Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 243
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Cell ; 186(9): 1912-1929.e18, 2023 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-37044097

RESUMEN

The spectrin-based membrane skeleton is a ubiquitous membrane-associated two-dimensional cytoskeleton underneath the lipid membrane of metazoan cells. Mutations of skeleton proteins impair the mechanical strength and functions of the membrane, leading to several different types of human diseases. Here, we report the cryo-EM structures of the native spectrin-actin junctional complex (from porcine erythrocytes), which is a specialized short F-actin acting as the central organizational unit of the membrane skeleton. While an α-/ß-adducin hetero-tetramer binds to the barbed end of F-actin as a flexible cap, tropomodulin and SH3BGRL2 together create an absolute cap at the pointed end. The junctional complex is strengthened by ring-like structures of dematin in the middle actin layers and by patterned periodic interactions with tropomyosin over its entire length. This work serves as a structural framework for understanding the assembly and dynamics of membrane skeleton and offers insights into mechanisms of various ubiquitous F-actin-binding factors in other F-actin systems.


Asunto(s)
Citoesqueleto , Eritrocitos , Animales , Humanos , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Citoesqueleto/metabolismo , Eritrocitos/citología , Eritrocitos/metabolismo , Espectrina/análisis , Espectrina/metabolismo , Porcinos
2.
Cell ; 184(7): 1865-1883.e20, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33636127

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding of the RNA virus and its interactions with host proteins could improve therapeutic interventions for COVID-19. By using icSHAPE, we determined the structural landscape of SARS-CoV-2 RNA in infected human cells and from refolded RNAs, as well as the regulatory untranslated regions of SARS-CoV-2 and six other coronaviruses. We validated several structural elements predicted in silico and discovered structural features that affect the translation and abundance of subgenomic viral RNAs in cells. The structural data informed a deep-learning tool to predict 42 host proteins that bind to SARS-CoV-2 RNA. Strikingly, antisense oligonucleotides targeting the structural elements and FDA-approved drugs inhibiting the SARS-CoV-2 RNA binding proteins dramatically reduced SARS-CoV-2 infection in cells derived from human liver and lung tumors. Our findings thus shed light on coronavirus and reveal multiple candidate therapeutics for COVID-19 treatment.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Reposicionamiento de Medicamentos , ARN Viral , Proteínas de Unión al ARN/antagonistas & inhibidores , SARS-CoV-2 , Animales , Línea Celular , Chlorocebus aethiops , Aprendizaje Profundo , Humanos , Conformación de Ácido Nucleico , ARN Viral/química , Proteínas de Unión al ARN/metabolismo , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/genética
3.
Proc Natl Acad Sci U S A ; 121(5): e2309384121, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38252835

RESUMEN

High-quality specimen preparation plays a crucial role in cryo-electron microscopy (cryo-EM) structural analysis. In this study, we have developed a reliable and convenient technique called the graphene sandwich method for preparing cryo-EM specimens. This method involves using two layers of graphene films that enclose macromolecules on both sides, allowing for an appropriate ice thickness for cryo-EM analysis. The graphene sandwich helps to mitigate beam-induced charging effect and reduce particle motion compared to specimens prepared using the traditional method with graphene support on only one side, therefore improving the cryo-EM data quality. These advancements may open new opportunities to expand the use of graphene in the field of biological electron microscopy.


Asunto(s)
Grafito , Microscopía por Crioelectrón , Exactitud de los Datos , Movimiento (Física)
4.
Nucleic Acids Res ; 51(W1): W468-W477, 2023 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-37140045

RESUMEN

Fundamental to post-transcriptional regulation, the in vivo binding of RNA binding proteins (RBPs) on their RNA targets heavily depends on RNA structures. To date, most methods for RBP-RNA interaction prediction are based on RNA structures predicted from sequences, which do not consider the various intracellular environments and thus cannot predict cell type-specific RBP-RNA interactions. Here, we present a web server PrismNet that uses a deep learning tool to integrate in vivo RNA secondary structures measured by icSHAPE experiments with RBP binding site information from UV cross-linking and immunoprecipitation in the same cell lines to predict cell type-specific RBP-RNA interactions. Taking an RBP and an RNA region with sequential and structural information as input ('Sequence & Structure' mode), PrismNet outputs the binding probability of the RBP and this RNA region, together with a saliency map and a sequence-structure integrative motif. The web server is freely available at http://prismnetweb.zhanglab.net.


