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1.
Mol Cell ; 75(6): 1299-1314.e6, 2019 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-31353207

RESUMEN

MRE11 nuclease forms a trimeric complex (MRN) with RAD50 and NBS1 and plays a central role in preventing genomic instability. When DNA double-strand breaks (DSBs) occur, MRN is quickly recruited to the damage site and initiates DNA end resection; accordingly, MRE11 must be tightly regulated to avoid inefficient repair or nonspecific resection. Here, we show that MRE11 and RAD50 form a complex (MRC) with C1QBP, which stabilizes MRE11/RAD50, while inhibiting MRE11 nuclease activity by preventing its binding to DNA or chromatin. Upon DNA damage, ATM phosphorylates MRE11-S676/S678 to quickly dissociate the MRC complex. Either excess or insufficient C1QBP impedes the recruitment of MRE11 to DSBs and impairs the DNA damage response. C1QBP is highly expressed in breast cancer and positively correlates with MRE11 expression, and the inhibition of C1QBP enhances tumor regression with chemotherapy. By influencing MRE11 at multiple levels, C1QBP is, thus, an important player in the DNA damage response.


Asunto(s)
Ácido Anhídrido Hidrolasas/metabolismo , Proteínas Portadoras/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Unión al ADN/metabolismo , Recombinación Homóloga , Proteína Homóloga de MRE11/metabolismo , Proteínas Mitocondriales/metabolismo , Complejos Multiproteicos/metabolismo , Proteínas Nucleares/metabolismo , Ácido Anhídrido Hidrolasas/genética , Animales , Proteínas Portadoras/genética , Proteínas de Ciclo Celular/genética , Proteínas de Unión al ADN/genética , Células HEK293 , Células HeLa , Humanos , Proteína Homóloga de MRE11/genética , Proteínas Mitocondriales/genética , Complejos Multiproteicos/genética , Proteínas Nucleares/genética , Estabilidad Proteica , Células Sf9 , Spodoptera
2.
Toxicol Appl Pharmacol ; 485: 116876, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38437955

RESUMEN

BACKGROUND: Olanzapine antagonizes dopamine receptors and is prescribed to treat multiple psychiatric conditions. The main side effect of concern for olanzapine is weight gain and metabolic syndrome. Olanzapine induces hyperprolactinemia, however its effect on the mammary gland is poorly documented. METHODS: Rats received olanzapine by gavage or in drinking water at 1, 3, and 6 mg/kg/day for 5-40 days or 100 days, with and without coadministration of bromocriptine or aripiprazole and using once daily or continuous administration strategies. Histomorphology of the mammary gland, concentrations of prolactin, estradiol, progesterone, and olanzapine in serum, mammary gland and adipose tissue, and mRNA and protein expressions of prolactin receptors were analyzed. RESULTS: In adult and prepubescent female rats and male rats, olanzapine induced significant development of mammary glands in dose- and time-dependent manners, with histopathological hyperplasia of mammary ducts and alveoli with lumen dilation and secretion, marked increase of mammary prolactin receptor expression, a marker of breast tissue, and with mild increase of circulating prolactin. This side effect can be reversed after medication withdrawal, but long-term olanzapine treatment for 100 days implicated tumorigenic potentials indicated by usual ductal epithelial hyperplasia. Olanzapine induced mammary development was prevented with the coaddition of the dopamine agonist bromocriptine or partial agonist aripiprazole, or by continuous administration of medication instead of a once daily regimen. CONCLUSIONS: These results shed light on the previously overlooked effect of olanzapine on mammary development and present experimental evidence to support current clinical management strategies of antipsychotic induced side effects in the breast.


