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Super-resolution imaging has rapidly emerged as an optical microscopy technique, offering advantages of high optical resolution over the past two decades; achieving improved imaging resolution requires significant efforts in developing super-resolution imaging agents characterized by high brightness, high contrast and high sensitivity to fluorescence switching. Apart from technical requirements in optical systems and algorithms, super-resolution imaging relies on fluorescent dyes with special photophysical or photochemical properties. The concept of aggregation-induced emission (AIE) was proposed in 2001, coinciding with unprecedented advancements and innovations in super-resolution imaging technology. AIE probes offer many advantages, including high brightness in the aggregated state, low background signal, a larger Stokes shift, ultra-high photostability, and excellent biocompatibility, making them highly promising for applications in super-resolution imaging. In this review, we summarize the progress in implementation methods and provide insights into the mechanism of AIE-based super-resolution imaging, including fluorescence switching resulting from photochemically-converted aggregation-induced emission, electrostatically controlled aggregation-induced emission and specific binding-regulated aggregation-induced emission. Particularly, the aggregation-induced emission principle has been proposed to achieve spontaneous fluorescence switching, expanding the selection and application scenarios of super-resolution imaging probes. By combining the aggregation-induced emission principle and specific molecular design, we offer some comprehensive insights to facilitate the applications of AIEgens (AIE-active molecules) in super-resolution imaging.
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Recent work has revealed that spontaneous release plays critical roles in the central nervous system, but how it is regulated remains elusive. Here, we report that synaptotagmin-11 (Syt11), a Ca2+ -independent Syt isoform associated with schizophrenia and Parkinson's disease, suppressed spontaneous release. Syt11-knockout hippocampal neurons showed an increased frequency of miniature excitatory post-synaptic currents while over-expression of Syt11 inversely decreased the frequency. Neither knockout nor over-expression of Syt11 affected the average amplitude, suggesting the pre-synaptic regulation of spontaneous neurotransmission by Syt11. Glutathione S-transferase pull-down, co-immunoprecipitation, and affinity-purification experiments demonstrated a direct interaction of Syt11 with vps10p-tail-interactor-1a (vti1a), a non-canonical SNARE protein that maintains spontaneous release. Importantly, knockdown of vti1a reversed the phenotype of Syt11 knockout, identifying vti1a as the main target of Syt11 inhibition. Domain analysis revealed that the C2A domain of Syt11 bound vti1a with high affinity. Consistently, expression of the C2A domain alone rescued the phenotype of elevated spontaneous release in Syt11-knockout neurons similar to the full-length protein. Altogether, our results suggest that Syt11 inhibits vti1a-containing vesicles during spontaneous release.
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Proteínas Qb-SNARE/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , Sinaptotagminas/farmacología , Animales , Fenómenos Electrofisiológicos , Potenciales Postsinápticos Excitadores , Técnicas de Sustitución del Gen , Hipocampo/patología , Inmunoprecipitación , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neuronas/patología , Cultivo Primario de CélulasRESUMEN
A water-soluble probe, TPA-1OH, with aggregation-induced emission activity is synthesized and used for expedient real-time fluorescence in situ visualization of latent fingerprints (LFPs). A TPA-1OH aqueous solution exhibits nonfluorescence in pure water while strong fluorescence upon molecular aggregation induced by addition of poor solvent. Fluorescence images of LFPs on a variety of substrates, including rough surfaces such as walls, bricks, and paper, are developed under 405 nm light, by soaking in or spraying with a TPA-1OH aqueous solution (30 µM) without any necessity of organic cosolvents and post-treatment steps. The probe is noncytotoxic at a concentration lower than 50 µM. The development process of LFPs is demonstrated by real-time fluorescence in situ imaging. The exponential relationship between the relative fluorescence intensity and time is deduced from the fitting curve. The LFP images developed by TPA-1OH are evident and intact enough to allow that the level 1-3 details are displayed and analyzed. Noteworthily, the level 3 details of LFPs such as the fingerprint ridge width and the characteristics of the sweat pores are evidently visible under fluorescence microscopy. Even the nanoscopic details exceeding level 3 are visualized under super-resolution microscopy with sub-50 nm optical resolution.
