RESUMEN
Micro(nano)plastic, as a new type of environmental pollutant, have become a potential threat to the life and health of various stages of biology. However, it is not yet clear whether they will affect brain development in the fetal stage. Therefore, this study aims to explore the potential effects of nanoplastics on the development of fetal rat brains. To assess the allocation of NPs (25â¯nm and 50â¯nm) in various regions of the fetal brain, pregnant rats were exposed to concentrations (50, 10, 2.5, and 0.5â¯mg/kg) of PS-NPs. Our results provided evidence of the transplacental transfer of PS-NPs to the fetal brain, with a prominent presence observed in several cerebral regions, notably the cerebellum, hippocampus, striatum, and prefrontal cortex. This distribution bias might be linked to the developmental sequence of each brain region. Additionally, we explored the influence of prenatal exposure on the myelin development of the cerebellum, given its the highest PS-NP accumulation in offspring. Compared with control rats, PS-NPs exposure caused a significant reduction in myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) expression, a decrease in myelin thickness, an increase in cell apoptosis, and a decline in the oligodendrocyte population. These effects gave rise to motor deficits. In conclusion, our results identified the specific distribution of NPs in the fetal brain following prenatal exposure and revealed that prenatal exposure to PS-NPs can suppress myelin formation in the cerebellum of the fetus.
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Encéfalo , Vaina de Mielina , Poliestirenos , Animales , Femenino , Embarazo , Encéfalo/efectos de los fármacos , Encéfalo/embriología , Encéfalo/metabolismo , Vaina de Mielina/efectos de los fármacos , Vaina de Mielina/metabolismo , Ratas , Poliestirenos/toxicidad , Contaminantes Ambientales/toxicidad , Proteína Básica de Mielina/metabolismo , Exposición Materna , Nanopartículas/toxicidad , Apoptosis/efectos de los fármacos , Microplásticos/toxicidad , Ratas Sprague-Dawley , Intercambio Materno-Fetal , Feto/efectos de los fármacosRESUMEN
Triple-negative breast cancer (TNBC) is the most lethal subtypes of breast cancer. Although chemotherapy is considered the most effective strategy for TNBC, most chemotherapeutics in current use are cytotoxic, meaning they target antiproliferative activity but do not inhibit tumor cell metastasis. Here, a TNBC-specific targeted liposomal formulation of epalrestat (EPS) and doxorubicin (DOX) with synergistic effects on both tumor cell proliferation and metastasis is described. These liposomes are biocompatible and effectively target tumor cells owing to hyaluronic acid (HA) modification on their surface. This active targeting, mediated by CD44-HA interaction, allows DOX and EPS to be delivered simultaneously to tumor cells in vivo, where they suppress not only TNBC tumor growth and the epithelial-mesenchymal transition, but also cancer stem cells, which collectively suppress tumor growth and metastasis of TNBC and may also act to prevent relapse of TNBC.
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Neoplasias de la Mama Triple Negativas , Línea Celular Tumoral , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Humanos , Ácido Hialurónico , Liposomas , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
The airliner cabin environment is very important to the health of passengers and crew members, and the use of high-efficiency particulate air (HEPA) filters for recirculated air in the environmental control systems (ECS) is essential for the removal of airborne particles such as SARS CoV-2 aerosols. A HEPA filter should be high efficiency, low-pressure drop, high dust-holding capacity (DHC), lightweight, and strong for use in aircraft. We conducted an experimental study on 23 HEPA filters with glass fiber media that are used in different commercial airliner models. The tested filters had a median filtration efficiency of >99.97% for particles with a diameter of 0.3-0.5 µm, a pressure drop of 134-412 Pa at rated airflow rate, and a DHC of 32.2-37.0 g/m2 . The use of nanofiber media instead of glass fiber media can reduce the pressure drop by 66.4%-94.3% and significantly increase the quality factor by analysis of literature data. The disadvantages of poor fire resistance and small DHC can be overcome by the use of flame-retardant polymers and fiber structural design. As a new lightweight and environmentally friendly filter material, nanofiber media could be used as air filters in ECS in the future.
