenylpropanoid metabolism and its branch pathways.
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Proteínas de Arabidopsis , Arabidopsis , Capsicum , Embarazo , Femenino , Humanos , Capsicum/metabolismo , Capsaicina/metabolismo , Lignina/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Placenta/metabolismo , Frutas/química , Regulación de la Expresión Génica de las Plantas , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas de Arabidopsis/metabolismoRESUMEN
A series of mono- and bis-polyethylene glycol (PEG)-substituted BF2-azadipyrromethene fluorophores have been synthesized with emissions in the near-infrared region (700-800 nm) for the purpose of fluorescence guided intraoperative imaging; chiefly ureter imaging. The Bis-PEGylation of fluorophores resulted in higher aqueous fluorescence quantum yields, with PEG chain lengths of 2.9 to 4.6 kDa being optimal. Fluorescence ureter identification was possible in a rodent model with the preference for renal excretion notable through comparative fluorescence intensities from the ureters, kidneys and liver. Ureteral identification was also successfully performed in a larger animal porcine model under abdominal surgical conditions. Three tested doses of 0.5, 0.25 and 0.1 mg/kg all successfully identified fluorescent ureters within 20 min of administration which was sustained up to 120 min. 3-D emission heat map imaging allowed the spatial and temporal changes in intensity due to the distinctive peristaltic waves of urine being transferred from the kidneys to the bladder to be identified. As the emission of these fluorophores could be spectrally distinguished from the clinically-used perfusion dye indocyanine green, it is envisaged that their combined use could be a step towards intraoperative colour coding of different tissues.
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Espectroscopía Infrarroja Corta , Uréter , Porcinos , Animales , Espectroscopía Infrarroja Corta/métodos , Colorantes Fluorescentes/química , Riñón , Vejiga Urinaria , Polietilenglicoles/química , Imagen Óptica/métodosRESUMEN
Mandibuloacral dysplasia (MAD) is a rare autosomal recessive disorder, mainly caused by pathogenic variants of the LMNA and ZMPSTE24 genes. In this study, we reported the first case of a patient with type B cranial and mandibular dysplasia in China. The patient presented with distinctive facial features, feeding difficulties, significant physical retardation, and overall developmental delay with abnormal tooth and bone development. Trio-whole exome sequencing analysis showed that the patient carried compound heterozygous mutations of c.743C>T (p.Pro248Leu) (dbSNP: rs121908095) and the loss of exons 1-10 of the ZMPSTE24 gene. Sanger sequencing and real-time quantitative PCR (RT-qPCR) showed that these two mutations were inherited from the patient's phenotypically normal mother and father, respectively. By summarizing and analyzing the characteristics of this case and the pedigree of the family, we suggested that trio-whole-exome sequencing could be performed to assist in the diagnosis of diseases that are difficult to be diagnosed definitively based on clinical phenotypes. The publication of this case has improved clinicians' understanding of MAD disease and provide new clinical information for the subsequent genetic study of this disease.
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Lipodistrofia , Metaloendopeptidasas , Humanos , Metaloendopeptidasas/genética , Lamina Tipo A/genética , Mutación , Lipodistrofia/genética , Fenotipo , Proteínas de la Membrana/genéticaRESUMEN
BACKGROUNDS: Surgical resection and adjunct chemotherapy or radio-therapy has been applied for the therapy of superficial malignant tumor in clinics. Whereas, there are still some problems limit its clinical use, such as severe pains and side effect. Thus, it is urgent need to develop effective, minimally invasive and low toxicity therapy stagey for superficial malignant tumor. Topical drug administration such as microneedle patches shows the advantages of reduced systemic toxicity and nimble application and, as a result, a great potential to treat superficial tumors. METHODS: In this study, microneedle (MN) patches were fabricated to deliver photosensitizer IR820 and chemotherapy agent cisplatin (CDDP) for synergistic chemo-photodynamic therapy against breast cancer. RESULTS: The MN could be completely inserted into the skin and the compounds carrying tips could be embedded within the target issue for locoregional cancer treatment. The photodynamic therapeutic effects can be precisely controlled and switched on and off on demand simply by adjusting laser. The used base material vinylpyrrolidone-vinyl acetate copolymer (PVPVA) is soluble in both ethanol and water, facilitating the load of both water-soluble and water-insoluble drugs. CONCLUSIONS: Thus, the developed MN patch offers an effective, user-friendly, controllable and low-toxicity option for patients requiring long-term and repeated cancer treatments.
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Neoplasias de la Mama/tratamiento farmacológico , Cisplatino/farmacología , Sistemas de Liberación de Medicamentos/métodos , Verde de Indocianina/farmacología , Fotoquimioterapia/métodos , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Liberación de Fármacos , Quimioterapia , Femenino , Humanos , Verde de Indocianina/análogos & derivados , Ratones Endogámicos BALB C , Fármacos Fotosensibilizantes/administración & dosificación , Povidona/análogos & derivadosRESUMEN
An immobilized metal affinity (IMA) adsorbent was prepared by grafting bottlebrush polymer pendant with iminodiacetic acid (IDA) from the surface of polydopamine (PDA)-coated magnetic graphene oxide (magGO), via surface-initiated atom transfer radical polymerization (SI-ATRP). Poly(hydroxyethyl methacrylate) (PHEMA) was grafted firstly from the PDA-coated magGO as the backbone, and then poly(glycidyl methacrylate) was grafted from the PHEMA chains via the second SI-ATRP to afford the bottlebrush polymer-grafted magGO Thereafter, IDA was anchored on the nanocomposites to produce the IMA adsorbent after chelating copper ions. The adsorbent was characterized by various physical and physicochemical methods. Its adsorption properties were evaluated by using histidine-rich proteins (bovine hemoglobin, BHb) and other proteins (lysozyme and cytochrome-C). The results show that its maximum adsorption capacity to BHb was 378.6 mg g-1, and the adsorption equilibrium can be quickly reached within 1 h. The adsorbent has excellent reproducibility and reusability. It has been applied to selectively purify hemoglobin from human whole blood, indicating its potential in practical applications. Graphical abstract.