Asunto(s)
Proteínas de Unión al ARN , ARN , ARN/química , Proteínas de Unión al ARN/metabolismo , Sitios de Unión , Regulación de la Expresión Génica
5.
Small ; 20(25): e2309276, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38247194

RESUMEN

Macrophage dysfunction is one of the primary factors leading to the delayed healing of diabetic wounds. Hypoxic bone marrow mesenchymal stem cells-derived exosomes (hyBMSC-Exos) have been shown to play an active role in regulating cellular function through the carried microRNAs. However, the administration of hyBMSC-Exos alone in diabetic wounds usually brings little effect, because the exosomes are inherently unstable and have a short retention time at the wounds. In this study, a multifunctional hydrogel based on gallic acid (GA) conjugated chitosan (Chi-GA) and partially oxidized hyaluronic acid (OHA) is prepared for sustained release of hyBMSC-Exos. The hydrogel not only exhibits needs-satisfying physicochemical properties, but also displays outstanding biological performances such as low hemolysis rate, strong antibacterial capacity, great antioxidant ability, and excellent biocompatibility. It has the ability to boost the stability of hyBMSC-Exos, leading to a continuous and gradual release of the exosomes at wound locations, ultimately enhancing the exosomes' uptake efficiency by target cells. Most importantly, hyBMSC-Exos loaded hydrogel shows an excellent ability to promote diabetic wound healing by regulating macrophage polarization toward M2 phenotype. This may be because exosomal miR-4645-5p and antioxidant property of the hydrogel synergistically inhibit SREBP2 activity in macrophages. This study presents a productive approach for managing diabetic wounds.


Asunto(s)
Complicaciones de la Diabetes , Exosomas , Hidrogeles , Células Madre Mesenquimatosas , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Hidrogeles/uso terapéutico , Exosomas/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Complicaciones de la Diabetes/tratamiento farmacológico , Complicaciones de la Diabetes/patología , Piel/efectos de los fármacos , Piel/lesiones , Humanos , Supervivencia Celular/efectos de los fármacos , Bacterias/efectos de los fármacos
6.
Appl Environ Microbiol ; 90(3): e0211023, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38391210

RESUMEN

Ultraviolet (UV) A radiation (315-400 nm) is the predominant component of solar UV radiation that reaches the Earth's surface. However, the underlying mechanisms of the positive effects of UV-A on photosynthetic organisms have not yet been elucidated. In this study, we investigated the effects of UV-A radiation on the growth, photosynthetic ability, and metabolome of the edible cyanobacterium Nostoc sphaeroides. Exposures to 5-15 W m-2 (15-46 µmol photons m-2 s-1) UV-A and 4.35 W m-2 (20 µmol photons m-2 s-1) visible light for 16 days significantly increased the growth rate and biomass production of N. sphaeroides cells by 18%-30% and 15%-56%, respectively, compared to the non-UV-A-acclimated cells. Additionally, the UV-A-acclimated cells exhibited a 1.8-fold increase in the cellular nicotinamide adenine dinucleotide phosphate (NADP) pool with an increase in photosynthetic capacity (58%), photosynthetic efficiency (24%), QA re-oxidation, photosystem I abundance, and cyclic electron flow (87%), which further led to an increase in light-induced NADPH generation (31%) and ATP content (83%). Moreover, the UV-A-acclimated cells showed a 2.3-fold increase in ribulose-1,5-bisphosphate carboxylase/oxygenase activity, indicating an increase in their carbon-fixing capacity. Gas chromatography-mass spectrometry-based metabolomics further revealed that UV-A radiation upregulated the energy-storing carbon metabolism, as evidenced by the enhanced accumulation of sugars, fatty acids, and citrate in the UV-A-acclimated cells. Therefore, our results demonstrate that UV-A radiation enhances energy flow and carbon assimilation in the cyanobacterium N. sphaeroides.IMPORTANCEUltraviolet (UV) radiation exerts harmful effects on photo-autotrophs; however, several studies demonstrated the positive effects of UV radiation, especially UV-A radiation (315-400 nm), on primary productivity. Therefore, understanding the underlying mechanisms associated with the promotive effects of UV-A radiation on primary productivity can facilitate the application of UV-A for CO2 sequestration and lead to the advancement of photobiological sciences. In this study, we used the cyanobacterium Nostoc sphaeroides, which has an over 1,700-year history of human use as food and medicine, to explore its photosynthetic acclimation response to UV-A radiation. As per our knowledge, this is the first study to demonstrate that UV-A radiation increases the biomass yield of N. sphaeroides by enhancing energy flow and carbon assimilation. Our findings provide novel insights into UV-A-mediated photosynthetic acclimation and provide a scientific basis for the application of UV-A radiation for optimizing light absorption capacity and enhancing CO2 sequestration in the frame of a future CO2 neutral, circular, and sustainable bioeconomy.