Asunto(s)
Antipsicóticos , Aripiprazol , Benzodiazepinas , Bromocriptina , Glándulas Mamarias Animales , Olanzapina , Prolactina , Animales , Olanzapina/toxicidad , Femenino , Glándulas Mamarias Animales/efectos de los fármacos , Glándulas Mamarias Animales/patología , Aripiprazol/toxicidad , Ratas , Prolactina/sangre , Antipsicóticos/toxicidad , Antipsicóticos/efectos adversos , Benzodiazepinas/toxicidad , Masculino , Ratas Sprague-Dawley , Receptores de Prolactina/metabolismo , Estradiol/sangre , Relación Dosis-Respuesta a Droga , Progesterona/sangre , Quinolonas/toxicidad , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Piperazinas/toxicidad
3.
J Am Chem Soc ; 145(31): 17087-17095, 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37523458

RESUMEN

Transition-metal-catalyzed [4 + 1] reaction of dienes and carbon monoxide (CO) is the most straightforward and easily envisioned cyclization for the synthesis of five-membered carbocycles, which are ubiquitously found in natural products and functional molecules. Unfortunately, no test of this reaction was reported, and consequently, chemists do not know whether such kind of reaction works or not. Herein, we report that the [4 + 1] reaction of common dienes and CO cannot work, at least under the catalysis of [Rh(cod)Cl]2. However, using cyclopropyl-capped dienes (also named allylidenecyclopropanes) as substrates, the corresponding [4 + 1] reaction with CO proceeds smoothly in the presence of [Rh(cod)Cl]2. This [4 + 1] reaction, with a broad scope, provides efficient access to five-membered carbocyclic compounds of spiro[2.4]hept-6-en-4-ones. The [4 + 1] cycloadducts can be further transformed into other molecules by using the unique chemistry of cyclopropyl groups present in these molecules. The mechanism of this [4 + 1] reaction has been investigated by quantum chemical calculations, uncovering that cyclopropyl-capped dienes are strained dienes and the oxidative cyclization step in the [4 + 1] catalytic cycle can release this (angular) strain both kinetically and thermodynamically. The strain release in this step then propagates to all followed CO coordination/CO insertion/reductive elimination steps in the [4 + 1] catalytic cycle, helping the realization of this cycloaddition reaction. In contrast, common dienes (including cyclobutyl-capped dienes) do not have such advantages and their [4 + 1] reaction suffers from energy penalty in all steps involved in the [4 + 1] catalytic cycle. The reactivity of ene-allenes for the [4 + 1] reaction with CO is also discussed.

4.
Lipids Health Dis ; 22(1): 222, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38093311

RESUMEN

BACKGROUND: Previous studies demonstrated that mast cells with their degranulated component heparin are the major endogenous factors that stimulate preadipocyte differentiation and promote fascial adipogenesis, and this effect is related to the structure of heparin. Regarding the structural and physiological properties of the negatively charged polymers, hexasulfonated suramin, a centuries-old medicine that is still used for treating African trypanosomiasis and onchocerciasis, is assumed to be a heparin-related analog or heparinoid. This investigation aims to elucidate the influence of suramin on the adipogenesis. METHODS: To assess the influence exerted by suramin on adipogenic differentiation of primary white adipocytes in rats, this exploration was conducted both in vitro and in vivo. Moreover, it was attempted to explore the role played by the sulfonic acid groups present in suramin in mediating this adipogenic process. RESULTS: Suramin demonstrated a dose- and time-dependent propensity to stimulate the adipogenic differentiation of rat preadipocytes isolated from the superficial fascia tissue and from adult adipose tissue. This stimulation was concomitant with a notable upregulation in expression levels of pivotal adipogenic factors as the adipocyte differentiation process unfolded. Intraperitoneal injection of suramin into rats slightly increased adipogenesis in the superficial fascia and in the epididymal and inguinal fat depots. PPADS, NF023, and NF449 are suramin analogs respectively containing 2, 6, and 8 sulfonic acid groups, among which the last two moderately promoted lipid droplet formation and adipocyte differentiation. The number and position of sulfonate groups may be related to the adipogenic effect of suramin. CONCLUSIONS: Suramin emerges as a noteworthy pharmaceutical agent with the unique capability to significantly induce adipocyte differentiation, thereby fostering adipogenesis.