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Women with polycystic ovary syndrome (PCOS) are characterized by endocrine disorders accompanied by a decline in oocyte quality. In this study, we generated a PCOS mice model by hypodermic injection of dehydroepiandrosterone, and metformin was used as a positive control drug to study the effect of pachymic acid (PA) on endocrine and oocyte quality in PCOS mice. Compared with the model group, the mice treated with PA showed the following changes (slower weight gain, improved abnormal metabolism; increased development potential of GV oocytes, reduced number of abnormal MII oocytes, and damaged embryos; lower expression of ovarian-related genes in ovarian tissue and pro-inflammatory cytokines in adipose tissue). All these aspects show similar effects on metformin. Most notably, PA is superior to metformin in improving inflammation of adipose tissue and mitochondrial abnormalities. It is suggested that PA has the similar effect with metformin, which can improve the endocrine environment and oocyte quality of PCOS mice. These findings suggest that PA has the similar effect with metformin, which can improve the endocrine environment and oocyte quality of PCOS mice.
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Oocitos/efectos de los fármacos , Ovario/efectos de los fármacos , Síndrome del Ovario Poliquístico/metabolismo , Triterpenos/farmacología , Animales , Deshidroepiandrosterona , Modelos Animales de Enfermedad , Femenino , Metformina/farmacología , Ratones , Oocitos/metabolismo , Ovario/metabolismo , Síndrome del Ovario Poliquístico/inducido químicamenteRESUMEN
Protein misfolding and denaturation, represented by amyloid fibrillation, are associated with many diseases. However, as a general chemical biological process, the dynamic structure information on amyloid fibrillation has not been demonstrated categorically. Herein, hen egg white lysozyme (HEWL) was used as the model protein of interest to realize in situ nanoscale imaging of protein fibrillation process using the fluorophores with aggregation-induced emission (AIE) activity. The AIE-active fluorophores exhibit the reversible capability of association and dissociation with ß-sheet structure and thus dynamic binding-induced emission, which causes the spontaneous switching of fluorescence. The entire HEWL denaturation process induced by sodium dodecyl sulfate (SDS) at ambient conditions was demonstrated in detail by using two AIE-active fluorophores (TPE-NaSO3 and PD-BZ-OH) through reversible electrostatic interaction and specific labeling between AIE probes and ß-sheet structures of amyloid fibrils, respectively. The results indicate that PD-BZ-OH is more specific AIE probe for amyloid fibrils than TPE-NaSO3. In comparison, the SEM and TEM results show the same denaturation process of protein fibrillation induced by SDS at different concentrations. The static super-resolution imaging of amyloid fibrils is performed with a resolution of 35 nm using PD-BZ-OH aqueous solution without additional auxiliary conditions. The dynamic evolution process of HEWL amyloid fibrillation is in situ visualized through super-resolution fluorescent microscopy with nanoscale resolution. Both static and dynamic super-resolution imaging of amyloid fibrillation provides detailed nanoscale structure information exceeding 50 nm resolution, which is of great significance in the exploration of amyloid fibrillation and related diseases.