Asunto(s)
Nostoc , Rayos Ultravioleta , Humanos , Biomasa , Carbono/metabolismo , Dióxido de Carbono/metabolismo , Nostoc/metabolismo , Fotosíntesis/fisiología
7.
Virol J ; 21(1): 128, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38840203

RESUMEN

The envelope (E) protein of the Japanese encephalitis virus (JEV) is a key protein for virus infection and adsorption of host cells, which determines the virulence of the virus and regulates the intensity of inflammatory response. The mutation of multiple aa residues in the E protein plays a critical role in the attenuated strain of JEV. This study demonstrated that the Asp to Gly, Ser, and His mutation of the E389 site, respectively, the replication ability of the viruses in cells was significantly reduced, and the viral neuroinvasiveness was attenuated to different degrees. Among them, the mutation at E389 site enhanced the E protein flexibility contributed to the attenuation of neuroinvasiveness. In contrast, less flexibility of E protein enhanced the neuroinvasiveness of the strain. Our results indicate that the mechanism of attenuation of E389 aa mutation attenuates neuroinvasiveness is related to increased flexibility of the E protein. In addition, the increased flexibility of E protein enhanced the viral sensitivity to heparin inhibition in vitro, which may lead to a decrease in the viral load entering brain. These results suggest that E389 residue is a potential site affecting JEV virulence, and the flexibility of the E protein of aa at this site plays an important role in the determination of neuroinvasiveness.


Asunto(s)
Virus de la Encefalitis Japonesa (Especie) , Proteínas del Envoltorio Viral , Virus de la Encefalitis Japonesa (Especie)/genética , Virus de la Encefalitis Japonesa (Especie)/fisiología , Virus de la Encefalitis Japonesa (Especie)/efectos de los fármacos , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/metabolismo , Proteínas del Envoltorio Viral/química , Animales , Línea Celular , Virulencia , Replicación Viral , Encefalitis Japonesa/virología , Humanos , Heparina/farmacología , Sustitución de Aminoácidos , Mutación Missense , Ratones , Mutación , Factores de Virulencia/genética , Glicoproteínas de Membrana
8.
Virus Genes ; 60(1): 9-17, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37938470

RESUMEN

Most wild strains of Japanese encephalitis virus (JEV) produce NS1' protein, which plays an important role in viral infection and immune escape. The G66A nucleotide mutation in NS2A gene of the wild strain SA14 prevented the ribosomal frameshift that prevented the production of NS1' protein, thus reduced the virulence. In this study, the 66th nucleotide of the NS2A gene of SA14 was mutated into A, U or C, respectively. Both the G66U and G66C mutations cause the E22D mutation of the NS2A protein. Subsequently, the expression of NS1' protein, plaque size, replication ability, and virulence to mice of the three mutant strains were examined. The results showed that the three mutant viruses could not express NS1' protein, and their proliferation ability in nerve cells and virulence to mice were significantly reduced. In addition, the SA14(G66C) was less virulent than the other two mutated viruses. Our results indicate that only when G is the 66th nucleotide of NS2A, the JEV can produce NS1' protein, which affects the virulence.


