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1.
Gastrointest Endosc ; 96(5): 764-770, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35724696

RESUMEN

BACKGROUND AND AIMS: During endoscopy, droplets with the potential to transmit infectious diseases are known to emanate from a patient's mouth and anus, but they may also be expelled from the biopsy channel of the endoscope. The main goal of our study was to quantify droplets emerging from the biopsy channel during clinical endoscopy. METHODS: A novel light-scattering device was used to measure droplets emanating from the biopsy channel. An endoscopy model was created, and in vitro measurements were carried out during air insufflation, air and water suctioning, and the performance of biopsy sampling. Similar measurements were then made on patients undergoing endoscopy, with all measurements taking place over 2 days to minimize variation. RESULTS: During in vitro testing, no droplets were observed at the biopsy channel during air insufflation or air and water suctioning. In 3 of 5 cases, droplets were observed during biopsy sampling, mostly when the forceps were being removed from the endoscope. In the 22 patients undergoing routine endoscopy, no droplets were observed during air insufflation and water suctioning. Droplets were detected in 1 of 11 patients during air suctioning. In 9 of 18 patients undergoing biopsy sampling and 5 of 6 patients undergoing snare polypectomies, droplets were observed at the biopsy channel, mostly when instruments were being removed from the endoscope. CONCLUSIONS: We found that the biopsy channel may be a source of infectious droplets, especially during the removal of instruments from the biopsy channel. When compared with droplets reported from the mouth and anus, these droplets were larger in size and therefore potentially more infectious.


Asunto(s)
Enfermedades Transmisibles , Endoscopios , Humanos , Endoscopía Gastrointestinal , Biopsia , Endoscopía , Agua
2.
Molecules ; 27(15)2022 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-35956817

RESUMEN

It is inevitable that reclaimed cotton stalks will contain a certain amount of plastic film due to the wide application of plastic mulching during the process of cotton cultivation, and this makes it inappropriate to return it to the field or for it to be processed into silage. In this study, biochars were prepared by the co-pyrolysis of cotton stalk with low-density polyethylene (LDPE) in the proportions of 1:0, 3:1, 2:1, and 1:1 (w/w) at 400 °C, 450 °C, and 500 °C and maintaining them for 1 h. The effects of the co-pyrolysis of cotton stalk with LDPE on the properties of biochars (e.g., pH, yield, elemental analysis, specific surface area, etc.) and the Pb(II) removal capacity were analyzed. Co-pyrolysis cotton stalks with LDPE could delay the decomposition of LDPE but could promote the decomposition of cotton stalk. At 400 °C and 450 °C, the addition of LDPE decreased the H/C ratio, while no significant difference was found between the pristine biochar and the blended biochar pyrolyzed at 500 °C. An FTIR analysis indicated that the surface functional groups of biochar were not affected by the addition of LDPE, except for CH3 and CH2. The results of the SEM showed that LDPE could cover the surface of biochar when pyrolyzed at 400 °C, while many macropores were found in the blended biochar that was pyrolyzed at 450 °C and 500 °C, thus increasing its surface area. The blended biochar that was pyrolyzed at 500 °C was more effective in the removal of Pb(II) than the cotton-stalk-derived biochar, which was dominated by monolayer adsorption with a maximum adsorption capacity of approximately 200 mg·g-1. These results suggested that the co-pyrolysis of cotton stalks and LDPE may be used to produce biochar, which is a cost-effective adsorbent for heavy metal removal from aqueous solutions.


Asunto(s)
Polietileno , Pirólisis , Adsorción , Carbón Orgánico/química , Plomo
3.
J Transl Med ; 19(1): 30, 2021 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-33413461

RESUMEN

BACKGROUND: COVID-19 has caused a global pandemic and the death toll is increasing. However, there is no definitive information regarding the type of clinical specimens that is the best for SARS-CoV-2 detection, the antibody levels in patients with different duration of disease, and the relationship between antibody level and viral load. METHODS: Nasopharyngeal swabs, anal swabs, saliva, blood, and urine specimens were collected from patients with a course of disease ranging from 7 to 69 days. Viral load in different specimen types was measured using droplet digital PCR (ddPCR). Meanwhile, anti-nucleocapsid protein (anti-N) IgM and IgG antibodies and anti-spike protein receptor-binding domain (anti-S-RBD) IgG antibody in all serum samples were tested using ELISA. RESULTS: The positive detection rate in nasopharyngeal swab was the highest (54.05%), followed by anal swab (24.32%), and the positive detection rate in saliva, blood, and urine was 16.22%, 10.81%, and 5.41%, respectively. However, some patients with negative nasopharyngeal swabs had other specimens tested positive. There was no significant correlation between antibody level and days after symptoms onset or viral load. CONCLUSIONS: Other specimens could be positive in patients with negative nasopharyngeal swabs, suggesting that for patients in the recovery period, specimens other than nasopharyngeal swabs should also be tested to avoid false negative results, and anal swabs are recommended. The antibody level had no correlation with days after symptoms onset or the viral load of nasopharyngeal swabs, suggesting that the antibody level may also be affected by other factors.