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Amiloide/química , Muramidasa/química , Agregado de Proteínas , Amiloide/ultraestructura , Animales , Pollos , Citrulinación , Clara de Huevo/química , Conformación Proteica en Lámina betaRESUMEN
Recently, graphene nanomaterials have attracted tremendous attention and have been utilized in various fields because of their excellent mechanical, thermal, chemical, optical properties, and good biocompatibility, especially in biomedical aspects. However, there is a concern that the unique characteristics of nanomaterials may have undesirable effects. Therefore, in this study, we sought to systematically investigate the effects of graphene quantum dots (GQDs) on the maturation of mouse oocytes and development of the offspring via in vitro and in vivo studies. In vitro, we found that the first polar body extrusion rate in the high dosage exposure groups (1.0-1.5 mg/ml) 2 decreased significantly and the failure of spindle migration and actin cap formation after GQDs exposure was observed. The underlying mechanisms might be associated with reactive oxygen species accumulation and DNA damage. Moreover, transmission electron microscope studies showed that GQDs may have been internalized into oocytes, tending to accumulate in the nucleus and severely affecting mitochondrial morphology, which included swollen and vacuolated mitochondria accompanied by cristae alteration with a lower amount of dense mitochondrial matrix. In vivo, when pregnant mice were exposed to GQDs at 8.5 days of gestation (GD, 8.5), we found that high dosage of GQD exposure (30 mg/kg) significantly affected mean fetal length; however, all the second generation of female mice grew up normal, attained sexual maturity, and gave birth to a healthy offspring after mating with a healthy male mouse. The results presented in this study are important for the future investigation of GQDs for the biomedical applications.
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Desarrollo Embrionario/efectos de los fármacos , Grafito/farmacología , Oocitos/citología , Puntos Cuánticos/química , Actinas/metabolismo , Animales , Roturas del ADN de Doble Cadena/efectos de los fármacos , Femenino , Feto/efectos de los fármacos , Feto/embriología , Masculino , Metafase/efectos de los fármacos , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/ultraestructura , Oocitos/efectos de los fármacos , Oocitos/metabolismo , Oocitos/ultraestructura , Puntos Cuánticos/ultraestructura , Especies Reactivas de Oxígeno/metabolismo , Huso Acromático/efectos de los fármacos , Huso Acromático/metabolismo , Difracción de Rayos XRESUMEN
In chemical synapses, action potentials evoke synaptic vesicle fusion with the presynaptic membrane at the active zone to release neurotransmitter. Synaptic vesicle endocytosis (SVE) then follows exocytosis to recapture vesicle proteins and lipid components for recycling and the maintenance of membrane homeostasis. Therefore, SVE plays an essential role during neurotransmission and is one of the most precisely regulated biological processes. Four modes of SVE have been characterized and both positive and negative regulators have been identified. However, our understanding of SVE regulation remains unclear, especially the identity of negative regulators and their mechanisms of action. Here, we review the current knowledge of proteins that function as inhibitors of SVE and their modes of action in different forms of endocytosis. We also propose possible physiological roles of such negative regulation. We believe that a better understanding of SVE regulation, especially the inhibitory mechanisms, will shed light on neurotransmission in health and disease.
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Endocitosis , Mapas de Interacción de Proteínas , Vesículas Sinápticas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Calcineurina/metabolismo , Calpaína/metabolismo , Quinasa 5 Dependiente de la Ciclina/metabolismo , Humanos , Sinapsis/metabolismo , Transmisión Sináptica , Sinaptotagminas/metabolismo , TemperaturaRESUMEN
Methoxychlor (MXC) is used worldwide against insects and other pests. This organochlorine pesticide acts as a xenoestrogen, promotes oxidative stress, and is considered cytotoxic and genotoxic, causing abortions and stillbirths in females. Mechanistically related estrogens and oxidants affect oocyte meiosis, so we investigated the effects of MXC on mouse oocyte meiotic maturation. Our results showed that maturation rates of MXC-treated oocytes were lower than those of controls, which was due to abnormal spindle morphologies and DNA double-strand breaks, as confirmed by increased γ-H2AX foci. Our findings also suggest that MXC may affect oocyte quality by causing the accumulation of superoxide radicals and other reactive oxygen species, aberrant mitochondrial distribution, decreased mitochondrial membrane potential, and increased lipid peroxidation. Thus, exposure to MXC negatively affects oocyte meiotic maturation, primarily through impairments in cellular ROS metabolism. Mol. Reprod. Dev. 83: 768-779, 2016 © 2016 Wiley Periodicals, Inc.