Asunto(s)
Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Animales , Ratones , Virus de la Encefalitis Japonesa (Especie)/genética , Nucleótidos/metabolismo , Virulencia/genética , Línea Celular , Proteínas no Estructurales Virales/metabolismo , Proliferación Celular
9.
J Environ Manage ; 360: 121135, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38761623

RESUMEN

Resilience assessment for urban drainage systems is a fundamental aspect of building resilient cities. Recently, some scholars have proposed the Global Resilience Analysis (GRA) method, which assesses resilience based on the functional performance of different system failure scenarios. Compared to traditional system dynamics methods, the GRA method considers the impact of internal structural failure on resilience but requires a large amount of computation. This research proposed an improved GRA method to enhance computational efficiency and practicality by reducing the number of system scenario simulations. Firstly, a hydrodynamic model of the drainage network of Haidian Island has been constructed using the Storm Water Management Model (SWMM) and Python. Secondly, the GRA method was improved using cluster analysis and convergence analysis to reduce the simulation scenarios. Thirdly, a resilience assessment index was established through system function functions, and two types of resilience enhancement measures, centralized and distributed, were proposed. The results show: (i) resilience assessment increases the computational efficiency by 25% compared to the traditional GRA method; (ii) the resilience index of the existing drainage network within Haidian Island is less than the design value (0.7) in all failure scenarios, indicating a lower level of recovery capability; (iii) compared to the centralized strategy, which is only effective when the system failure level is less than 9%, the distributed strategy enhances the resilience of the urban drainage system at a higher failure level (77%).


Asunto(s)
Ciudades , China , Modelos Teóricos , Islas
10.
J Am Chem Soc ; 145(14): 8073-8081, 2023 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-37011903

RESUMEN

With the development of cryo-electron microscopy (cryo-EM), high-resolution structures of macromolecules can be reconstructed by the single particle method efficiently. However, challenges may still persist during the specimen preparation stage. Specifically, proteins tend to adsorb at the air-water interface and exhibit a preferred orientation in vitreous ice. To overcome these challenges, we have explored dual-affinity graphene (DAG) modified with two different affinity ligands as a supporting material for cryo-EM sample preparation. The ligands can bind to distinct sites on the corresponding tagged particles, which in turn generates various orientation distributions of particles and prevents the adsorption of protein particles onto the air-water interface. As expected, the DAG exhibited high binding specificity and affinity to target macromolecules, resulting in more balanced particle Euler angular distributions compared to single functionalized graphene on two different protein cases, including the SARS -CoV-2 spike glycoprotein. We anticipate that the DAG grids will enable facile and efficient three-dimensional (3D) reconstruction for cryo-EM structural determination, providing a robust and general technique for future studies.


Asunto(s)
COVID-19 , Grafito , Humanos , Microscopía por Crioelectrón/métodos , Grafito/química , Ligandos , Agua/química , Sustancias Macromoleculares/química
11.
Eur J Nucl Med Mol Imaging ; 50(7): 2114-2126, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36808001

RESUMEN

PURPOSE: This study was designed to compare the performance of 68Ga-FAPI-04 and 18F-FDG PET/CT for initial staging and recurrence detection of head and neck squamous cell carcinoma (HNSCC). METHODS: Prospectively, 77 patients with histologically proven or highly suspected HNSCC underwent paired 18F-FDG and 68Ga-FAPI-04 PET/CT in a week for either initial staging (n = 67) or restaging (n = 10). The diagnostic performance was compared for the two imaging approaches, especially for N staging. SUVmax, SUVmean, and target-to-background ratio (TBR) were assessed for paired positive lesions. Furthermore, change in management by 68Ga-FAPI-04 PET/CT and histopathologic FAP expression of some lesions were explored. RESULTS: 18F-FDG and 68Ga-FAPI-04 PET/CT exhibited a comparable detection efficiency for primary tumor (100%) and recurrence (62.5%). In the twenty-nine patients receiving neck dissection, 68Ga-FAPI-04 PET/CT showed greater specificity and accuracy in evaluating preoperative N staging than 18F-FDG based on patient (p = 0.031 and p = 0.070), neck side (p = 0.002 and p = 0.006), and neck level (p < 0.001 and p < 0.001). As for distant metastasis, 68Ga-FAPI-04 PET/CT detected more positive lesions than 18F-FDG (25 vs 23) and with higher SUVmax (7.99 ± 9.04 vs 3.62 ± 2.68, p = 0.002) by lesion-based analysis. The type of neck dissection in 9 cases (9/33) was altered by 68Ga-FAPI-04. Overall, clinical management was significantly changed in 10 patients (10/61). Three patients had a follow-up 68Ga-FAPI-04 PET/CT post neoadjuvant therapy: One showed complete remission, and the others showed progression. The 68Ga-FAPI-04 uptake intensity was confirmed to be consistent with FAP expression. CONCLUSION: 68Ga-FAPI-04 outperforms 18F-FDG PET/CT in evaluating preoperative N staging in patients with HNSCC. Furthermore, 68Ga-FAPI-04 PET/CT also shows the potential in clinical management and monitoring response to treatment.