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Filtros de Aire , Contaminación del Aire Interior , COVID-19 , Aeronaves , COVID-19/prevención & control , Polvo , Filtración , Humanos , Polímeros , Aerosoles y Gotitas RespiratoriasRESUMEN
The separation of plasma from blood cells in whole blood is an essential step for many diagnostic and therapeutic applications. However, the current point-of-care plasma separation approaches have not yet satisfied the need for a rapid, high-flux, and low-cost process. Here, we report a portable, low-cost, disposable membrane-based plasma separation device that enables rapid plasma extraction from whole blood. Rapid separation of plasma can be obtained with a simple three-step operation: blood injection, separation, and plasma collection. Our device benefits from the zwitterionic polyurethane-modified cellulose acetate (PCBU-CA) membrane, which can greatly inhibit the surface fouling of blood cells and membrane flux decline. The zwitterionic coating is stable on the membrane surface during blood filtration and leads to a 60% decrease in surface fibrinogen adsorption than a nonmodified membrane surface. The ultralow-blood-fouling properties of the PCBU-CA membrane enable rapid, continuous separation of plasma: within 10 min, the device can yield 0.5-0.7 mL of plasma from 10 mL of whole blood. The extracted plasma is verified as cell-free, exhibits a low hemoglobin level, and has a high protein recovery. Our PCBU-CA membrane provides a pathway for developing a high-efficiency portable plasma separation device that can reduce the time to diagnosis, allow effective patient care, and eventually reduce hospital costs.
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Membranas Artificiales , Poliuretanos , Adsorción , Fibrinógeno , Humanos , PlasmaRESUMEN
Butenolide derivatives have the potential to be effective and environmentally friendly antifouling agents. In the present study, a butenolide derivative was structurally modified into Boc-butenolide to increase its melting point and remove its foul smell. The structurally modified Boc-butenolide demonstrated similar antifouling capabilities to butenolide in larval settlement bioassays but with significantly lower toxicity at high concentrations. Release-rate measurements demonstrated that the antifouling compound Boc-butenolide could be released from polycaprolactone-polyurethane (PCL-PU)-based coatings to inhibit the attachment of foulers. The coating matrix was easily degraded in the marine environment. The performance of the Boc-butenolide antifouling coatings was further examined through a marine field test. The coverage of biofouler on the Boc-butenolide coatings was low after 2 months, indicating the antifouling potential of Boc-butenolide.
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4-Butirolactona/análogos & derivados , Incrustaciones Biológicas/prevención & control , Carbamatos/farmacología , Poliésteres/farmacología , Poliuretanos/farmacología , 4-Butirolactona/química , 4-Butirolactona/farmacología , Animales , Carbamatos/química , Larva , Pintura , Poliquetos , Poliésteres/química , Poliuretanos/química , ThoracicaRESUMEN
Fluorine is widely dispersed in nature and has multiple physiological functions. Although it is usually regarded as an essential trace element for humans, this view is not held universally. Moreover, chronic fluorosis, mainly characterized by skeletal fluorosis, can be induced by long-term excessive fluoride consumption. High concentrations of fluoride in the environment and drinking water are major causes, and patients with skeletal fluorosis mainly present with symptoms of osteosclerosis, osteochondrosis, osteoporosis, and degenerative changes in joint cartilage. Etiologies for skeletal fluorosis have been established, but the specific pathogenesis is inconclusive. Currently, active osteogenesis and accelerated bone turnover are considered critical processes in the progression of skeletal fluorosis. In recent years, researchers have conducted extensive studies in fields of signaling pathways (Wnt/ß-catenin, Notch, PI3K/Akt/mTOR, Hedgehog, parathyroid hormone, and insulin signaling pathways), stress pathways (oxidative stress and endoplasmic reticulum stress pathways), epigenetics (DNA methylation and non-coding RNAs), and their inter-regulation involved in the pathogenesis of skeletal fluorosis. In this review, we summarised and analyzed relevant findings to provide a basis for comprehensive understandings of the pathogenesis of skeletal fluorosis and hopefully propose more effective prevention and therapeutic strategies.