Asunto(s)
Anticuerpos Antivirales/sangre , COVID-19/inmunología , COVID-19/virología , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificación , Carga Viral , Adulto , Anciano , Anciano de 80 o más Años , Canal Anal/virología , Sangre/virología , COVID-19/epidemiología , Prueba Serológica para COVID-19 , Prueba de COVID-19 , China/epidemiología , Reacciones Falso Negativas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nasofaringe/virología , Pandemias , Saliva/virología , Manejo de Especímenes , Factores de Tiempo , Investigación Biomédica Traslacional , Orina/virología
4.
Glob Chang Biol ; 26(6): 3356-3367, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32281177

RESUMEN

Plastic pollution is a global concern given its prevalence in aquatic and terrestrial ecosystems. Studies have been conducted on the distribution and impact of plastic pollution in marine ecosystems, but little is known on terrestrial ecosystems. Plastic mulch has been widely used to increase crop yields worldwide, yet the impact of plastic residues in cropland soils to soil health and crop production in the long term remained unclear. In this paper, using a global meta-analysis, we found that the use of plastic mulch can indeed increase crop yields on average by 25%-42% in the immediate season due to the increase of soil temperature (+8%) and moisture (+17%). However, the unabated accumulation of film residues in the field negatively impacts its physicochemical properties linked to healthy soil and threatens food production in the long term. It has multiple negative impacts on plant growth including crop yield (at the mean rate of -3% for every additional 100 kg/ha of film residue), plant height (-2%) and root weight (-5%), and soil properties including soil water evaporation capacity (-2%), soil water infiltration rate (-8%), soil organic matter (-0.8%) and soil available phosphorus (-5%) based on meta-regression. Using a nationwide field survey of China, the largest user of plastic mulch worldwide, we found that plastic residue accumulation in cropland soils has reached 550,800 tonnes, with an estimated 6%-10% reduction in cotton yield in some polluted sites based on current level of plastic residue content. Immediate actions should be taken to ensure the recovery of plastic film mulch and limit further increase in film residue loading to maintain the sustainability of these croplands.


Asunto(s)
Agricultura , Plásticos , China , Productos Agrícolas , Ecosistema , Abastecimiento de Alimentos , Suelo
5.
Small ; 14(45): e1803101, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30300473

RESUMEN

Theranostic materials are of great significance to a personalized precise medicine. However, conventional theranostic agents are mainly fabricated by combining presynthesized independent imaging probes and therapeutic agents, suffering from multiple synthesis procedures, poor morphological control, and time/reagent-consuming process. Herein, iodinated polypyrrole (I-PPy) nanoparticles are fabricated via a one-step synthesis strategy combining chemical oxidation and iodination for computed tomography (CT) imaging-guided photothermal therapy. Iodic acid with a high standard electrode potential enables the chemical oxidation polymerization of pyrrole monomers. Meanwhile, the iodination of PPy induced by the corresponding reduction product I2 takes place during the polymerization process to generate I-PPy nanoparticles. The prepared I-PPy nanoparticles possess a uniform size, excellent colloidal stability, intense near-infrared absorption, strong X-ray attenuation ability, and favorable biocompatibility. The as-synthesized I-PPy nanoparticles not only guarantee remarkable contrast-enhanced CT imaging of blood pool and tumors, but also realize effective tumor suppression in vitro and in vivo by I-PPy nanoparticles-mediated CT imaging-guided photothermal therapy. To the best of the authors' knowledge, it is the first time that multifunctional PPy nanoparticles are fabricated through a one-step synthesis process. The proposed strategy opens up a new way for the fabrication of high-performance theranostic agents via a one-step strategy under mild conditions.