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Roturas del ADN de Doble Cadena , Meiosis/efectos de los fármacos , Metoxicloro/efectos adversos , Oocitos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Superóxidos/metabolismo , Animales , Femenino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Metoxicloro/farmacología , Ratones , Ratones Endogámicos ICR , Oocitos/patologíaRESUMEN
Fluorescence sensing of latent fingerprints (LFPs) has gained extensive attention due to its high sensitivity, non-destructive testing, low biotoxicity, ease of operation, and the potential for in situ visualization. However, the realization of in situ visualization of LFPs especially with green emission and rapid speed is still a challenge. Herein, we synthesized an amphibious green-emission AIE-gen TPE-NI-AOH (PLQY = 62%) for instant in situ LFP detecting, which integrates the excellent fluorescence properties of naphthalimide (NI) with a hydrophilic head and the AIE character as well as the donating property of tetraphenylethene (TPE). TPE-NI-AOH in ethanol/water binary solvent was used as an environmentally friendly LFP developer and achieved in situ green-fluorescence visualization of LFPs. The fluorescence signal achieves its 60% saturated intensity in 0.37 s and nearly 100% in 2.50 s, which is an instant process for the naked eye. Moreover, level 3 details and super-resolution images of LFPs could be observed clearly. Besides, the TPE-NI-AOH developer could be stored for at least 6 months, suitable for long-term storage. This instant in situ highlighting method does not require post-processing operations, providing a more convenient, rapid, and efficient detection method of LFPs. This work would inspire the further advancement of fluorescent sensors for fingerprint imaging.
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Técnicas Biosensibles , Dermatoglifia , Colorantes Fluorescentes , Colorantes Fluorescentes/química , Humanos , Técnicas Biosensibles/métodos , Espectrometría de Fluorescencia/métodos , Estilbenos/química , Naftalimidas/químicaRESUMEN
BACKGROUND: Actinidia arguta leaves (AAL) are traditionally consumed as a vegetable and as tea in folk China and Korea. Previous studies have reported the anti-diabetic effect of AAL, but its bioactive components and mechanism of action are still unclear. AIM OF THE STUDY: This study aims to identify the hypoglycemic active components of AAL by combining serum pharmacochemistry and network pharmacology and to elucidate its possible mechanism of action. METHODS: Firstly, the effective components in mice serum samples were characterized by UPLC-Q/TOF-MSE. Furthermore, based on these active ingredients, network pharmacology analysis was performed to establish an "H-C-T-P-D" interaction network and reveal possible biological mechanisms. Finally, the affinity between serum AAL components and the main proteins in the important pathways above was investigated through molecular docking analysis. RESULTS: Serum pharmacochemistry analysis showed that 69 compounds in the serum samples were identified, including 23 prototypes and 46 metabolites. The metabolic reactions mainly included deglycosylation, dehydration, hydrogenation, methylation, acetylation, glucuronidation, and sulfation. Network pharmacology analysis showed that the key components quercetin, pinoresinol diglucoside, and 5-O-trans-p-coumaroyl quinic acid butyl ester mainly acted on the core targets PTGS2, HRAS, RELA, PRKCA, and BCL2 targets and through the PI3K-Akt signaling pathway, endocrine resistance, and MAPK signaling pathway to exert a hypoglycemic effect. Likewise, molecular docking results showed that the three potential active ingredients had good binding effects on the five key targets. CONCLUSION: This study provides a basis for elucidating the pharmacodynamic substance basis of AA against T2DM and further exploring the mechanism of action.