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Enfermedades Óseas Metabólicas/patología , Metilación de ADN , Epigénesis Genética , Fluoruros/efectos adversos , Fluorosis Dental/patología , Estrés Fisiológico , Animales , Enfermedades Óseas Metabólicas/etiología , Enfermedades Óseas Metabólicas/metabolismo , Fluorosis Dental/etiología , Fluorosis Dental/metabolismo , Humanos , Transducción de SeñalRESUMEN
Organic dyes emitting in the second near-infrared (NIR-II, 900-1700â nm) window, with high molar extinction coefficients (MEC) and quantum yields (QY) in aqueous, are essential for inâ vivo bioimaging and biosensing. In this work, we developed a dibodipy-based aggregation-induced emission (AIE) fluorescent probe, THPP, to meet this aim. THPP exhibits a high MEC and has intensified absorption and emission in J-aggregated state, which significantly enhance the fluorescence intensity (≈55 folds) and extend the maximal absorption/emission wavelengths to 970/1010â nm in NIR-II region. Based on the bright THPP, imaging with a high frame rate (34 frames per second) at a deep "valid penetration depth" up to 6â mm can be achieved. This enabled simultaneous and dynamic imaging of vasculatures and deep tissues. Besides, we succeeded in monitoring the respiratory rate of acute-lung-injury mice and tracing the collateral circulation process with a high frame rate.
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Colorantes Fluorescentes/química , Imagen Óptica/métodos , Propiofenonas/química , Lesión Pulmonar Aguda/diagnóstico por imagen , Animales , Materiales Biocompatibles/química , Venas Cerebrales/diagnóstico por imagen , Ratones , Micelas , Nanopartículas/química , Teoría Cuántica , Relación Señal-Ruido , Espectroscopía Infrarroja CortaRESUMEN
BACKGROUND: Based on its low toxicity, arginine starvation therapy has the potential to cure malignant tumors that cannot be treated surgically. The Arginine deiminase (ADI) gene has been identified to be an ideal cancer-suppressor gene. ADI expressed in the cytosol displays higher oncolytic efficiency than ADI-PEG20 (Pegylated Arginine Deiminase by PEG 20,000). However, it is still unknown whether cytosolic ADI has the same mechanism of action as ADI-PEG20 or other underlying cellular mechanisms. METHODS: The interactions of ADI with other protein factors were screened by yeast hybrids, and verified by co-immunoprecipitation and immunofluorescent staining. The effect of ADI inhibiting the ferritin light-chain domain (FTL) in mitochondrial damage was evaluated by site-directed mutation and flow cytometry. Control of the mitochondrial apoptosis pathway was analyzed by Western Blotting and real-time PCR experiments. The effect of p53 expression on cancer cells death was assessed by siTP53 transfection. Chromatin autophagy was explored by immunofluorescent staining and Western Blotting. RESULTS: ADI expressed in the cytosol inhibited the activity of cytosolic ferritin by interacting with FTL. The inactive mutant of ADI still induced apoptosis in certain cell lines of ASS- through mitochondrial damage. Arginine starvation also generated an increase in the expression of p53 and p53AIP1, which aggravated the cellular mitochondrial damage. Chromatin autophagy appeared at a later stage of arginine starvation. DNA damage occurred along with the entire arginine starvation process. Histone 3 (H3) was found in autophagosomes, which implies that cancer cells attempted to utilize the arginine present in histones to survive during arginine starvation. CONCLUSIONS: Mitochondrial damage is the major mechanism of cell death induced by cytosolic ADI. The process of chromatophagy does not only stimulate cancer cells to utilize histone arginine but also speeds up cancer cell death at a later stage of arginine starvation.