Asunto(s)
Adipogénesis , Suramina , Ratas , Animales , Suramina/farmacología , Antiparasitarios/farmacología , Diferenciación Celular , Adipocitos Blancos , Heparina/farmacología
5.
Br J Cancer ; 126(12): 1663-1675, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35228677

RESUMEN

The binding of T cell immune checkpoint proteins programmed death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) to their ligands allows immune evasion by tumours. The development of therapeutic antibodies, termed checkpoint inhibitors, that bind these molecules or their ligands, has provided a means to release this brake on the host anti-tumour immune response. However, these drugs are costly, are associated with potentially severe side effects, and only benefit a small subset of patients. It is therefore important to identify biomarkers that discriminate between responders and non-responders. This review discusses the determinants for a successful response to antibodies that bind PD-1 or its ligand PD-L1, dividing them into markers found in the tumour biopsy and those in non-tumour samples. It provides an update on the established predictive biomarkers (tumour PD-L1 expression, tumour mismatch repair deficiency and tumour mutational burden) and assesses the evidence for new potential biomarkers.


Asunto(s)
Antígeno B7-H1 , Neoplasias Colorrectales , Animales , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/inmunología , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/inmunología , Humanos , Ligandos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología
6.
Nanotechnology ; 33(21)2022 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-35147519

RESUMEN

In this paper, nanostructured molybdenum selenide (MoSe2) with composited phases are synthesized by hydrothermal method, and the products are modified by metal anoparticles to improve the gas sensing performance. Microstructure characterization shows that few layered 1T/2H-MoSe2nanosheets have been successfully prepared. Both the morphology and component of nanosheets could be tuned by the reaction parameters. It is shown the MoSe2-based nanomaterials have excellent selectivity to nitrogen dioxide (NO2) according to gas sensing properties measurement. The sensitivity of 1T/2H-MoSe2nanosheets modified by Cu nanoparticles is 17.73 (50 ppm NO2) at the optimal operating temperature, which is the highest compared with other samples. The sensors also exhibit rapid response/recovery time and high stability. The sensing mechanism of MoSe2nanosheets toward NO2is investigated based on the first-principles calculation. The results suggest the modification by metal nanoparticles could significantly improve the adsorption energy and charge transfer between gas molecule and MoSe2. This work demonstrates a promising guidance for the design of new NO2gas sensing materials and devices.

7.
Nanotechnology ; 2022 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-35144246

RESUMEN

In this paper, nanostructured Molybdenum Selenide (MoSe2) with composited phases are synthesized by hydrothermal method, and the products are modified by metal anoparticles to improve the gas sensing performance. Microstructure characterization shows that few layered 1T/2H-MoSe2 nanosheets have been successfully prepared. Both the morphology and composition of nanosheets could be tuned by the reaction parameters. It is shown the MoSe2-based nanomaterials have excellent selectivity to Nitrogen dioxide (NO2) according to gas sensing properties measurement. The sensitivity of 1T/2H-MoSe2 nanosheets modified by Cu nanoparticles is 17.73 (50 ppm NO2) at the optimal operating temperature, which is the highest compared with other samples. The sensors also exhibit rapid response/recovery time and high stability. The sensing mechanism of MoSe2 nanosheets toward NO2 is investigated based on the first-principles calculation. The results suggest the modification by metal nanoparticles could significantly improve the adsorption energy and the charge transfer between gas molecule and MoSe2. This work demonstrates a promising guidance for the design of new NO2 gas sensing materials and devices.

8.
Phys Rev Lett ; 126(6): 063201, 2021 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-33635700

RESUMEN

The dissociative above-threshold double ionization (ATDI) of H_{2} in strong laser fields involves the sequential releasing of two electrons at specific instants with the stretching of the molecular bond. By mapping the releasing instants of two electrons to their emission directions in a multicycle polarization-skewed femtosecond laser pulse, we experimentally clock the dissociative ATDI of H_{2} via distinct photon-number-resolved pathways, which are distinguished in the kinetic energy release spectrum of two protons measured in coincidence. The timings of the experimentally resolved dissociative ATDI pathways are in good accordance with the classical predictions. Our results verify the multiphoton scenario of the dissociative ATDI of H_{2} in both time and energy fashion, strengthening the understanding of the strong-field phenomenon and providing a robust tool with a subcycle time resolution to clock abundant ultrafast dynamics of molecules.