Asunto(s)
Nanopartículas/química , Fototerapia/métodos , Polímeros/química , Pirroles/química , Animales , Halogenación , Humanos , Tomografía Computarizada por Rayos X
6.
ACS Nano ; 18(6): 4783-4795, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38301134

RESUMEN

Contrast-enhanced magnetic resonance imaging (CE-MRI) of acute kidney injury (AKI) is severely hindered by the poor targeting capacity and potential toxicity of current contrast agents. Herein, we propose one-step fabrication of a bovine serum albumin@polydopamine@Fe (BSA@PDA@Fe, BPFe) nanoprobe with self-purification capacity for targeted CE-MRI of AKI. BSA endows the BPFe nanoprobe with renal tubule-targeting ability, and PDA is capable of completely inhibiting the intrinsic metal-induced reactive oxygen species (ROS), which are always involved in Fe/Mn-based agents. The as-prepared nanoprobe owns a tiny size of 2.7 nm, excellent solubility, good T1 MRI ability, superior biocompatibility, and powerful antioxidant capacity. In vivo CE-MRI shows that the BPFe nanoprobe can accumulate in the renal cortex due to the reabsorption effect toward the serum albumin. In the AKI model, impaired renal reabsorption function can be effortlessly detected via the diminishment of renal cortical signal enhancement. More importantly, the administration of the BPFe nanoprobe would not aggravate renal damage of AKI due to the outstanding self-purification capacity. Besides, the BPFe nanoprobe is employed for CE-MR angiography to visualize fine vessel structures. This work provides an MRI contrast agent with good biosafety and targeting ability for CE-MRI of kidney diseases.


Asunto(s)
Lesión Renal Aguda , Indoles , Polímeros , Humanos , Medios de Contraste/química , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos
7.
Sci Total Environ ; 942: 173697, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-38851350

RESUMEN

Surfactants as synergistic agents are necessary to improve the stability and utilization of pesticides, while their use is often accompanied by unexpected release into the environment. However, there are no efficient strategies available for screening low-toxicity surfactants, and traditional toxicity studies rely on extensive experimentation which are not predictive. Herein, a commonly used agricultural adjuvant Triton X (TX) series was selected to study the function of amphipathic structure to their toxicity in zebrafish. Molecular dynamics (MD) simulations, transcriptomics, metabolomics and machine learning (ML) were used to study the toxic effects and predict the toxicity of various TX. The results showed that TX with a relatively short hydrophilic chain was highly toxic to zebrafish with LC50 of 1.526 mg/L. However, TX with a longer hydrophilic chain was more likely to damage the heart, liver and gonads of zebrafish through the arachidonic acid metabolic network, suggesting that the effect of surfactants on membrane permeability is the key to determine toxic results. Moreover, biomarkers were screened through machine learning, and other hydrophilic chain lengths were predicted to affect zebrafish heart health potentially. Our study provides an advanced adjuvants screening method to improve the bioavailability of pesticides while reducing environmental impacts.


Asunto(s)
Aprendizaje Automático , Simulación de Dinámica Molecular , Plaguicidas , Pez Cebra , Animales , Plaguicidas/toxicidad , Tensoactivos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Octoxinol/toxicidad
8.
Children (Basel) ; 11(7)2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-39062212

RESUMEN

Artificial intelligence has been applied to medical diagnosis and decision-making but it has not been used for classification of Class III malocclusions in children. OBJECTIVE: This study aims to propose an innovative machine learning (ML)-based diagnostic model for automatically classifies dental, skeletal and functional Class III malocclusions. METHODS: The collected data related to 46 cephalometric feature measurements from 4-14-year-old children (n = 666). The data set was divided into a training set and a test set in a 7:3 ratio. Initially, we employed the Recursive Feature Elimination (RFE) algorithm to filter the 46 input parameters, selecting 14 significant features. Subsequently, we constructed 10 ML models and trained these models using the 14 significant features from the training set through ten-fold cross-validation, and evaluated the models' average accuracy in test set. Finally, we conducted an interpretability analysis of the optimal model using the ML model interpretability tool SHapley Additive exPlanations (SHAP). RESULTS: The top five models ranked by their area under the curve (AUC) values were: GPR (0.879), RBF SVM (0.876), QDA (0.876), Linear SVM (0.875) and L2 logistic (0.869). The DeLong test showed no statistical difference between GPR and the other models (p > 0.05). Therefore GPR was selected as the optimal model. The SHAP feature importance plot revealed that he top five features were SN-GoMe (the ratio of the length of the anterior skull base SN to that of the mandibular base GoMe), U1-NA (maxillary incisor angulation to NA plane), Overjet (the distance between two lines perpendicular to the functional occlusal plane from U1 and L), ANB (the difference between angles SNA and SNB), and AB-NPo (the angle between the AB and N-Pog line). CONCLUSIONS: Our findings suggest that ML models based on cephalometric data could effectively assist dentists to classify dental, functional and skeletal Class III malocclusions in children. In addition, features such as SN_GoMe, U1_NA and Overjet can as important indicators for predicting the severity of Class III malocclusions.