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Cromatina/metabolismo , Ferritinas/metabolismo , Hidrolasas/metabolismo , Mitocondrias/patología , Neoplasias/patología , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Arginina/metabolismo , Autofagia/efectos de los fármacos , Autofagia/fisiología , Línea Celular Tumoral , Citosol/metabolismo , Histonas/metabolismo , Humanos , Hidrolasas/farmacología , Hidrolasas/uso terapéutico , Mitocondrias/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Polietilenglicoles/farmacología , Polietilenglicoles/uso terapéuticoRESUMEN
A 2D conjugated polyelectrolyte (CPE), PBDTTh-TT-NBr, having the same backbone as the highly efficient donor polymer PTB7-Th and the quaternary ammonium pendant, is synthesized as a cathode interlayer (CIL) material for PTB7-Th-based fullerene and non-fullerene solar cells. The quaternary ammonium group is connected to the 2D conjugated backbone by a long, flexible alkyl chain, facilitating the modification of cathode via forming interface dipoles. Moreover, compared with another CPE analogue to PTB7, PBDT-TT-NBr, without the 2D conjugated backbone, the PBDTTh-TT-NBr presents a higher similarity in polymer structure to the donor polymer PTB7-Th. This feature makes it more compatible with the PTB7-Th-based active-layer film, improving the electron transport. With the PBDTTh-TT-NBr as the CIL, devices afford higher performances than those using the PBDT-TT-NBr in both fullerene and non-fullerene systems. This work offers guidance on choosing the CIL material that ought to possess a highly similar structure to the active-layer component.
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Polielectrolitos/química , Polímeros/química , Polímeros/síntesis química , Compuestos de Amonio/química , Electrodos , Transporte de Electrón , Fulerenos/química , Microscopía de Fuerza Atómica , Energía Solar , Luz Solar , Propiedades de SuperficieRESUMEN
Shape-stabilized phase change material (SSPCM) is a promising thermal energy storage material in energy-saving buildings. However, its flammability leads to a fire risk. The conventional bulk addition method has a limited flame-retardant effect. Herein, a series of surface coatings with various flame retardants were introduced to improve flame retardance of SSPCM. The results showed that all of the coatings had flame-retardant effects on SSPCM; In particular, the EG coating performed the best: the horizontal burning time was the longest, the limiting oxygen index was above 30%, the V0 classification was obtained, the peak heat release rate was sharply decreased from 1137.0 to 392.5 kW/m2 and the burning process was prolonged with the least total smoke production. The flame-retardant mechanism was discussed. As paraffin easily evaporated from the SSPCM at a moderate temperature, it caused flames. After being surface coated, the EG-based coatings first hindered the volatilization of paraffin at a moderate temperature, then expanded and formed thick porous carbon layers at a high temperature to block the transfer of combustibles, oxygen and heat between the bulk and the environment. Therefore, the surface coating strategy achieved a desirable flame-retardant level with fewer flame retardants.
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Materiales Biocompatibles Revestidos/química , Retardadores de Llama , Grafito/química , Parafina/química , Calor/efectos adversos , Propiedades de SuperficieRESUMEN
Coadministration of chemotherapeutics as well as therapeutic gene could play a synergistic effect on cancer treatment. It is noteworthy that targeted and sustained codelivery of chemotherapeutic and therapeutic gene was rarely achieved in previous reports, while it might serve as an important platform for treating solid tumor with possible surrounding lesions. Herein, an injectable supramolecular hydrogel formed by α-cyclodextrin (α-CD) and cationic amphiphilic copolymer made of methoxy-poly(ethylene glycol)-b-poly(ε-caprolactone)-b-poly(ethylene imine) with folic acid targeted group (MPEG-PCL-PEI-FA), is rationally designed to achieve sustained codelivery of chemotherapeutic paclitaxel (PTX) and B-cell lymphoma-2 (Bcl-2) conversion gene Nur77 in the form of nanocomplex up to 7 days, to effectively inhibit the growth of folate receptor overexpressing H460/Bcl-2 therapeutic-resistant tumors (induced by overexpression of anti-apoptotic Bcl-2 protein), with peritumoral injection rather than direct intratumoral injection of hydrogel. To the best of our knowledge, this is a pioneer report on injectable MPEG-PCL-PEI-FA/α-CD supramolecular hydrogel with the ability to codeliver and sustainedly release PTX and Nur77 gene to combat Bcl-2 overexpressed therapeutic-resistant tumors in a targeted manner, which might be beneficial for further design in personalized medicine.