9.
Anal Biochem ; 621: 114157, 2021 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-33705723

RESUMEN

Pathogenic Yersinia (Y.) enterocolitica is the primary causative agent of Yersiniosis, with outbreaks in numerous countries around the world, and causes diarrhea and vomiting in animals and humans. Therefore, an instrument-free and convenient nucleic acid visualization method, RPA-SYBR Green I, was established, which combines recombinase polymerase amplification (RPA) with the fluorescent dye SYBR Green I for the detection of the adhesion gene ail in pathogenic Y. enterocolitica. After optimization of a series of conditions such as primer concentration, the detection of pathogenic Y. enterocolitica could be finally completed within about 20 min (from DNA extraction to observation of results) at an isothermal temperature of 39°C. RPA-SYBR Green I had no cross-reactivity with other bacteria and the detection limit was 101 CFU/µL, with sensitivity equal to that of conventional PCR. The method established in this paper and conventional PCR identified a total of 5 spiked samples and 15 meat samples stored in refrigerated, and it was concluded that there was 100% consistency between the two methods. Overall, RPA-SYBR Green I is a visual and facilitate detection assay that can accurately discover pathogenic Y. enterocolitica.


Asunto(s)
Benzotiazoles/química , Diaminas/química , Fluorometría/métodos , Microbiología de Alimentos/métodos , Carne/microbiología , Técnicas de Amplificación de Ácido Nucleico/métodos , Quinolinas/química , Yersinia enterocolitica/genética , Proteínas de la Membrana Bacteriana Externa/genética , ADN Bacteriano/análisis , ADN Bacteriano/genética , Carne/análisis , Recombinasas/metabolismo , Reproducibilidad de los Resultados , Temperatura , Yersinia enterocolitica/aislamiento & purificación
10.
Mol Pharm ; 18(6): 2285-2297, 2021 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-33998814

RESUMEN

Cholecystokinin-2 receptor (CCK2R) has been proven to be a specific biomarker for colorectal malignancies. Immunotoxins are a valuable class of immunotherapy agents consisting of a targeting element and a bacterial or plant toxin. Previous work demonstrated that targeting CCK2R is a good therapeutic strategy for the treatment of colorectal cancer (CRC). In the present study, we developed a new version of CCK2R-targeting immunotoxin GD9P using a targeted peptide, GD9, as the binding motif and a truncated Pseudomonas exotoxin A (PE38) as the cytokiller. BALB/c nude mice were treated with different doses of GD9P, and pharmacodynamics, pharmacokinetic, and toxicological data were obtained throughout this study. Compared to the parental immunotoxin rCCK8PE38, GD9P exhibited about 1.5-fold yield, higher fluorescence intensity, and increased antitumor activity against human CRC in vitro and in vivo. The IC50 values of GD9P in vitro ranged from 1.61 to 4.55 nM. Pharmacokinetic studies were conducted in mice with a T1/2 of 69.315 min. When tumor-bearing nude mice were treated with GD9P at doses ≥2 mg/kg for five doses, a rapid shrinkage in tumor volume and, in some cases, complete remission was observed. A preliminary safety evaluation demonstrated a good safety profile of GD9P as a Pseudomonas exotoxin A-based immunotherapy. The therapy in combination with oxaliplatin can increase the antitumor efficacy and reduce the toxic side effects caused by chemotherapy. In conclusion, the data support the use of GD9P as a promising immunotherapy targeting CCK2R-expressing colorectal malignancies.