9.
Orphanet J Rare Dis ; 18(1): 371, 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38037133

RESUMEN

BACKGROUND: Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis is a rare, autosomal recessive, skeletal disorder first described in 2018. This syndrome starts with pre- and postnatal developmental delay, and gradually presents with variable facial dysmorphisms, a short stature, amelogenesis imperfecta, and progressive skeletal dysplasia affecting the limbs, joints, hands, feet, and spine. CASE PRESENTATION: We identified a homozygous novel nonsense mutation in exon 1 of SLC10A7 (NM_001300842.2: c.100G > T / p.Gly34*) segregating with the typical disease phenotype in a Han Chinese family. We reviewed the 12-year surgical treatment history with seven interventions on spine. CONCLUSION: To date, only 12 cases of the SLC10A7 mutation have been reported, mainly from consanguineous families. Our patient showed a relatively severe and broad clinical phenotype compared with previously reported cases. In this patient, annual check-ups and timely surgeries led to a good outcome.


Asunto(s)
Amelogénesis Imperfecta , Enanismo , Osteocondrodisplasias , Escoliosis , Humanos , Amelogénesis Imperfecta/genética , Amelogénesis Imperfecta/cirugía , Enanismo/genética , Enanismo/cirugía , Homocigoto , Mutación/genética , Osteocondrodisplasias/genética , Osteocondrodisplasias/cirugía , Linaje , Escoliosis/genética , Escoliosis/cirugía
10.
Diagnostics (Basel) ; 13(10)2023 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-37238203

RESUMEN

Malocclusions are a type of cranio-maxillofacial growth and developmental deformity that occur with high incidence in children. Therefore, a simple and rapid diagnosis of malocclusions would be of great benefit to our future generation. However, the application of deep learning algorithms to the automatic detection of malocclusions in children has not been reported. Therefore, the aim of this study was to develop a deep learning-based method for automatic classification of the sagittal skeletal pattern in children and to validate its performance. This would be the first step in establishing a decision support system for early orthodontic treatment. In this study, four different state-of-the-art (SOTA) models were trained and compared by using 1613 lateral cephalograms, and the best performance model, Densenet-121, was selected was further subsequent validation. Lateral cephalograms and profile photographs were used as the input for the Densenet-121 model, respectively. The models were optimized using transfer learning and data augmentation techniques, and label distribution learning was introduced during model training to address the inevitable label ambiguity between adjacent classes. Five-fold cross-validation was conducted for a comprehensive evaluation of our method. The sensitivity, specificity, and accuracy of the CNN model based on lateral cephalometric radiographs were 83.99, 92.44, and 90.33%, respectively. The accuracy of the model with profile photographs was 83.39%. The accuracy of both CNN models was improved to 91.28 and 83.98%, respectively, while the overfitting decreased after addition of label distribution learning. Previous studies have been based on adult lateral cephalograms. Therefore, our study is novel in using deep learning network architecture with lateral cephalograms and profile photographs obtained from children in order to obtain a high-precision automatic classification of the sagittal skeletal pattern in children.

11.
J Biol Chem ; 285(23): 17614-27, 2010 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-20382739

RESUMEN

Interactions of Bcl-2 family proteins regulate permeability of the mitochondrial outer membrane and apoptosis. In particular, Bax forms an oligomer that permeabilizes the membrane. To map the interface of the Bax oligomer we used Triton X-100 as a membrane surrogate and performed site-specific photocross-linking. Bax-specific adducts were formed through photo-reactive probes at multiple sites that can be grouped into two surfaces. The first surface overlaps with the BH1-3 groove formed by Bcl-2 Homology motif 1, 2, and 3; the second surface is a rear pocket located on the opposite side of the protein from the BH1-3 groove. Further cross-linking experiments using Bax BH3 peptides and mutants demonstrated that the two surfaces interact with their counterparts in neighboring proteins to form two separated interfaces and that interaction at the BH1-3 groove primes the rear pocket for further interaction. Therefore, Bax oligomerization proceeds through a series of interactions that occur at separate, yet allosterically, coupled interfaces.