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Antineoplásicos/uso terapéutico , Resistencia a Antineoplásicos , Técnicas de Transferencia de Gen , Hidrogeles/química , Inyecciones , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/administración & dosificación , Cationes , Línea Celular Tumoral , Preparaciones de Acción Retardada , Ácido Fólico/química , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias/patología , Poliésteres , Polietilenglicoles , Polietileneimina/química , Tensoactivos/químicaRESUMEN
The resistance developed by life-threatening bacteria toward conventional antibiotics has become a major concern in public health. To combat antibiotic resistance, there has been a significant interest in the development of antimicrobial cationic polymers due to the ease of synthesis and low manufacturing cost compared to host-defense peptides (HDPs). Herein, we report the design and synthesis of amphiphilic polycarbonates containing primary amino groups. These polymers exhibit potent antimicrobial activity and excellent selectivity to Gram-positive bacteria, including multidrug resistant pathogens. Fluorescence and TEM studies suggest that these polymers are likely to kill bacteria by disrupting bacterial membranes. These polymers also show low tendency to elicit resistance in bacteria. Their further development may lead to new antimicrobial agents combating drug-resistance.
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Antiinfecciosos/farmacología , Bacterias Grampositivas/efectos de los fármacos , Cemento de Policarboxilato/farmacología , Polímeros/farmacología , Antiinfecciosos/química , Humanos , Pruebas de Sensibilidad Microbiana , Cemento de Policarboxilato/química , Polímeros/químicaRESUMEN
BACKGROUND & AIMS: Telaprevir plus pegylated interferon/ribavirin (TPV+PegIFN/RBV) remains a therapeutic option for chronic hepatitis C virus (HCV) genotype (GT) 1 infection in many regions. We conducted two open-label, phase IIIb trials comparing safety and efficacy of all-oral ombitasvir/paritaprevir/ritonavir and dasabuvir±ribavirin (OBV/PTV/r+DSV±RBV) and TPV+PegIFN/RBV. METHODS: Treatment-naïve (MALACHITE-I) or PegIFN/RBV-experienced (MALACHITE-II) non-cirrhotic, chronic HCV GT1-infected patients were randomized to OBV/PTV/r+DSV+weight-based RBV, OBV/PTV/r+DSV (treatment-naïve, GT1b-infected patients only), or 12weeks of TPV+PegIFN+weight-based RBV and 12-36 additional weeks of PegIFN/RBV. The primary endpoint was sustained virologic response 12weeks post-treatment (SVR12). Patient-reported outcome questionnaires evaluated mental and physical health during the studies. RESULTS: Three hundred eleven treatment-naïve and 148 treatment-experienced patients were randomized and dosed. Among treatment-naïve patients, SVR12 rates were 97% (67/69) and 82% (28/34), respectively, in OBV/PTV/r+DSV+RBV and TPV+PegIFN/RBV-treated GT1a-infected patients; SVR12 rates were 99% (83/84), 98% (81/83), and 78% (32/41) in OBV/PTV/r+DSV+RBV, OBV/PTV/r+DSV, and TPV+PegIFN/RBV-treated GT1b-infected patients. Among treatment-experienced patients, SVR12 rates were 99% (100/101) and 66% (31/47) with OBV/PTV/r+DSV+RBV and TPV+PegIFN/RBV. Mental and physical health were generally better with OBV/PTV/r+DSV±RBV than TPV+PegIFN/RBV. Rates of discontinuation due to adverse events (0-1% and 8-11%, respectively, p<0.05) and rates of hemoglobin decline to <10g/dl (0-4% and 34-47%, respectively, p<0.05) were lower for OBV/PTV/r+DSV±RBV than TPV+PegIFN/RBV. CONCLUSIONS: Among non-cirrhotic, HCV GT1-infected patients, SVR12 rates were 97-99% with 12week, multi-targeted OBV/PTV/r+DSV±RBV regimens and 66-82% with 24-48 total weeks of TPV+PegIFN/RBV. OBV/PTV/r+DSV±RBV was associated with a generally better mental and physical health, more favorable tolerability, and lower rates of treatment discontinuation due to adverse events.