Asunto(s)
ADP Ribosa Transferasas/farmacología , Antineoplásicos/farmacología , Toxinas Bacterianas/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Exotoxinas/farmacología , Receptor de Colecistoquinina B/antagonistas & inhibidores , Proteínas Recombinantes de Fusión/farmacología , Factores de Virulencia/farmacología , ADP Ribosa Transferasas/genética , ADP Ribosa Transferasas/uso terapéutico , Animales , Antineoplásicos/uso terapéutico , Toxinas Bacterianas/genética , Toxinas Bacterianas/uso terapéutico , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Exotoxinas/genética , Exotoxinas/uso terapéutico , Humanos , Ratones , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/uso terapéutico , Distribución Tisular , Pruebas de Toxicidad Aguda , Factores de Virulencia/genética , Factores de Virulencia/uso terapéutico , Ensayos Antitumor por Modelo de Xenoinjerto , Exotoxina A de Pseudomonas aeruginosa
11.
Proc Natl Acad Sci U S A ; 115(9): 2049-2053, 2018 02 27.
Artículo en Inglés | MEDLINE | ID: mdl-29440495

RESUMEN

Electrons bound to atoms or molecules can simultaneously absorb multiple photons via the above-threshold ionization featured with discrete peaks in the photoelectron spectrum on account of the quantized nature of the light energy. Analogously, the above-threshold dissociation of molecules has been proposed to address the multiple-photon energy deposition in the nuclei of molecules. In this case, nuclear energy spectra consisting of photon-energy spaced peaks exceeding the binding energy of the molecular bond are predicted. Although the observation of such phenomena is difficult, this scenario is nevertheless logical and is based on the fundamental laws. Here, we report conclusive experimental observation of high-order above-threshold dissociation of H2 in strong laser fields where the tunneling-ionized electron transfers the absorbed multiphoton energy, which is above the ionization threshold to the nuclei via the field-driven inelastic rescattering. Our results provide an unambiguous evidence that the electron and nuclei of a molecule as a whole absorb multiple photons, and thus above-threshold ionization and above-threshold dissociation must appear simultaneously, which is the cornerstone of the nowadays strong-field molecular physics.

12.
BMC Genomics ; 21(1): 577, 2020 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-32831009

RESUMEN

BACKGROUND: Drought is one of the most adverse environmental factors limiting crop productions and it is important to identify key genetic determinants for food safety. Calcium-dependent protein kinases (CPKs) are known to be involved in plant growth, development, and environmental stresses. However, biological functions and regulatory mechanisms of many plant CPKs have not been explored. In our previous study, abundance of the wheat CPK34 (TaCPK34) protein was remarkably upregulated in wheat plants suffering from drought stress, inferring that it could be involved in this stress. Therefore, here we further detected its function and mechanism in response to drought stress. RESULTS: Transcripts of the TaCPK34 gene were significantly induced after PEG-stimulated water deficiency (20% PEG6000) or 100 µM abscisic acid (ABA) treatments. The TaCPK34 gene was transiently silenced in wheat genome by using barley stripe mosaic virus-induced silencing (BSMV-VIGS) method. After 14 days of drought stress, the transiently TaCPK34-silenced wheat seedlings showed more sensitivity compared with control, and the plant biomasses and relative water contents significantly decreased, whereas soluble sugar and MDA contents increased. The iTRAQ-based quantitative proteomics was employed to measure the protein expression profiles in leaves of the transiently TaCPK34-silenced wheat plants after drought stress. There were 6103 proteins identified, of these, 51 proteins exhibited significantly altered abundance, they were involved in diverse function. And sequence analysis on the promoters of genes, which encoded the above identified proteins, indicated that some promoters harbored some ABA-responsive elements. We determined the interactions between TaCPK34 and three identified proteins by using bimolecular fluorescent complementation (BiFC) method and our data indicated that TaCPK34directly interacted with the glutathione S-transferase 1 and prx113, respectively. CONCLUSIONS: Our study suggested that the TaCPK34 gene played positive roles in wheat response to drought stress through directly or indirectly regulating the expression of ABA-dependent manner genes, which were encoding identified proteins from iTRAQ-based quantitative proteomics. And it could be used as one potential gene to develop crop cultivars with improved drought tolerance.