Asunto(s)
Neoplasias de Cabeza y Cuello , Quinolinas , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18 , Radioisótopos de Galio , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/diagnóstico por imagen
12.
Eur J Nucl Med Mol Imaging ; 50(13): 4064-4076, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37526694

RESUMEN

PURPOSE: To compare the efficacy of [68Ga]Ga-FAPI-04 PET/CT in primary or recurrent tumors and metastatic lesions of epithelial ovarian cancer (EOC) with that of fluorine-18 fluorodeoxyglucose ([18F]F-FDG) PET/CT. METHODS: Forty-nine patients (median age, 57 years; IQR, 51-66 years) with histologically proven primary or relapsed EOC were enrolled. Participants underwent [18F]F-FDG and [68Ga]Ga-FAPI-04 PET/CT. The detection rate, diagnostic accuracy, semiquantitative parameters, tumor staging, and clinical management of the tracers were compared. The diagnostic performance of [18F]F-FDG and [68Ga]Ga-FAPI-04 PET/CT was evaluated and compared using surgical pathology. Differences between methods regarding the peritoneal cancer index (PCI) using preoperative imaging, surgical PCI, and tumor markers (CA125, HE4) were also assessed regarding peritoneal metastases. RESULTS: Among the 49 patients, 28 had primary EOC; 21 had relapsed EOC. [68Ga]Ga-FAPI-04 PET/CT outperformed [18F]F-FDG PET/CT in detecting peritoneal metastases (96.8% vs. 83.0%; p < 0.001), retroperitoneal (99.5% vs. 91.4%; p < 0.001), and supradiaphragmatic lymph node metastases (100% vs. 80.4%; p < 0.001). Compared with [18F]F-FDG, [68Ga]Ga-FAPI-04 showed higher SUVmax for peritoneal metastases (17.31 vs. 13.68; p = 0.026) and retroperitoneal (8.72 vs. 6.56; p < 0.001) and supradiaphragmatic lymph node metastases (6.39 vs. 4.20; p < 0.001). Moreover, [68Ga]Ga-FAPI-04 PET/CT showed higher sensitivity compared with [18F]F-FDG PET/CT for detecting metastatic lymph nodes (80.6% vs. 61.3%; p = 0.031) and peritoneal metastases (97.5% vs. 75.9%; p < 0.001), using surgical pathology as the gold standard. Compared with [18F]F-FDG PET/CT, [68Ga]Ga-FAPI-04 PET/CT led to an upgrade in 14.3% and 33.3% of treatment-naive and relapse participants, resulting in management changes in 10.7% and 19.0% of the patients, respectively. The median PCIFAPI scores were significantly higher than PCIFDG (15 vs. 11; p < 0.001) and positively correlated with CA125 and HE4 levels and surgical PCI. CONCLUSION: [68Ga]Ga-FAPI-04 PET/CT achieved higher sensitivity than [18F]F-FDG PET/CT in the detection and diagnosis of lymph node and peritoneal metastases, suggesting advantages regarding the preoperative staging of patients with EOC and, thereby, improving treatment decision-making. TRIAL REGISTRATION: NCT05034146. Registered February 23, 2021.