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Anilidas/administración & dosificación , Antivirales/administración & dosificación , Carbamatos/administración & dosificación , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Compuestos Macrocíclicos/administración & dosificación , Sulfonamidas/administración & dosificación , Uracilo/análogos & derivados , 2-Naftilamina , Adulto , Anciano , Anilidas/efectos adversos , Carbamatos/efectos adversos , Ciclopropanos , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/clasificación , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Lactamas Macrocíclicas , Compuestos Macrocíclicos/efectos adversos , Masculino , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Prolina/análogos & derivados , Proteínas Recombinantes/administración & dosificación , Sulfonamidas/efectos adversos , Uracilo/administración & dosificación , Uracilo/efectos adversos , ValinaRESUMEN
Hypotonia, Ataxia, Developmental Delay, and Tooth Enamel Defect Syndrome (HADDTS) is an exceptionally rare disorder resulting from a heterozygous variant in the C-terminal binding protein 1 (CTBP1) gene. To date, a mere two variants (14 patients) have been documented on a global scale. The aim of this study was to identify a causative CTBP1 variant in a Chinese patient, and to determine the potential pathogenicity of the identified variant. Here, Whole-exome sequencing (WES) was conducted on the proband to pinpoint the candidate variant. Following this, Sanger sequencing was employed to validate the identified candidate variant and examine its co-segregation within the available family members. Employing both in silico prediction and three-dimensional protein modeling, we conducted an analysis to assess the potential functional implications of the variant on the encoded protein. Our investigation led to the identification of a novel heterozygous variant in the CTBP1 gene, namely, c.371 C>T (p.Ser124Phe), in a Chinese patient. This case represents the first confirmed instance of such a variant in a Chinese patient. When comparing the patient's clinical symptoms with those reported in the literature, notable distinctions were observed between her primary symptoms and those associated with HADDTS. She showed other signs such as microcephaly, coarse facial features, single transverse palmar crease, visible beard, myopia, coarse toenail and skeletal anomalies. This study enriching the spectrum of genetic variants observed in different ethnic populations and expanding the phenotypic profile associated with this gene. These findings are expected to contribute to the enhancement of future variant-based screening and genetic diagnosis, while also providing further insights into the pathogenic mechanisms underlying CTBP1-related conditions.
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Traditional signal processing methods based on acceleration signals can determine whether a fault has occurred in a planetary gearbox. However, acceleration signals are severely affected by interference, causing difficulties in fault identification. This study proposes a gear fault classification method based on root strain and pseudo images. Firstly, fiber optic sensors are employed to directly acquire strain data from the ring gear root. Next, the strain signals are preprocessed using resampling and a time-domain synchronous averaging algorithm. The processed signals are encoded into two-dimensional images using Gramian Angular Fields (GAF). Then, CN-EfficientNet with contrast learning is proposed to analyze and extract deeper fault features from the image texture features. In the classification experiments for different types of faults, the accuracy reached 96.84%. The results indicate that the method can effectively accomplish the task of fault classification in planetary gearboxes. Comparative experiments with other common classification models further indicate the superior performance of the proposed learning model. Visualization based on Grad-CAM provides interpretability for the fault recognition network's results and reveals the underlying mechanism for its excellent classification performance.