Asunto(s)
Sequías , Triticum , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estrés Fisiológico/genética , Triticum/genética , Triticum/metabolismo
13.
Opt Lett ; 45(24): 6591-6594, 2020 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-33325847

RESUMEN

Optical ionization of N2 and subsequent population redistribution among the ground and excited states of N2+ in an intense laser field are commonly accepted to be fundamentally responsible for the generation of N2+ lasing. By finely controlling this two-step process, the optimization of N2+ lasing is possibly achieved. Here, we design a waveform-controlled polarization-skewed (PS) pumping pulse, in which the leading and falling edges are orthogonally polarized, and their relative field strength and phase can be well controlled. We demonstrate that precise manipulation of the N2+ lasing at 391 nm and 428 nm emissions can be achieved by modulating both the relative phase and amplitudes of the two orthogonally polarized components of the pumping PS pulse. We find that the optimization of N2+ lasing depends not only on the competitive balance between the ionization and post-ionization coupling that varies in different pumping energies but also on the phase with the maximum intensity appearing at the phase of nπ. Orders of magnitude enhancement in the N2+ lasing intensity is observed as the phase changes from (n+1/2)π to nπ. The PS pulse with a controllable spatiotemporal waveform provides us a robust and straightforward tool to efficiently enhance the N2+ lasing emission.

14.
Phys Rev Lett ; 125(5): 053201, 2020 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-32794853

RESUMEN

A fine manipulation of population transfer among molecular quantum levels is a key technology for control of molecular processes. When a light field intensity is increased to the TW-PW cm^{-2} level, it becomes possible to transfer a population to specific excited levels through nonlinear light-molecule interaction, but it has been a challenge to control the extent of the population transfer. We deplete the population in the X^{2}Σ_{g}^{+}(v=0) state of N_{2}^{+} almost completely by focusing a dual-color (800 nm and 1.6 µm) intense femtosecond laser pulse in a nitrogen gas, and make the intensity of N_{2}^{+} lasing at 391 nm enhanced by 5-6 orders of magnitude. By solving a time-dependent Schrödinger equation describing the population transfer among the three lowest electronic states of N_{2}^{+}, we reveal that the X^{2}Σ_{g}^{+}(v=0) population is depleted by the vibrational Raman excitation followed by the electronic excitation A^{2}Π_{u}(v=2,3,4)←X^{2}Σ_{g}^{+}(v=1)←X^{2}Σ_{g}^{+}(v=0), resulting in the excessive population inversion between the B^{2}Σ_{u}^{+}(v=0) and X^{2}Σ_{g}^{+}(v=0) states. Our results offer a promising route to efficient population transfer among vibrational and electronic levels of molecules by a precisely designed intense laser field.

15.
Retina ; 40(12): 2357-2365, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32106157

RESUMEN

PURPOSE: To determine the feasibility of ultra-wide-field imaging and ultra-wide-field intravenous fundus fluorescein angiography (UWF-IV-FFA) in infants with retinopathy of prematurity (ROP) using Optos 200Tx. METHODS: We performed Optos 200Tx capturing on 32 premature infants (14 females) and UWF-IV-FFA with Optos 200Tx on 12 of the 32 infants between April 2017 and July 2018 at the affiliated eye hospital of Wenzhou Medical University and analyzed their fundus images. RESULTS: Ultra-wide-field color images were acquired from 32 infants (64 eyes). UWF-IV-FFA was performed successfully in 12 premature infants (24 eyes). No adverse events were observed. The ultra-wide-field Optos 200Tx color images and UWF-IV-FFA images revealed Stages 1, 2, and 3 ROP and aggressive posterior ROP. CONCLUSION: Ultra-wide-field imaging and intravenous fundus fluorescein angiography using Optos 200Tx are feasible in infants with ROP, which have the potential to screen, diagnose, and follow-up for ROP.