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Grafito/química , Hemoglobinas/aislamiento & purificación , Adsorción , Animales , Bovinos , Cobre/química , Humanos , Iminoácidos/química , Indoles/química , Extracción Líquido-Líquido/métodos , Fenómenos Magnéticos , Polihidroxietil Metacrilato/química , Polímeros/química , Ácidos Polimetacrílicos/química , Reproducibilidad de los ResultadosRESUMEN
For polymer-based controlled release drug products (e.g. microspheres and implants), active pharmaceutical ingredient distribution and microporosity inside the polymer matrix are critical for product performance, particularly drug release kinetics. Due to the decreasing domain size and increasing complexity of such products, conventional characterization and release test techniques are limited by their resolution and speed. In this study, samples of controlled release poly(lactic-co-glycolic acid) microspheres in the diameter range of 30-80 µm are investigated with focused ion beam scanning electron microscope imaging at 20 nm or higher resolution. Image data is quantified with artificial intelligence-based image analytics to provide size distributions of drug particles and pores within the microsphere sample. With an innovative image-based numerical simulation method, release profiles are predicted in a matter of days regardless of the designed release time. A mechanistic understanding on the impact of porosity to the interplays of drug, formulation, process, and dissolution was gained.
Asunto(s)
Preparaciones de Acción Retardada , Microscopía Electrónica de Rastreo/métodos , Microesferas , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/administración & dosificación , Inteligencia Artificial , Composición de Medicamentos , Cinética , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Porosidad , SolubilidadRESUMEN
A sandwich-type electrochemiluminescence (ECL) immunosensor for the N-terminal brain natriuretic peptide (NT-proBNP) is described. The assay is based on the quenching of the ECL of graphite-like carbon nitride (g-C3N4) by polydopamine (PDA). Two-dimensional g-C3N4 is grown in-situ on titanium dioxide nanoflowers (TiO2 NFs). The macroporous structure of the NFs enhances the interfacial stability of g-C3N4, and also promotes the ECL reaction of g-C3N4 with the co-reactant. The introduction of gold nanoparticles into the matrix further enhances the ECL and facilitates the immobilization of capture antibodies. The nanoquencher used to label the secondary antibody is synthesized by catalytic polymerization of dopamine in the presence of bimetallic NiPd nanoparticles. The nanoquencher preserves the high reactivity of polydopamine and quenches the ECL of the g-C3N4/TiO2 system. Compared to other methods, the detection limit for NT-proBNP is decreased to 50 fgâmL-1. Graphical abstract Schematic presentation of the electrochemiluminescence (ECL) process of the immunosensor: titanium dioxide nanoflowers@graphite-like carbon nitride-gold nanoparticles (TiO2 NFs@g-C3N4-Au) as luminophor, and polydopamine (PDA) as nanoquencher.
Asunto(s)
Técnicas Biosensibles/métodos , Inmunoensayo/métodos , Indoles/química , Péptido Natriurético Encefálico/análisis , Fragmentos de Péptidos/análisis , Polímeros/química , Catálisis , Electroquímica , Mediciones Luminiscentes , Péptido Natriurético Encefálico/química , Fragmentos de Péptidos/química , Polimerizacion , Temperatura , Titanio/químicaRESUMEN
Plastic particles are widely present in the natural environment and are highly likely to interact with bacteria (the ubiquitous microbes in the natural environment), which might affect the transport and deposition of bacteria in porous media. In this study, the significance of plastic particles from nanoscale to micrometer-scale (0.02-2 µm) on the transport and deposition behaviors of bacteria ( Escherichia coli) in quartz sand was examined under environmentally relevant conditions in both NaCl and CaCl2 solutions at pH 6. The results showed that the presence of different-sized plastic particles did not affect bacterial transport behaviors at low ionic strength (10 mM NaCl and 1 mM CaCl2), whereas, at high ionic strength conditions (50 mM NaCl and 5 mM in CaCl2), plastic particles increased bacterial transport in quartz sand. At low ionic strength conditions, the mobility of both plastic particles and bacteria was high, which might drive the negligible effects of plastic particles on bacterial transport behaviors. The mechanisms driving the enhanced cell transport at high ionic strength were different for different-sized plastic particles. Specifically, for 0.02 µm nanoplastic particles, the adsorption of plastic particles onto cell surfaces and the repel effect induced by suspended plastic particles contributed to the increased cell transport. As for 0.2 µm microplastics (MPs), the suspended plastic particles induced repel effect contributed to the increased cell transport, whereas, for 2 µm MPs, the competition deposition sites by the plastic particles were the contributor to the increased cell transport.