Asunto(s)
Apoptosis , Proteína X Asociada a bcl-2/metabolismo , Sitio Alostérico , Secuencias de Aminoácidos , Bioquímica/métodos , Reactivos de Enlaces Cruzados/química , Detergentes/farmacología , Humanos , Mutación , Octoxinol/farmacología , Péptidos/química , Plásmidos/metabolismo , Unión Proteica , Estructura Terciaria de Proteína , Proteínas Proto-Oncogénicas c-bcl-2/química
12.
J Biomed Mater Res A ; 109(10): 1955-1966, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34085403

RESUMEN

A main problem in the design of blood-contacting biomaterials has been the deficiency of a systematic understanding of blood-biomaterial interactions and the strategy to modulate blood responses. In this work, different functional groups including carboxyl (COOH), hydroxyl (OH) and zwitterionic sulfobetaine group (⊕N((CH3 )2 )(CH2 )3 SO3-○- , SMDB) were grafted on the poly (butylene terephthalate) (PBT) film to study how the functional groups modulate blood responses and in terms of interaction with the coagulation system, the complement system, and platelets. The results showed protein absorption and platelet adhesion was stronger on the PBT bearing COOH group than PBT films bearing OH and zwitterionic sulfobetaine groups (total protein (µg/cm2 ): 32.92 ± 5.89 vs. 22.02 ± 1.44 vs. 19.09 ± 1.59; platelet adhesion (/mm2 ): 1,626.7 ± 120.1 vs. 1,395.6 ± 363.3 vs. 1,102.2 ± 373.7), which had a rougher and negatively charged surface, and the coagulation system was inhibited by binding fibrinogen (Fg) and coagulation factors. Meanwhile, PBT-PSMDB showed anticoagulant property and induced platelet activation. As a result, complement formation on these two films were less than PBT bearing OH groups by inhibiting the coagulation system (C3a (ng/ml): 3,745.4 ± 143.9 vs. 3,290.9 ± 249.7 vs. 4,887.9 ± 88.9; C5a (ng/ml): 22.1 ± 2.6 vs. 22.3 ± 1.8 vs. 27.9 ± 2.0). On the other hand, PBT bearing OH groups did not facilitate remarkable platelet adhesion and activation, and had no influence on platelet aggregation, hypotonic shock response, and coagulation system. The above results showed that the blood responses were highly interlinked, and could be modulated by grafting with different functional groups on the biomaterial surfaces. These findings may help identify a strategy to design materials with better hemocompatibility for blood contact, filtration, and purification applications.


Asunto(s)
Eritrocitos/efectos de los fármacos , Poliésteres/química , Poliésteres/farmacología , Adsorción , Coagulación Sanguínea/efectos de los fármacos , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Plaquetas/ultraestructura , Activación de Complemento/efectos de los fármacos , Fibrinógeno/metabolismo , Hemólisis/efectos de los fármacos , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Ensayo de Materiales , Espectroscopía de Fotoelectrones , Adhesividad Plaquetaria/efectos de los fármacos , Espectroscopía Infrarroja por Transformada de Fourier , Propiedades de Superficie
13.
J Virol ; 83(21): 10931-40, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19706710

RESUMEN

Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV), a positive-strand RNA virus that belongs to the Arteriviridae family of Nidovirales, has been identified as the causative agent of PRRS. Nsp1alpha is the amino (N)-terminal protein in a polyprotein encoded by the PRRSV genome and is reported to be crucial for subgenomic mRNA synthesis, presumably by serving as a transcription factor. Before functioning in transcription, nsp1alpha proteolytically releases itself from nsp1beta. However, the structural basis for the self-releasing and biological functions of nsp1alpha remains elusive. Here we report the crystal structure of nsp1alpha of PRRSV (strain XH-GD) in its naturally self-processed form. Nsp1alpha contains a ZF domain (which may be required for its biological function), a papain-like cysteine protease (PCP) domain with a zinc ion unexpectedly bound at the active site (which is essential for proteolytic self-release of nsp1alpha), and a carboxyl-terminal extension (which occupies the substrate binding site of the PCP domain). Furthermore, we determined the exact location of the nsp1alpha self-processing site at Cys-Ala-Met180 downward arrowAla-Asp-Val by use of crystallographic data and N-terminal amino acid sequencing. The crystal structure also suggested an in cis self-processing mechanism for nsp1alpha. Furthermore, nsp1alpha appears to have a dimeric architecture both in solution and as a crystal, with a hydrophilic groove on the molecular surface that may be related to nsp1alpha's biological function. Compared with existing structure and function data, our results suggest that PRRSV nsp1alpha functions differently from other reported viral leader proteases, such as that of foot-and-mouth disease.