Asunto(s)
Angiografía con Fluoresceína , Fluoresceína/administración & dosificación , Colorantes Fluorescentes/administración & dosificación , Retinopatía de la Prematuridad/diagnóstico , Peso al Nacer , Diagnóstico por Imagen , Estudios de Factibilidad , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Inyecciones Intravenosas , Masculino , Oftalmoscopía
16.
Chem Pharm Bull (Tokyo) ; 68(11): 1061-1068, 2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-32893223

RESUMEN

Ceftiofur (CEF) is a third-generation and the first animal-specific cephalosporin that is widely used in animal husbandry. As a heat-labile antibiotic, the cytotoxicity of CEF after thermal treatment has been reported. This study seeks to investigate the potential toxicity of thermally treated CEF (TTC) in vivo based on acute oral toxicity studies and acute intraperitoneal studies in mice. Our data indicated that TTC exhibited significant increased toxicity in mice compared with CEF. TTC resulted in weight gain, hypercholesterolemia, hepatocyte steatosis and hepatocyte mitochondrial damage, and downregulated ß-oxidation-related genes in mice in acute oral toxicity studies. In addition, TTC caused acute pulmonary congestion, increased levels of reactive oxygen species (ROS), prolonged coagulation time, and even death in mice in acute intraperitoneal toxicity studies. Our data showed that thermal treatment enhanced the toxicity of CEF in vivo. Lung and liver are the main target organs in the pathological damage process mediated by TTC. These findings suggested that residual CEF in animal-derived food may represent a potential food safety risk and pose a potential threat to human health.


Asunto(s)
Antibacterianos/toxicidad , Cefalosporinas/toxicidad , Hígado/efectos de los fármacos , Pulmón/efectos de los fármacos , Temperatura , Administración Oral , Animales , Antibacterianos/administración & dosificación , Coagulación Sanguínea/efectos de los fármacos , Cefalosporinas/administración & dosificación , Relación Dosis-Respuesta a Droga , Inyecciones Intraperitoneales , Hígado/metabolismo , Hígado/patología , Pulmón/metabolismo , Pulmón/patología , Ratones , Ratones Endogámicos ICR , Tamaño de los Órganos/efectos de los fármacos , Especies Reactivas de Oxígeno/análisis
17.
Chin J Cancer Res ; 32(2): 175-185, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32410795

RESUMEN

OBJECTIVE: To evaluate the human epidermal growth factor receptor 2 (HER2) status in patients with breast cancer using multidetector computed tomography (MDCT)-based handcrafted and deep radiomics features. METHODS: This retrospective study enrolled 339 female patients (primary cohort, n=177; validation cohort, n=162) with pathologically confirmed invasive breast cancer. Handcrafted and deep radiomics features were extracted from the MDCT images during the arterial phase. After the feature selection procedures, handcrafted and deep radiomics signatures and the combined model were built using multivariate logistic regression analysis. Performance was assessed by measures of discrimination, calibration, and clinical usefulness in the primary cohort and validated in the validation cohort. RESULTS: The handcrafted radiomics signature had a discriminative ability with a C-index of 0.739 [95% confidence interval (95% CI): 0.661-0.818] in the primary cohort and 0.695 (95% CI: 0.609-0.781) in the validation cohort. The deep radiomics signature also had a discriminative ability with a C-index of 0.760 (95% CI: 0.690-0.831) in the primary cohort and 0.777 (95% CI: 0.696-0.857) in the validation cohort. The combined model, which incorporated both the handcrafted and deep radiomics signatures, showed good discriminative ability with a C-index of 0.829 (95% CI: 0.767-0.890) in the primary cohort and 0.809 (95% CI: 0.740-0.879) in the validation cohort. CONCLUSIONS: Handcrafted and deep radiomics features from MDCT images were associated with HER2 status in patients with breast cancer. Thus, these features could provide complementary aid for the radiological evaluation of HER2 status in breast cancer.