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Actinidia , Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Simulación del Acoplamiento Molecular , Farmacología en Red , Extractos Vegetales , Hojas de la Planta , Actinidia/química , Hojas de la Planta/química , Animales , Ratones , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Masculino , Cromatografía Líquida de Alta Presión/métodos , Transducción de Señal/efectos de los fármacosRESUMEN
Hydrogel is considered as a promising candidate for wound dressing due to its tissue-like flexibility, good mechanical properties and biocompatibility. However, traditional hydrogel dressings often fail to fulfill satisfied mechanical, antibacterial, and biocompatibility properties simultaneously, due to the insufficient intrinsic bactericidal efficacy and the addition of external antimicrobial agents. In this paper, hydroxyl-contained acrylamide monomers, N-Methylolacrylamide (NMA) and N-[Tris (hydroxymethyl)methyl] acrylamide (THMA), are employed to prepare a series of polyacrylamide hydrogel dressings xNMA-yTHMA, where x and y represent the mass fractions of NMA and THMA in the hydrogels. We have elucidated that the abundance of hydroxyl groups determines the antibacterial effect of the hydrogels. Particularly, hydrogel 35NMA-5THMA exhibits excellent mechanical properties, with high tensile strength of 259 kPa and large tensile strain of 1737%. Furthermore, the hydrogel dressing 35NMA-5THMA demonstrates remarkable inherent antibacterial without exogenous antimicrobial agents owing to the existence of abundant hydroxyl groups. Besides, hydrogel dressing 35NMA-5THMA possesses excellent biocompatibility, in view of marginal cytotoxicity, low hemolysis ratio, and negligible inflammatory response and organ toxicity to mice during treatment. Encouragingly, hydrogel 35NMA-5THMA drastically promote the healing of bacteria-infected wound in mice. This study has revealed the importance of polyhydroxyl in the antibacterial efficiency of hydrogels and provided a simplified strategy to design wound healing dressings with translational potential.
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Atrazine is a widely used herbicide in agricultural production. Previous studies have shown that atrazine affects hormone secretion and oocyte maturation in female reproduction. However, the specific mechanism by which atrazine affects ovarian function remains unclear. In this study, using a mouse gastric lavage model, we report that four weeks of atrazine exposure affects body growth, interferes with the estrous cycle, and increases the number of atretic follicles in mice. The expression levels of follicle development related factors StAR, BMP15, and AMH decreased. Metabolomic analysis revealed that atrazine activates an inflammatory response in ovarian tissue. Further studies confirmed that the expression levels of TNF-α, IL-6, and NF-κB increased in the ovaries of mice exposed to atrazine. Additionally, α-smooth muscle actin (α-SMA) accumulated in ovarian tissue, and transforming growth factor-ß (TGF-ß) signaling was activated, indicating the occurrence of tissue fibrosis. Moreover, mice exposed to atrazine produced fewer oocytes and exhibited reduced embryonic development. Furthermore, mice exposed to atrazine exhibited altered gut microbiota abundance and a disrupted colon barrier. Collectively, these findings suggest that atrazine exposure induces ovarian inflammation and fibrosis, disrupts ovarian homeostasis, and impairs follicle maturation, ultimately reducing oocyte quality.
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Alzheimer's disease (AD) is a neurodegenerative disease. Due to its complex pathological mechanism, its etiology is not yet clear. As one of the main pathological markers of AD, amyloid-ß (Aß) plays an important role in the development of AD. The deposition of Aß is not only related to the degeneration of neurons, but also can activate a series of pathological events, including the activation of astrocytes and microglia, the breakdown of the blood-brain barrier, and the change in microcirculation, which is the main cause of brain lesions and death in AD patients. Therefore, the development of efficient and reliable Aß-specific probes is crucial for the early diagnosis and treatment of AD. This paper focuses on reviewing the application of small-molecule fluorescent probes in Aß imaging in vivo in recent years. These probes efficiently map the presence of Aß in vivo, providing a pathway for the early diagnosis of AD and providing enlightenment for the design of Aß-specific probes in the future.