Asunto(s)
Endopeptidasas/química , Poliproteínas/química , Virus del Síndrome Respiratorio y Reproductivo Porcino/química , Estructura Cuaternaria de Proteína , Estructura Terciaria de Proteína , Proteínas no Estructurales Virales/química , Secuencia de Aminoácidos , Animales , Dominio Catalítico , Cristalografía por Rayos X , Endopeptidasas/genética , Endopeptidasas/metabolismo , Modelos Moleculares , Datos de Secuencia Molecular , Poliproteínas/genética , Poliproteínas/metabolismo , Síndrome Respiratorio y de la Reproducción Porcina/virología , Multimerización de Proteína , Alineación de Secuencia , Porcinos , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismo
14.
Neurol Genet ; 5(6): e375, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31872054

RESUMEN

OBJECTIVE: A 2-stage genome-wide association was conducted to explore the genetic etiology of amyotrophic lateral sclerosis (ALS) in the Chinese Han population. METHODS: Totally, 700 cases and 4,027 controls were genotyped in the discovery stage using Illumina Human660W-Quad BeadChips. Top associated single nucleotide polymorphisms from the discovery stage were then genotyped in an independent cohort with 884 cases and 5,329 controls. Combined analysis was conducted by combining all samples from the 2 stages. RESULTS: Two novel loci, 1p31 and 12p11, showed strong associations with ALS. These novel loci explained 2.2% of overall variance in disease risk. Expression quantitative trait loci searches identified TYW/CRYZ and FGD4 as risk genes at 1p13 and 12p11, respectively. CONCLUSIONS: This study identifies novel susceptibility genes for ALS. Identification of TYW3/CRYZ in the current study supports the notion that insulin resistance may be involved in ALS pathogenesis, whereas FGD4 suggests an association with Charcot-Marie-Tooth disease.

15.
Theranostics ; 8(11): 2939-2953, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29896295

RESUMEN

The simple integration of chemotherapeutic drugs and photosensitizers (PSs) into the same nanocarriers only achieves a combination of chemo-photodynamic therapy but may not confer synergistic effects. The boosted intracellular release of chemotherapeutic drugs during the photodynamic therapy (PDT) process is necessary to achieve a cascade of amplified synergistic therapeutic effects of chemo-photodynamic therapy. Methods: In this study, we explored an innovative hyperbranched polyphosphate (RHPPE) containing a singlet oxygen (SO)-labile crosslinker to boost drug release during the PDT process. The photosensitizer chlorin e6 (Ce6) and doxorubicin (DOX) were simultaneously loaded into RHPPE nanoparticles (denoted as SOHNPCe6/DOX). The therapeutic efficacy of SOHNPCe6/DOX against drug-resistant cancer was evaluated in vitro and in vivo. Results: Under 660-nm light irradiation, SOHNPCe6/DOX can produce SO, which not only induces PDT against cancer but also cleaves the thioketal linkers to destroy the nanoparticles. Subsequently, boosted DOX release can be achieved, activating a chemotherapy cascade to synergistically destroy the remaining tumor cells after the initial round of PDT. Furthermore, SOHNPCe6/DOX also efficiently detected the tumor area by photoacoustic/magnetic resonance bimodal imaging. Under the guidance of bimodal imaging, the laser beam was precisely focused on the tumor areas, and subsequently, SOHNPCe6/DOX realized a cascade of amplified synergistic chemo-photodynamic therapeutic effects. High antitumor efficacy was achieved even in a drug-resistant tumor model. Conclusion: The designed SOHNPCe6/DOX with great biocompatibility is promising for use as a co-delivery carrier for combined chemo-photodynamic therapy, providing an alternative avenue to achieve a cascade of amplified synergistic effects of chemo-photodynamic therapy for cancer treatment.