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Plastic pollution in aquatic environments poses significant concerns due to its potential to serve as a refuge for aquatic pathogens. However, the role of plastic surfaces and microbial biofilm interfaces in facilitating pathogen development remains poorly understood. In this study, a microcosm setup was employed to investigate the interactions between plastics and the microbial community and examine the differences in bacterial community composition and potential pathogen occurrences between the plastisphere-biofilm and surrounding seawater. Community composition analysis combined with SEM observations over time indicated that biofilm extracellular polymeric substance formation over 14 days had a link with the relative abundance and succession patterns of pathogen taxa. Colony clusters were observed on biofilms from day 7 and coincided with higher bacterial pathogen dominance. On day 14, pathogen abundance overall decreased with a potentially degrading biofilm. Pseudomonas and Pseudoalteromonas were the dominant potential pathogen groups observed in the microcosm. When further subjected to chemical treatment as an imposed environmental stress over time, biofilm-associated Psuedoalteromonas sharply increased in abundance after three days of exposure, but quickly diminished by 14 days in favor of genera such as Acinetobacter, Pseudomonas, and Staphylococcus. These results suggest that environmental plastisphere-biofilms can promote the early selection, enrichment, and spread of pathogenic bacteria in the aquatic environment and could be later worsened under chemical and long-term pressure. This study provided new insights into the succession of pathogens in plastisphere biofilms, contributing to the understanding of pathogen risks involved in emerging plastisphere biofilms in light of global plastic pollution.
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Matriz Extracelular de Sustancias Poliméricas , Plásticos , Polímeros , Bacterias , Agua de Mar/microbiologíaRESUMEN
We present a triple-mode nanosensor platform for nucleic acid detection utilizing fluorescence anisotropy and Förster resonance energy transfer (FRET) strategies. The self-assembled nanoprobes serve as mass amplifiers, nanoquenchers, or nanodonors, exhibiting high FRET efficiencies (64.4-86.5%) and demonstrating excellent detection capabilities in DNA and microRNA analysis.
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ADN , Transferencia Resonante de Energía de Fluorescencia , MicroARNs , Polímeros , ADN/química , Polímeros/química , MicroARNs/análisis , Colorantes Fluorescentes/química , Polarización de Fluorescencia , Fluorescencia , Técnicas Biosensibles/métodosRESUMEN
Oral and maxillofacial tumors pose a significant clinical challenge due to their tendency to recur, despite advancements in surgical removal techniques. The jaw's intricate structure further complicates treatments and affects patient quality of life. Consequently, emphasis has shifted towards pharmacological interventions, to potentially reduce invasive surgical procedures. One promising approach targets BRAF mutations, specifically the common V600E mutation. BRAF, a critical protein kinase, regulates cell growth and differentiation via the RAS-RAF-MEK-ERK-MAP kinase pathway. A specific nucleotide change at position 1799, swapping Thymine (T) for Adenine (A), results in the V600E mutation, causing unchecked cell growth. This mutation is common in certain oral and maxillofacial tumors like ameloblastoma. A recent neoadjuvant therapy targeting BRAF, involving the use of dabrafenib and trametinib, has showcased a promising, safe, and effective strategy for organ preservation in the treatment of mandibular ameloblastoma. This convergence of molecular insights and targeted therapies holds the key to managing BRAF-mutated oral and maxillofacial tumors effectively, promising improved patient outcomes.