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Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Humanos , Colorantes Fluorescentes , Enfermedades Neurodegenerativas/metabolismo , Encéfalo/metabolismo , Péptidos beta-Amiloides , Enfermedad de Alzheimer/diagnóstico por imagenRESUMEN
Leucine aminopeptidase (LAP) is an important protease that can specifically hydrolyze Leucine residues. LAP occurs in microorganisms, plants, animals, and humans and is involved in a variety of physiological processes in the human body. In the physiological system, abnormal levels of LAP are associated with a variety of diseases and pathological processes, such as cancer and drug-induced liver injury; thus, LAP was chosen as the early biochemical marker for many physiological processes, including cancer. Considering the importance of LAP in physiological and pathological processes, it is critical that high-efficiency and dependable technology be developed to monitor LAP levels. Herein, we summarize the organic small molecule fluorescence/chemiluminescence probes used for LAP detection in recent years, which can image LAP in cancer, drug-induced liver injury (DILI), and bacteria. It can also reveal the role of LAP in tumors and differentiate the serum of cirrhotic, drug-induced liver injury and normal models.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Neoplasias , Animales , Humanos , Colorantes Fluorescentes/química , Leucil Aminopeptidasa/química , Imagen ÓpticaRESUMEN
The efficient development of latent fingerprint (LFP) is attractively important for criminal investigation. The low-cost and high-contrast developer is still a challenge. In this study, we designed and synthesized dicyanomethylene-4H-pyran (DCM) derivatives PZ-DCM and Boc-PZ-DCM by introducing of large steric hindrance group Boc, the solid-state fluorescence of DCM derivatives was greatly enhanced. The low-cost fluorescent LFP developers were prepared by blending with different proportion of montmorillonite (MMT). As a result, clear and high contrast fingerprint patterns were obtained with dusting method by the developer with 3% content of Boc-PZ-DCM. Furthermore, we employed the developer with 3% content of Boc-PZ-DCM to develop the sweat latent fingerprints on different substrates by powder dusting, and collected clear fingerprint patterns, indicating that the developer is universal. In a word, the Boc-PZ-DCM/MMT powder is a promising candidate for LFP developer.
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As one of the typical fluorescent cores, dicyanomethylene-4H-pyran (DCM) derivatives exhibit excellent photophysical and photochemical properties, such as large Stokes shift, excellent light stability, and tunable near-infrared (NIR) emission. The luminescence mechanism of DCM probes mainly depends on the intramolecular charge transfer (ICT). Hence, by regulating the ICT process, the probes can specifically act on the target molecule. Accordingly, a series of NIR DCM probes have been constructed to detect the ions, reactive oxygen species (ROS), and biological macromolecules in cells. However, there is no relevant review to summarize it at present. This minireview mainly summarizes the NIR DCM probes based on ICT effect and their applications in biosensors and biological imaging in recent years. This will be beneficial to innovatively construct new DCM probes and actively promote their application in the future.
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Hen egg white lysozyme (HEWL) is frequently applied as a model protein for research on protein folding, unfolding, and fibrillization identified by featured fluorescent probes. Here, a series of hydrophilic, pH-sensitive tetraarylethene (TAE)-type AIEgens are synthesized via a geminal cross-coupling (GCC) reaction and evaluated for their capabilities of fluorescence sensing and super-resolution localization imaging of HEWL fibrils. With superior optical and sensing properties, the selected TAE-type AIEgen probe is weakly emissive in aqueous media, without dependence on the pH value and buffer concentration, but exhibits "turn-on" fluorescence upon interaction with HEWL amyloid fibrils in a spontaneous and reversible way that just meets the requirement of fluorescence random switching for super-resolution imaging. The selected probe has the strongest fluorescence response to HEWL amyloid fibrils exhibiting a limit of detection of 0.59 nmol/L and enables super-resolution fluorescence imaging of amyloid aggregates with a high resolution of 40 nm.