Asunto(s)
Neoplasias Ováricas , Neoplasias Peritoneales , Quinolinas , Femenino , Humanos , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18 , Radioisótopos de Galio , Carcinoma Epitelial de Ovario/diagnóstico por imagen , Metástasis Linfática/diagnóstico por imagen , Recurrencia Local de Neoplasia/diagnóstico por imagen , Neoplasias Ováricas/diagnóstico por imagen
13.
Inorg Chem ; 62(51): 21044-21052, 2023 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-38051505

RESUMEN

Lanthanide-based molecular materials showing efficient circularly polarized luminescence (CPL) activity with a high quantum yield are attractive due to their potential applications in data storage, optical sensors, and 3D displays. Herein we present an innovative method to achieve enhanced CPL activity and a high quantum yield by doping a chromophore ligand into a coordination polymer superhelix. A series of homochiral europium(III) phosphonates with a helical morphology were prepared with the molecular formula S-, R-[Eu(cyampH)3-3n(nempH)3n]·3H2O (S/R-Eu-n, n = 0-5%). The doping of chromophore ligand S- or R-nempH2 into superhelices of S/R-Eu-0% not only turned on the CPL activity with the dissymmetry factor |glum| on the order of 10-3 but also increased the quantum yield by about 14-fold. This work may shed light on the development of efficient CPL-active lanthanide-based coordination polymers for applications.

14.
J Biochem Mol Toxicol ; 37(9): e23422, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37350538

RESUMEN

Melatonin possesses potent hepatoprotective properties, but it remains to be elucidated whether melatonin has a therapeutic effect on monocrotaline (MCT)-induced hepatic sinusoidal obstruction syndrome (HSOS). In this study, male Sprague Dawley rats were intraperitoneally injected with melatonin or the same volume of vehicle at 0 and 24 h after MCT intragastric administration. Next, hematoxylin-eosin staining and electron microscopy were performed to evaluate the hepatic sinusoidal injury of rats. Endothelial cell marker RECA-1 was observed by immunohistochemistry. Hepatic oxidative stress was analyzed by detecting malondialdehyde, glutathione S-transferase, and reactive oxygen species. Assessment of liver function was carried out by analysis of serum aspartate aminotransferase, alanine aminotransferase, total bilirubin, and albumin levels. Real-time polymerase chain reaction and Western blot analysis were used to identify liver Sirtuin-3 (SIRT3) and active matrix metallopeptidase 9 (MMP-9) expression. Besides, liver sinusoidal endothelial cells (LSECs) were used for the in vitro functional verification experiment. Specifically, liver histology of the melatonin-treated groups showed that the pathological damages caused by MCT were significantly attenuated, total HSOS scores were decreased, and the elevation of serum hyaluronic acid observed in the model group was also reduced. Moreover, melatonin treatment also improved the survival of rats after partial hepatectomy. Administration of melatonin ameliorated MCT-induced LSECs injury, hepatic oxidative stress, and hepatic dysfunction. Furthermore, melatonin treatment increased SIRT3 expression while attenuating MMP-9 activity in liver tissues. Cell experiment also demonstrated that SIRT3 might mediate the protective effect of melatonin on LSECs. Collectively, our study provided the potential rationale for the application of melatonin for the prevention of MCT-induced HSOS.


Asunto(s)
Enfermedad Veno-Oclusiva Hepática , Melatonina , Sirtuina 3 , Ratas , Masculino , Animales , Enfermedad Veno-Oclusiva Hepática/inducido químicamente , Enfermedad Veno-Oclusiva Hepática/tratamiento farmacológico , Enfermedad Veno-Oclusiva Hepática/patología , Melatonina/farmacología , Melatonina/uso terapéutico , Monocrotalina/toxicidad , Sirtuina 3/metabolismo , Ratas Sprague-Dawley , Células Endoteliales/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Hígado/metabolismo
15.
Nucleic Acids Res ; 49(D1): D183-D191, 2021 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-33068412