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Ameloblastoma , Mutación , Proteínas Proto-Oncogénicas B-raf , Humanos , Proteínas Proto-Oncogénicas B-raf/genética , Ameloblastoma/genética , Ameloblastoma/terapia , Ameloblastoma/diagnóstico , Imidazoles/uso terapéutico , Oximas/uso terapéutico , Piridonas/uso terapéutico , Piridonas/administración & dosificación , Pirimidinonas/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Boca/terapia , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Terapia Neoadyuvante/métodos , Terapia Molecular DirigidaRESUMEN
Wound management is a major challenge worldwide, placing a huge financial burden on the government of every nation. Wound dressings that can protect wounds, accelerate healing, prevent infection, and avoid secondary damage continue to be a major focus of research in the health care and clinical communities. Herein, a novel zwitterionic polymer (LST) hydrogel incorporated with [2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide (SBMA), mussel-inspired N-[tris(hydroxymethyl)methyl] acrylamide (THMA), and lithium magnesium salt was prepared for functional wound dressings. The incorporation of the THMA monomer containing three hydroxyl groups gives the hydrogel suitable adhesion properties (â¼6.0 KPa). This allows the LST zwitterionic hydrogels to bind well to the skin, which not only protects the wound and ensures its therapeutic efficacy but also allows for painless removal and reduced patient pain. Zwitterionic sulfobetaine units of SBMA provide antimicrobial and mechanical properties. The chemical structure and microscopic morphology of LST zwitterionic hydrogels were systematically studied, along with their swelling ratio, adhesion, and mechanical properties. The results showed that the LST zwitterionic hydrogels had a uniform and compact porous structure with the highest swelling and mechanical strain of 1607% and 1068.74%, respectively. The antibacterial rate of LST zwitterionic hydrogels was as high as 99.49%, and the hemostatic effect was about 1.5 times that of the commercial gelatin hemostatic sponges group. In further studies, a full-thickness mouse skin model was selected to evaluate the wound healing performance. Wounds covered by LST zwitterionic hydrogels had a complete epithelial reformation and new connective tissue, and its vascular regenerative capacity was increased to about 2.4 times that of the commercial group, and the wound could completely heal within 12-13 days. This study provides significant advances in the design and construction of multifunctional zwitterionic hydrogel adhesives and wound dressings.
Asunto(s)
Antibacterianos , Hidrogeles , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Animales , Ratones , Antibacterianos/química , Antibacterianos/farmacología , Hemostáticos/química , Hemostáticos/farmacología , Vendajes , Adhesivos/química , Adhesivos/farmacología , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Hemostasis/efectos de los fármacos , Polímeros/química , Polímeros/farmacologíaRESUMEN
Microplastics have emerged as a prominent global environmental contaminant, and they have been found in both human placenta and breast milk. However, the potential effects and mechanisms of maternal exposure to microplastics at various gestational stages on offspring neurodevelopment remain poorly understood. This investigation delves into the potential neurodevelopmental ramifications of maternal exposure to polystyrene nanoplastics (PS-NPs) during distinct phases of pregnancy and lactation. Targeted metabolomics shows that co-exposure during both pregnancy and lactation primarily engendered alterations in monoamine neurotransmitters within the cortex and amino acid neurotransmitters within the hippocampus. After prenatal exposure to PS-NPs, fetal rats showed appreciably diminished cortical thickness and heightened cortical cell proliferation. However, this exposure did not affect the neurodifferentiation of radial glial cells and intermediate progenitor cells. In addition, offspring are accompanied by disordered neocortical migration, typified by escalated superficial layer neurons proliferation and reduced deep layer neurons populations. Moreover, the hippocampal synapses showed significantly widened synaptic clefts and diminished postsynaptic density. Consequently, PS-NPs culminated in deficits in anxiolytic-like behaviors and spatial memory in adolescent offspring, aligning with concurrent neurotransmitter and synaptic alterations. In conclusion, this study elucidates the sensitive windows of early-life nanoplastic exposure and the consequential impact on offspring neurodevelopment.