Asunto(s)
Antibióticos Antineoplásicos/farmacología , Doxorrubicina/farmacología , Neoplasias/tratamiento farmacológico , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Porfirinas/farmacología , Fármacos Sensibilizantes a Radiaciones/farmacología , Antibióticos Antineoplásicos/química , Línea Celular Tumoral , Clorofilidas , Doxorrubicina/química , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Sinergismo Farmacológico , Humanos , Nanopartículas , Fármacos Fotosensibilizantes/química , Polímeros/química , Porfirinas/química , Fármacos Sensibilizantes a Radiaciones/química , Especies Reactivas de Oxígeno/química , Nanomedicina Teranóstica
16.
BMC Struct Biol ; 6: 27, 2006 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-17187687

RESUMEN

BACKGROUND: The protein encoded by the SA1388 gene from Staphylococcus aureus was chosen for structure determination to elucidate its domain organization and confirm our earlier remote homology based prediction that it housed a nitrogen regulatory PII protein-like domain. SA1388 was predicted to contain a central PII-like domain and two flanking regions, which together belong to the NIF3-like protein family. Proteins like SA1388 remain a poorly studied group and their structural characterization could guide future investigations aimed at understanding their function. RESULTS: The structure of SA1388 has been solved to 2.0A resolution by single wavelength anomalous dispersion phasing method using selenium anomalous signals. It reveals a canonical NIF3-like fold containing two domains with a PII-like domain inserted in the middle of the polypeptide. The N and C terminal halves of the NIF3-like domains are involved in dimerization, while the PII domain forms trimeric contacts with symmetry related monomers. Overall, the NIF3-like domains of SA1388 are organized as a hexameric toroid similar to its homologs, E. coli ybgI and the hypothetical protein SP1609 from Streptococcus pneumoniae. The openings on either side of the toroid are partially covered by trimeric "lids" formed by the PII domains. The junction of the two NIF3 domains has two zinc ions bound at what appears to be a histidine rich active site. A well-defined electron density corresponding to an endogenously bound ligand of unknown identity is observed in close proximity to the metal site. CONCLUSION: SA1388 is the third member of the NIF3-like family of proteins to be structurally characterized, the other two also being hypothetical proteins of unknown function. The structure of SA1388 confirms our earlier prediction that the inserted domain that separates the two NIF3 domains adopts a PII-like fold and reveals an overall capped toroidal arrangement for the protein hexamer. The six PII-like domains form two trimeric "lids" that cap the central cavity of the toroid on either side and provide only small openings to allow regulated entry of small molecules into the occluded chamber. The presence of the electron density of the bound ligand may provide important clues on the likely function of NIF3-like proteins.


Asunto(s)
Proteínas Bacterianas/química , Proteínas PII Reguladoras del Nitrógeno/química , Staphylococcus aureus/química , Sitios de Unión , Cristalografía , Dimerización , Proteínas de Escherichia coli/química , Modelos Moleculares , Polímeros/química , Estructura Terciaria de Proteína
17.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 21(2): 200-4, 2004 Apr.
Artículo en Zh | MEDLINE | ID: mdl-15143539

RESUMEN

In this study, the general toxicity tests including acute toxicity test, haemolysis test, MTT assay of Ti-Fe-Mo-Mn-Nb-Zr alloys were carried out. The morphology of these cells was also observed under phase-contrast microscope. By using X-ray photoelectron spectroscopy(XPS), the kind and mol% of element in surface film were studied. The kind and concentration of element in dipping fluid were investigated by ICP atomic emission spectrometry. The results showed the primary component is TiO2 in surface film. The dipping fluid of Ti-Fe-Mo-Mn-Nb-Zr alloys contains Fe 0.2-1.07 mg/l and Mn 0.16-0.5 mg/l; such dental materials are beneficial to health. No cytotoxic effect was disclosed by in vitro and in vivo tests. The level of cytotoxicity was grade 0 and 1; the haemolysis degree was 0.558%-0.642%, i.e. less than 5%. The cells growing in the extract showed normal morphology. These data indicate that Ti-Fe-Mo-Mn-Nb-Zr alloy, as a dental material, has good biocompatibility.


Asunto(s)
Materiales Biocompatibles/toxicidad , Aleaciones Dentales/toxicidad , Titanio/toxicidad , Animales , Materiales Biocompatibles/química , Hierro/toxicidad , Masculino , Manganeso , Ratones , Molibdeno/toxicidad , Niobio/toxicidad , Fragilidad Osmótica , Conejos , Distribución Aleatoria , Espectrometría por Rayos X , Circonio/toxicidad
18.
Shanghai Kou Qiang Yi Xue ; 22(6): 715-7, 2013 Dec.
Artículo en Zh | MEDLINE | ID: mdl-24469142

RESUMEN

PURPOSE: To investigate the reasons why 13 MK1 attachment were re-fabricated and to suggest some improvement methods. METHODS: Mechanics and denture production technology were reviewed in 13 cases with MK1 attachment denture to determine the causes of failure. RESULTS: In some cases, MK1 attachments were poorly designed, while in other cases problems were found during denture design and production process due to limited experiences at the initial stage. MK1 attachments were re-done based on the specific cause and the outcome was good after 1-1.5 years of follow-up. CONCLUSIONS: When using MK1 attachment, prosthodontists should be familiar with the characteristics and indications of MK1 attachment. Meanwhile, we should strengthen doctor-patient communication and follow up patients timely to improve the success rate of MK1 attached denture repair.