RESUMEN

RNA molecules fold into complex structures that are important across many biological processes. Recent technological developments have enabled transcriptome-wide probing of RNA secondary structure using nucleases and chemical modifiers. These approaches have been widely applied to capture RNA secondary structure in many studies, but gathering and presenting such data from very different technologies in a comprehensive and accessible way has been challenging. Existing RNA structure probing databases usually focus on low-throughput or very specific datasets. Here, we present a comprehensive RNA structure probing database called RASP (RNA Atlas of Structure Probing) by collecting 161 deduplicated transcriptome-wide RNA secondary structure probing datasets from 38 papers. RASP covers 18 species across animals, plants, bacteria, fungi, and also viruses, and categorizes 18 experimental methods including DMS-seq, SHAPE-Seq, SHAPE-MaP, and icSHAPE, etc. Specially, RASP curates the up-to-date datasets of several RNA secondary structure probing studies for the RNA genome of SARS-CoV-2, the RNA virus that caused the on-going COVID-19 pandemic. RASP also provides a user-friendly interface to query, browse, and visualize RNA structure profiles, offering a shortcut to accessing RNA secondary structures grounded in experimental data. The database is freely available at http://rasp.zhanglab.net.


Asunto(s)
Biología Computacional/estadística & datos numéricos , Bases de Datos Genéticas/estadística & datos numéricos , Secuenciación de Nucleótidos de Alto Rendimiento/estadística & datos numéricos , Conformación de Ácido Nucleico , ARN/química , Transcriptoma , Animales , COVID-19/epidemiología , COVID-19/prevención & control , COVID-19/virología , Biología Computacional/métodos , Genoma Viral/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Pandemias , ARN/genética , Sondas ARN/genética , ARN Bacteriano/química , ARN Bacteriano/genética , ARN de Hongos/química , ARN de Hongos/genética , ARN de Planta/química , ARN de Planta/genética , ARN Viral/química , ARN Viral/genética , SARS-CoV-2/genética , SARS-CoV-2/fisiología
16.
Adv Exp Med Biol ; 1438: 65-68, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37845441

RESUMEN

People resuscitated after sudden cardiac arrest remain at high risk for mortality, with treatment for survivors varying from monitoring to life support. With respect to assessing survivability post cardiac arrest and resuscitation (CAR), we previously demonstrated the potential of the hypoxic ventilatory response (HVR) as a reliable indicator for discerning between survivors and non-survivors in the early stages of recovery following CAR in rats. Since HVR describes the increase in ventilation in response to hypoxia, we hypothesize that damage to cardiorespiratory regulatory centers in the brainstem underlie the loss of HVR observed post resuscitation in nonsurvivors. Wistar rats underwent cardiac arrest (12-min) and resuscitation. At 1 day post-resuscitation, rats were perfused transcardially and the brains were harvested and processed for immunohistostaining of caspase-3, a marker of apoptosis. Positive caspase-3 staining was observed in brainstem regions such as the rostral ventral lateral medulla (RVLM); Co-localization of caspase-3 and NeuN was observed in the RVLM as well, suggesting that apoptosis most likely occurs in neurons. Our results showed positive markers for neuronal apoptosis present in pathways of the brainstem involved in respiratory and cerebrovascular regulation, suggesting brain stem damage underlies changes in HVR following CAR.


Asunto(s)
Paro Cardíaco , Hipoxia , Humanos , Ratas , Animales , Ratas Wistar , Caspasa 3/metabolismo , Hipoxia/metabolismo , Tronco Encefálico/metabolismo , Paro Cardíaco/terapia , Respiración
17.
Adv Exp Med Biol ; 1438: 33-36, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37845436

RESUMEN

Hypoxia-inducible factor 1 (HIF-1) is a major player in the oxygen sensor system as well as a transcription factor. HIF-1 is also associated in the pathogenesis of many brain diseases including Alzheimer's disease (AD), epilepsy and stroke. HIF-1 regulates the expression of many genes such as those involved in glycolysis, erythropoiesis, angiogenesis and proliferation in hypoxic condition. Despite several studies, the mechanism through which HIF-1 confers neuroprotection remains unclear, one of them is modulating metabolic profiles and inflammatory pathways. Characterization of the neuroprotective role of HIF-1 may be through its stabilization and the regulation of target genes that aid in the early adaptation to the oxidative stressors. It is interesting to note that mounting data from recent years point to an additional crucial regulatory role for hypoxia-inducible factors (HIFs) in inflammation. HIFs in immune cells regulate the production of glycolytic energy as well as innate immunity, pro-inflammatory gene expression, and mediates activation of pro-survival pathways. The present review highlights the contribution of HIF-1 to neuroprotection where inflammation is the crucial factor in the pathogenesis contributing to neural death. The potential mechanisms that contribute to neuroprotection as a result of the downstream targets of HIF-1α are discussed. Such mechanisms include those mediated through IL-10, an anti-inflammatory molecule involved in activating pro-survival signaling mechanisms via AKT/ERK and JAK/STAT pathways.