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Amiloide/química , Microscopía Fluorescente/métodos , Muramidasa/química , Tampones (Química) , Colorantes Fluorescentes , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e HidrofílicasRESUMEN
OBJECTIVE: To evaluate the safety and immunogenicity of the Bilive(TM) combined hepatitis A and hepatitis B vaccine in healthy children. METHODS: A total of 116 healthy children aged 1 - 10 years, who, without history of hepatitis A vaccine vaccination and anti-HAV negative, had completed the full immunization of hepatitis B vaccine were recruited in city of Changzhou in Jiangsu province. The Bilive(TM) combined hepatitis A and hepatitis B vaccine was administered according to a two-dose schedule (0, 6 months). The dosage was 250 U for hepatitis A antigen and 5 microg for hepatitis B surface antigen. The potential adverse effects were observed within 72 hours after vaccination. The serum samples were collected for the testing of anti-HAV and anti-HBs at month 1, 6 and 7 after initial dose. RESULTS: The local and systemic adverse reactions after immunization were slight and temporary. The rates of local and systemic adverse reactions were 12.1% (14/116) and 6.0% (7/116). The sero-conversion rates of HAV were from 92.9% (92/99) to 100.0% (101/101) and the geometric mean titers (GMT) ranged from 47.0 mIU/ml to 2762.3 mIU/ml 1, 6, 7 months after initial dose. The sero-protection rate of HBV was 86.1% (87/101) before vaccination and came up to 100.0% (101/101) one month after initial dose, and the GMTs of HBV were from 894.3 mIU/ml to 3314.3 mIU/ml 1, 6, 7 months after initial dose. CONCLUSION: The Bilive(TM) combined hepatitis A and hepatitis B vaccine has good safety and immunogenicity in healthy children who had preexisting immunity to hepatitis B virus.
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Vacunas contra la Hepatitis A/inmunología , Vacunas contra Hepatitis B/inmunología , Niño , Preescolar , Relación Dosis-Respuesta Inmunológica , Femenino , Vacunas contra la Hepatitis A/efectos adversos , Vacunas contra Hepatitis B/efectos adversos , Humanos , Esquemas de Inmunización , Lactante , Masculino , Vacunas Combinadas/efectos adversos , Vacunas Combinadas/inmunologíaRESUMEN
Photoswitchable fluorescent diarylethenes are promisingly widely applied in the fields of optical memory, all-optical transistors, bioimaging, and super-resolution imaging, and so on. However, they face the problems of fluorescence quenching in an aggregated/solid state, the inadequate fluorescence ON/OFF switching ratio, and the necessity of UV-light irradiation. Herein, we report a novel kind of high-performance diarylethenes with aggregated-induced emission (AIE) by conjugating two diarylethene groups on one AIE-gen (i.e., TPE-2DTE (blue-green fluorescent) and OTPE-2DTE (orange fluorescence)). Their open forms show enhanced fluorescence in the aggregated and solid states. The closed form of TPE-2DTE/OTPE-2DTE was effectively generated upon short-wavelength visible-light (400 nm-450 nm) irradiation, whose fluorescence was dramatically quenched by intra- and inter-molecular energy transfer. Remarkably, 405 nm purple irradiation gives fluorescence ON/OFF ratios of 1196:1 and 1983:1 for TPE-2DTE and OTPE-2DTE, respectively. The reverse process can be accomplished after another longer wavelength irradiation such as 621 nm and shows considerable fatigue resistance. Taking advantage of superior photoswitching properties under visible-light irradiation, TPE-2DTE and OTPE-2DTE were used for super-resolution imaging with a high resolution of sub 50 nm. This work offers guidance to design bright-emitting and high-performance visible-light-controlled diarylethene photoswitches for practical applications.
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Fine particulate matter (PM2.5) has an adverse effect on reproductive function, in particular causing reduced male reproductive function, but relatively few studies have directly targeted its effects on female reproduction. To investigate the effects of PM2.5 exposure on female reproduction, we exposed female mice to PM2.5 by intratracheal instillation for 28 days, and evaluated apoptosis of ovarian granulosa cells and oocytes and the quality embryos after insemination. Our results showed increased numbers of apoptotic granulosa cells and oocytes after exposure to elevated concentrations of PM2.5, which had adverse effects on female fertility via compromising embryo development and quality. We conclude that PM2.5 induced apoptosis of ovarian granulosa cells and oocytes leading to disrupted embryo development and female fertility in mice.