Asunto(s)
Diseño de Dentadura , Humanos
19.
Protein Cell ; 4(10): 782-92, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24026848

RESUMEN

Coxsackievirus A16 belongs to the family Picornaviridae, and is a major agent of hand-foot-and-mouth disease that infects mostly children, and to date no vaccines or antiviral therapies are available. 2A protease of enterovirus is a nonstructural protein and possesses both self-cleavage activity and the ability to cleave the eukaryotic translation initiation factor 4G. Here we present the crystal structure of coxsackievirus A16 2A protease, which interestingly forms hexamers in crystal as well as in solution. This structure shows an open conformation, with its active site accessible, ready for substrate binding and cleavage activity. In conjunction with a previously reported "closed" state structure of human rhinovirus 2, we were able to develop a detailed hypothesis for the conformational conversion triggered by two "switcher" residues Glu88 and Tyr89 located within the bll2-cII loop. Substrate recognition assays revealed that amino acid residues P1', P2 and P4 are essential for substrate specificity, which was verified by our substrate binding model. In addition, we compared the in vitro cleavage efficiency of 2A proteases from coxsackievirus A16 and enterovirus 71 upon the same substrates by fluorescence resonance energy transfer (FRET), and observed higher protease activity of enterovirus 71 compared to that of coxsackievirus A16. In conclusion, our study shows an open conformation of coxsackievirus A16 2A protease and the underlying mechanisms for conformational conversion and substrate specificity. These new insights should facilitate the future rational design of efficient 2A protease inhibitors.


Asunto(s)
Cisteína Endopeptidasas/química , Enfermedad de Boca, Mano y Pie/enzimología , Picornaviridae/enzimología , Conformación Proteica , Proteínas Virales/química , Infecciones por Coxsackievirus/virología , Cristalografía por Rayos X , Cisteína Endopeptidasas/genética , Transferencia Resonante de Energía de Fluorescencia , Enfermedad de Boca, Mano y Pie/patología , Enfermedad de Boca, Mano y Pie/virología , Humanos , Picornaviridae/química , Picornaviridae/genética , Relación Estructura-Actividad , Especificidad por Sustrato , Proteínas Virales/genética
20.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 45(1): 16-9, 2010 Jan.
Artículo en Zh | MEDLINE | ID: mdl-20368034

RESUMEN

OBJECTIVE: To investigate the relationship between condyle movement and temporomandibular disorders (TMD) in patients with Class II division 1 malocclusion. METHODS: Twenty patients (from 11 to 12 years old) with Class II division 1 malocclusion before treatment were collected. Computer aided diagnosis axiograph (CADIAX) and magnetic resonance images (MRI) were used to analyze the condyle movement between disc displacement and normal groups. RESULTS: The sensitive values were found in open/close process in patients with disc displacement: Y [Left: (0.32 +/- 0.10) mm, Right: (-0.91 +/- 0.49) mm ], Z [Left: (4.20 +/- 0.70) mm, Right: (3.44 +/- 0.21) mm], sagittal condylar inclination (SCI) [Left: (32.48 +/- 7.70) degrees , Right: (33.47 +/- 12.60) degrees ] and horizontal condylar inclination (TCI) [Left: (-2.60 +/- 2.02) degrees , R: (-9.23 +/- 5.58) degrees ], and those items showed significant difference between two groups. CONCLUSIONS: The side shift of condyle movement in maximum open/close process might be the inducement of disc displacement. It was revealed that the changes in condyle movement could give useful information in early stage of functional treatment.


Asunto(s)
Maloclusión Clase II de Angle/fisiopatología , Cóndilo Mandibular/patología , Movimiento , Disco de la Articulación Temporomandibular/patología , Trastornos de la Articulación Temporomandibular/patología , Niño , Diagnóstico por Computador/instrumentación , Femenino , Humanos , Registro de la Relación Maxilomandibular , Masculino , Maloclusión Clase II de Angle/complicaciones , Cóndilo Mandibular/fisiopatología , Trastornos de la Articulación Temporomandibular/etiología
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