18.
J Am Chem Soc ; 141(14): 5640-5644, 2019 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-30912936

RESUMEN

Sodium superionic conductors are keys to develop high safety and low cost all-solid-state sodium batteries. Among developed sodium ionic conductors, antiperovskite-type ionic conductors have attracted vast interest due to their high structural tolerance and good formability. Herein, we successfully synthesize Na3OBH4 with cubic antiperovskite structure by solid-state reaction from Na2O and NaBH4. Na3OBH4 exhibits ionic conductivity of 4.4 × 10-3 S cm-1 at room temperature (1.1 × 10-2 S cm-1 at 328 K) and activation energy of 0.25 eV. The ionic conductivity is 4 orders of magnitude higher than the existing antiperovskite Na3OX (X = Cl, Br, I). It is shown that such enhancement is not only due to the specific cubic antiperovskite structure of Na3OBH4 but also because of the rotation of BH4 cluster anion. This work deepens the understanding of the antiperovskite structure and the role of cluster anions for superionic conduction.

19.
Phys Rev Lett ; 123(23): 233202, 2019 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-31868470

RESUMEN

We experimentally observe the bond stretching time of one-photon and net-two-photon dissociation pathways of singly ionized H_{2} molecules driven by a polarization-skewed femtosecond laser pulse. By measuring the angular distributions of the ejected photoelectron and nuclear fragments in coincidence, the cycle-changing polarization of the laser field enables us to clock the photon-ionization starting time and photon-dissociation stopping time, analogous to a stopwatch. After the single ionization of H_{2}, our results show that the produced H_{2}^{+} takes almost the same time in the one-photon and net-two-photon dissociation pathways to stretch to the internuclear distance of the one-photon coupled dipole-transition between the ground and excited electronic states. The spatiotemporal mapping character of the polarization-skewed laser field provides us a straightforward route to clock the ultrafast dynamics of molecules with sub-optical-cycle time resolution.

20.
Sheng Li Xue Bao ; 71(4): 562-574, 2019 Aug 25.
Artículo en Zh | MEDLINE | ID: mdl-31440753

RESUMEN

The influence of reward on behavior is one of the hottest research subjects in psychological research. Reward-induced motivation promotes the performance of the participants. In the field of emotional processing, the reward can influence the individual's processing of emotional information, but previous studies have not directly discussed the effect of reward on emotional regulation. The present study focused on whether emotional regulation ability would be improved under the reward condition. Experiment 1 and 2 investigated the effect of reward on negative emotional down-regulation and positive emotional up-regulation respectively. In experiment 1, monetary reward stimulation was introduced on the basis of the classic emotion regulation paradigm, and the subjects were asked to regulate their negative emotion under the condition of reward or non-reward, and evaluate their current affective state subsequently. Similar to experiment 1, experiment 2 required subjects to up-regulate positive emotions under the condition of reward or non-reward. The results of experiment 1 showed that under the reward condition, the negative emotional regulation effect was significantly higher than that under the non-reward condition (P < 0.05). Experiment 2 also showed that compared to non-reward condition, the positive emotion regulation effect was significantly increased under the reward condition (P < 0.05). These results suggested that compared to non-reward condition, participants can regulate their emotion better under the condition of the reward. It is worth noting that the results of Experiment 1 and 2 may be caused by the incentive motivation induced by monetary stimulus, or the positive emotion caused by positive value of money information. Therefore, we carried out experiment 3 and 4 to explore whether the positive emotions induced by money itself can influence the emotional regulation of individuals. In experiment 3, the money pictures were used to induce the positive emotions of subjects, and the subjects were asked to regulate their negative emotion after the presence of money pictures or non-monetary picture, and evaluate their current affective state subsequently. Similarly, experiment 4 required subjects to regulate their positive emotion after the presence of money pictures. The results of experiment 3 and 4 showed that there was no significant difference in the subjects' scores of emotional pleasantness after the presence of money pictures or non-monetary picture (P < 0.05). The results of experiment 3 and 4 excluded the possibility that the positive emotions induced by simple money stimulus pictures could improve individual's emotional regulation ability. To sum up, the improvement of individual's emotional regulation ability was indeed driven by reward motivation in this study, that is, the motivation induced by reward can effectively promote individual's emotional regulation ability.


Asunto(s)
Emociones , Motivación , Recompensa , Humanos
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