Asunto(s)
Regulación de la Expresión Génica , Neuroprotección , Humanos , Transducción de Señal , Inflamación/genética , Fenotipo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética
18.
Altern Ther Health Med ; 29(8): 435-439, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37652413

RESUMEN

Objective: This study aims to analyze the correlation between urinary calculi formation and Traditional Chinese Medicine (TCM) constitution among individuals in Wuhu. Methods: This retrospective study was conducted at our hospital from December 2020 to December 2021. A total of 140 cases were selected for the study population. The patients underwent thorough clinical and statistical analysis, and their TCM constitution classification was determined based on TCM constitution theory. Additionally, the study assessed the urinary stone composition of these 140 patients using the SUN-3G intelligent stone analyzer. Results: Among the 140 patients, the largest group comprised patients with a peaceful constitution, accounting for 36.43%. The second largest group, at 23.57%, included patients with constitution type A (peaceful + any other TCM constitution). Following that, patients with constitution type A G (Yang deficiency + any other TCM constitution) represented the third largest group at 7.14%. Conclusions: The majority of patients demonstrated a constitution characterized by peace and substance. Therefore, it is imperative to allocate medical resources strategically to enhance the effectiveness of Traditional Chinese Medicine syndrome differentiation in treatment.


Asunto(s)
Medicina Tradicional China , Urolitiasis , Humanos , Adulto , Estudios Retrospectivos , Urolitiasis/epidemiología , China
19.
Entropy (Basel) ; 25(5)2023 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-37238516

RESUMEN

Orthogonal time-frequency space (OTFS) modulation has been advocated as a promising waveform for achieving integrated sensing and communication (ISAC) due to its superiority in high-mobility adaptability and spectral efficiency. In OTFS modulation-based ISAC systems, accurate channel acquisition is critical for both communication reception and sensing parameter estimation. However, the existence of the fractional Doppler frequency shift spreads the effective channels of the OTFS signal significantly, making efficient channel acquisition very challenging. In this paper, we first derive the sparse structure of the channel in the delay Doppler (DD) domain according to the input and output relationship of OTFS signals. On this basis, a new structured Bayesian learning approach is proposed for accurate channel estimation, which includes a novel structured prior model for the delay-Doppler channel and a successive majorization-minimization (SMM) algorithm for efficient posterior channel estimate computation. Simulation results show that the proposed approach significantly outperforms the reference schemes, especially in the low signal-to-noise ratio (SNR) region.

20.
Angew Chem Int Ed Engl ; 62(40): e202308454, 2023 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-37563746

RESUMEN

Metallic zinc (Zn) is considered as one of the most attractive anode materials for the post-lithium metal battery systems owing to the high theoretical capacity, low cost, and intrinsic safety. However, the Zn dendrites and parasitic side reaction impede its application. Herein, we propose a new principle of regulating p-band center of metal oxide protective coating to balance Zn adsorption energy and migration energy barrier for effective Zn deposition and stripping. Experimental results and theoretical calculations indicate that benefiting from the uniform zincophilic nucleation sites and fast Zn transport on indium tin oxide (ITO), highly stable and reversible Zn anode can be achieved. As a result, the I-Zn symmetrical cell achieves highly reversible Zn deposition/stripping with an extremely low overpotential of 9 mV and a superior lifespan over 4000 h. The Cu/I-Zn asymmetrical cell exhibits a long lifetime of over 4000 cycles with high average coulombic efficiency of 99.9 %. Furthermore, the assembled I-Zn/AC full cell exhibits an excellent lifetime for 70000 cycles with nearly 100 % capacity retention. This work provides a general strategy and new insight for the construction of efficient Zn anode protection layer.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA