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1.
Nat Immunol ; 22(1): 25-31, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33154590

RESUMEN

Clinical manifestations of COVID-19 caused by the new coronavirus SARS-CoV-2 are associated with age1,2. Adults develop respiratory symptoms, which can progress to acute respiratory distress syndrome (ARDS) in the most severe form, while children are largely spared from respiratory illness but can develop a life-threatening multisystem inflammatory syndrome (MIS-C)3-5. Here, we show distinct antibody responses in children and adults after SARS-CoV-2 infection. Adult COVID-19 cohorts had anti-spike (S) IgG, IgM and IgA antibodies, as well as anti-nucleocapsid (N) IgG antibody, while children with and without MIS-C had reduced breadth of anti-SARS-CoV-2-specific antibodies, predominantly generating IgG antibodies specific for the S protein but not the N protein. Moreover, children with and without MIS-C had reduced neutralizing activity as compared to both adult COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children independent of whether they develop MIS-C, with implications for developing age-targeted strategies for testing and protecting the population.


Asunto(s)
Anticuerpos Antivirales/inmunología , Formación de Anticuerpos/inmunología , COVID-19/inmunología , Proteínas de la Nucleocápside/inmunología , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Adolescente , Adulto , Anciano , COVID-19/virología , Niño , Preescolar , Femenino , Humanos , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Masculino , Persona de Mediana Edad , SARS-CoV-2/fisiología , Adulto Joven
2.
Cell ; 153(5): 1134-48, 2013 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-23664764

RESUMEN

Epigenetic mechanisms have been proposed to play crucial roles in mammalian development, but their precise functions are only partially understood. To investigate epigenetic regulation of embryonic development, we differentiated human embryonic stem cells into mesendoderm, neural progenitor cells, trophoblast-like cells, and mesenchymal stem cells and systematically characterized DNA methylation, chromatin modifications, and the transcriptome in each lineage. We found that promoters that are active in early developmental stages tend to be CG rich and mainly engage H3K27me3 upon silencing in nonexpressing lineages. By contrast, promoters for genes expressed preferentially at later stages are often CG poor and primarily employ DNA methylation upon repression. Interestingly, the early developmental regulatory genes are often located in large genomic domains that are generally devoid of DNA methylation in most lineages, which we termed DNA methylation valleys (DMVs). Our results suggest that distinct epigenetic mechanisms regulate early and late stages of ES cell differentiation.


Asunto(s)
Metilación de ADN , Células Madre Embrionarias/metabolismo , Epigenómica , Regulación del Desarrollo de la Expresión Génica , Animales , Diferenciación Celular , Cromatina/metabolismo , Islas de CpG , Células Madre Embrionarias/citología , Histonas/metabolismo , Humanos , Metilación , Neoplasias/genética , Regiones Promotoras Genéticas , Pez Cebra/embriología
3.
Nat Methods ; 20(2): 276-283, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36646897

RESUMEN

Cryo-electron tomography (cryo-ET) has become a powerful approach to study the high-resolution structure of cellular macromolecular machines in situ. However, the current correlative cryo-fluorescence and electron microscopy lacks sufficient accuracy and efficiency to precisely prepare cryo-lamellae of target locations for subsequent cryo-ET. Here we describe a precise cryogenic fabrication system, ELI-TriScope, which sets electron (E), light (L) and ion (I) beams at the same focal point to achieve accurate and efficient preparation of a target cryo-lamella. ELI-TriScope uses a commercial dual-beam scanning electron microscope modified to incorporate a cryo-holder-based transfer system and embed an optical imaging system just underneath the vitrified specimen. Cryo-focused ion beam milling can be accurately navigated by monitoring the real-time fluorescence signal of the target molecule. Using ELI-TriScope, we prepared a batch of cryo-lamellae of HeLa cells targeting the centrosome with a success rate of ~91% and discovered new in situ structural features of the human centrosome by cryo-ET.


Asunto(s)
Tomografía con Microscopio Electrónico , Electrones , Humanos , Tomografía con Microscopio Electrónico/métodos , Microscopía por Crioelectrón/métodos , Células HeLa , Sustancias Macromoleculares
4.
J Biol Chem ; 299(6): 104752, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37100288

RESUMEN

Homologs of the protein Get3 have been identified in all domains yet remain to be fully characterized. In the eukaryotic cytoplasm, Get3 delivers tail-anchored (TA) integral membrane proteins, defined by a single transmembrane helix at their C terminus, to the endoplasmic reticulum. While most eukaryotes have a single Get3 gene, plants are notable for having multiple Get3 paralogs. Get3d is conserved across land plants and photosynthetic bacteria and includes a distinctive C-terminal α-crystallin domain. After tracing the evolutionary origin of Get3d, we solve the Arabidopsis thaliana Get3d crystal structure, identify its localization to the chloroplast, and provide evidence for a role in TA protein binding. The structure is identical to that of a cyanobacterial Get3 homolog, which is further refined here. Distinct features of Get3d include an incomplete active site, a "closed" conformation in the apo-state, and a hydrophobic chamber. Both homologs have ATPase activity and are capable of binding TA proteins, supporting a potential role in TA protein targeting. Get3d is first found with the development of photosynthesis and conserved across 1.2 billion years into the chloroplasts of higher plants across the evolution of photosynthesis suggesting a role in the homeostasis of photosynthetic machinery.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Fotosíntesis , Adenosina Trifosfatasas/metabolismo , Embryophyta , Retículo Endoplásmico/metabolismo , Factores de Intercambio de Guanina Nucleótido/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo
5.
Small ; 20(8): e2305765, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37821399

RESUMEN

Solid proton electrolytes play a crucial role in various electrochemical energy storage and conversion devices. However, the development of fast proton conducting solid proton electrolytes at ambient conditions remains a significant challenge. In this study, a novel acidified nitrogen self-doped porous carbon material is presented that demonstrates exceptional superprotonic conduction for applications in solid-state proton battery. The material, designated as MSA@ZIF-8-C, is synthesized through the acidification of nitrogen-doped porous carbon, specifically by integrating methanesulfonic acid (MSA) into zeolitic imidazolate framework-derived nitrogen self-doped porous carbons (ZIF-8-C). This study reveals that MSA@ZIF-8-C achieves a record-high proton conductivity beyond 10-2  S cm-1 at ambient condition, along with good long-term stability, positioning it as a cutting-edge alternative solid proton electrolyte to the default aqueous H2 SO4 electrolyte in proton batteries.

6.
Opt Express ; 32(4): 4887-4901, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38439229

RESUMEN

In underwater wireless optical communication, orbital angular momentum (OAM) states suffer from turbulence distortions. This study aims to investigate the effectiveness of auto-focusing and OAM entanglement of the beams in reducing the turbulence effects. We implement the single-phase approximation and the extended Huygens-Fresnel principle to derive the detection probability of the entangled Airy beams under unstable oceanic turbulence. The results show that auto-focusing can protect the signal OAM mode and suppress modal crosstalks, while entangled OAM states can further enhance the resistance against oceanic turbulence around the focus position. The numerical analysis demonstrates that after the auto-focusing position, the beams evolve in completely opposite directions, indicating that the focal length should be modulated according to the length of a practical link to enhance received signals. These findings suggest that entangled auto-focusing vortex beams may be a desirable light source in underwater communication systems.

7.
BMC Cancer ; 24(1): 246, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38388861

RESUMEN

BACKGROUND: Artificial intelligence (AI)-assisted clinical trial screening is a promising prospect, although previous matching systems were developed in English, and relevant studies have only been conducted in Western countries. Therefore, we evaluated an AI-based clinical trial matching system (CTMS) that extracts medical data from the electronic health record system and matches them to clinical trials automatically. METHODS: This study included 1,053 consecutive inpatients primarily diagnosed with hepatocellular carcinoma who were referred to the liver tumor center of an academic medical center in China between January and December 2019. The eligibility criteria extracted from two clinical trials, patient attributes, and gold standard were decided manually. We evaluated the performance of the CTMS against the established gold standard by measuring the accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and run time required. RESULTS: The manual reviewers demonstrated acceptable interrater reliability (Cohen's kappa 0.65-0.88). The performance results for the CTMS were as follows: accuracy, 92.9-98.0%; sensitivity, 51.9-83.5%; specificity, 99.0-99.1%; PPV, 75.7-85.1%; and NPV, 97.4-98.9%. The time required for eligibility determination by the CTMS and manual reviewers was 2 and 150 h, respectively. CONCLUSIONS: We found that the CTMS is particularly reliable in excluding ineligible patients in a significantly reduced amount of time. The CTMS excluded ineligible patients for clinical trials with good performance, reducing 98.7% of the work time. Thus, such AI-based systems with natural language processing and machine learning have potential utility in Chinese clinical trials.


Asunto(s)
Inteligencia Artificial , Carcinoma Hepatocelular , Neoplasias Hepáticas , Selección de Paciente , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , China/epidemiología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Reproducibilidad de los Resultados , Estudios Retrospectivos , Ensayos Clínicos como Asunto , Hospitalización
8.
Liver Int ; 44(6): 1435-1447, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38483145

RESUMEN

BACKGROUND AND AIMS: The use of corticosteroids in chronic drug-induced liver injury (DILI) is an important issue. Our previous randomized controlled trial showed that patients with chronic DILI benefited from a 48-week steroid stepwise reduction (SSR) regimen. However, it remains unclear whether a shorter course of therapy can achieve similar efficacy. In this study, we aimed to assess whether a 36-week SSR can achieve efficacy similar to that of 48-week SSR. METHODS: A randomized open-label trial was performed. Eligible patients were randomly assigned to the 36- or 48-week (1:1) SSR group. Liver biopsies were performed at baseline and at the end of treatment. The primary outcome was the proportion of patients with relapse rate (RR). The secondary outcomes were improvement in liver histology and safety. RESULTS: Of the 90 participants enrolled, 84 (87.5%) completed the trial, and 62 patients (68.9%) were women. Hepatocellular damage was observed in 53.4% of the cohort. The RR was 7.1% in the 36-week SSR group but 4.8% in the 48-week SSR group, as determined by per-protocol set analysis (p = 1.000). Significant histological improvements in histological activity (93.1% vs. 92.9%, p = 1.000) and fibrosis (41.4% vs. 46.4%, p = .701) were observed in both the groups. Biochemical normalization time did not differ between the two groups. No severe adverse events were observed. CONCLUSIONS: Both the 36- and 48-week SSR regimens demonstrated similar biochemical response and histological improvements with good safety, supporting 36-week SSR as a preferable therapeutic choice (ClinicalTrials.gov, NCT03266146).


Asunto(s)
Hígado , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto , Hígado/patología , Hígado/efectos de los fármacos , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/etiología , Resultado del Tratamiento , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Recurrencia , Anciano , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Esquema de Medicación
9.
Pediatr Res ; 95(4): 959-965, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38012310

RESUMEN

BACKGROUND: Tie2, a functional angiopoietin receptor, is expressed in vascular endothelial cells and plays an important role in angiogenesis and vascular stability. This study aimed to evaluate the effects of an agonistic Tie2 signal on renal interstitial fibrosis (RIF) and elucidate the underlying mechanisms. METHODS: We established an in vivo mouse model of folic acid-induced nephropathy (FAN) and an in vitro model of lipopolysaccharide-stimulated endothelial cell injury, then an agonistic Tie2 monoclonal antibody (Tie2 mAb) was used to intervent these processes. The degree of tubulointerstitial lesions and related molecular mechanisms were determined by histological assessment, immunohistochemistry, western blotting, and qPCR. RESULTS: Tie2 mAb attenuated RIF and reduced the level of fibroblast-specific protein 1 (FSP1). Further, it suppressed vascular cell adhesion molecule-1 (VCAM-1) and increased CD31 density in FAN. In the in vitro model, Tie2 mAb was found to decrease the expression of VCAM-1, Bax, and α-smooth muscle actin (α-SMA). CONCLUSIONS: The present findings indicate that the agonistic Tie2 mAb exerted vascular protective effects and ameliorated RIF via inhibition of vascular inflammation, apoptosis, and fibrosis. Therefore, Tie2 may be a potential target for the treatment of this disease. IMPACT: This is the first report to confirm that an agonistic Tie2 monoclonal antibody can reduce renal interstitial fibrosis in folic acid-induced nephropathy in mice. This mechanism possibly involves vascular protective effects brought about by inhibition of vascular inflammation, apoptosis and fibrosis. Our data show that Tie2 signal may be a novel, endothelium-specific target for the treatment of tubulointerstitial fibrosis.


Asunto(s)
Células Endoteliales , Enfermedades Renales , Ratones , Animales , Células Endoteliales/metabolismo , Receptor TIE-2/metabolismo , Molécula 1 de Adhesión Celular Vascular , Fibrosis , Anticuerpos Monoclonales/farmacología , Enfermedades Renales/inducido químicamente , Ácido Fólico , Inflamación , Angiopoyetina 1 , Angiopoyetina 2
10.
J Gastroenterol Hepatol ; 39(6): 1134-1144, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38615196

RESUMEN

BACKGROUND AND AIM: Small heterodimer partner (SHP, encoded by NR0B2) plays an important role in maintaining bile acid homeostasis. The loss of the hepatic farnesoid X receptor (FXR)/SHP signal can cause severe cholestatic liver injury (CLI). FXR and SHP have overlapping and nonoverlapping functions in bile acid homeostasis. However, the key role played by SHP in CLI is unclear. METHODS: In this study, an alpha-naphthylisothiocyanate (ANIT)-induced cholestasis mouse model was established. The effect of SHP knockout (SHP-KO) on liver and ileal pathology was evaluated. 16S rRNA gene sequencing analysis combined with untargeted metabolomics was applied to reveal the involvement of SHP in the pathogenesis of CLI. RESULTS: The results showed that ANIT (75 mg/kg) induced cholestasis in WT mice. No significant morphological changes were found in the liver and ileal tissue of SHP-KO mice. However, the serum metabolism and intestinal flora characteristics were significantly changed. Moreover, compared with the WT + ANIT group, the serum levels of ALT and AST in the SHP-KO + ANIT group were significantly increased, and punctate necrosis in the liver tissue was more obvious. The ileum villi showed obvious shedding, thinning, and shortening. In addition, SHP-KO-associated differential intestinal flora and differential biomarkers were significantly associated. CONCLUSION: In this study, we elucidated the serum metabolic characteristics and intestinal flora changes related to the aggravation of CLI in SHP-KO mice induced by ANIT.


Asunto(s)
1-Naftilisotiocianato , Colestasis , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Hígado , Ratones Noqueados , Receptores Citoplasmáticos y Nucleares , Animales , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores Citoplasmáticos y Nucleares/genética , Colestasis/metabolismo , Colestasis/patología , Hígado/patología , Hígado/metabolismo , 1-Naftilisotiocianato/toxicidad , Masculino , Íleon/patología , Íleon/metabolismo , Microbioma Gastrointestinal , Ratones , Ácidos y Sales Biliares/metabolismo , Ratones Endogámicos C57BL
11.
J Opt Soc Am A Opt Image Sci Vis ; 41(6): B106-B115, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38856418

RESUMEN

The evolution of the information transfer capability of an optical system for underwater focused wave mode localized wave (FWMLW) in anisotropic weakly turbulent absorbing seawater is studied. By developing the probability distribution function as well as the detection probability of the vortex modes carried by the FWMLW and the average bit error rate of the FWMLW underwater system, the information capacity of the FWMLW system with a pointing error is modeled. Through a numerical analysis of the effects of turbulent seawater and optical system parameters on the built light intensity, the detection probability, and the information capacity models, we find that the FWMLW system has an optimal delay time determined by the spectrum bandwidth when the spectrum bandwidth is greater than 1. The information capacity of the FWMLW system is higher than that of the X localized wave system under the same turbulent seawater channel condition, and FWMLW is a better optical signal source for vortex mode division multiplexing underwater systems than a Bessel-Gaussian beam.

12.
J Opt Soc Am A Opt Image Sci Vis ; 41(5): 943-951, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38856580

RESUMEN

Compared to horizontal transmission, the oceanic dissipation rate and temperature-salinity distribution ratio are no longer constant but vary with depth, imposing greater complexity on oceanic turbulence when beams propagate through a slant path and resulting in more limitations on the performance of underwater wireless optical communication (UWOC) links. This study focuses on investigating the performance, especially the auto-focusing characteristic, of auto-focusing hypergeometric Gaussian (AHGG) beams propagating along slant paths in oceanic turbulence. We theoretically derive the spatial coherence radius and the relative probability of the orbital angular momentum (OAM) mode for AHGG beams passing through such links. Numerical simulations reveal that AHGG beams exhibit superior propagation performance compared to hypergeometric Gaussian beams. Lower beam orders and OAM numbers contribute to improved performance, while careful selection of auto-focusing length can tangibly enhance detection performance as well. Additionally, tidal velocities and wind speeds have nonnegligible effects on OAM signal probability. Our results further demonstrate that surface buoyancy flux, temperature gradients, and waterside friction velocity significantly affect beam transmission under varying wind conditions. These findings, particularly controlling the auto-focusing length of AHGG beams to match the transmission distance, provide valuable insights for enhancing the quality of UWOC links.

13.
Mol Cell ; 62(2): 284-294, 2016 04 21.
Artículo en Inglés | MEDLINE | ID: mdl-27105118

RESUMEN

Natural variations in gene expression provide a mechanism for multiple phenotypes to arise in an isogenic bacterial population. In particular, a sub-group termed persisters show high tolerance to antibiotics. Previously, their formation has been attributed to cell dormancy. Here we demonstrate that bacterial persisters, under ß-lactam antibiotic treatment, show less cytoplasmic drug accumulation as a result of enhanced efflux activity. Consistently, a number of multi-drug efflux genes, particularly the central component TolC, show higher expression in persisters. Time-lapse imaging and mutagenesis studies further establish a positive correlation between tolC expression and bacterial persistence. The key role of efflux systems, among multiple biological pathways involved in persister formation, indicates that persisters implement a positive defense against antibiotics prior to a passive defense via dormancy. Finally, efflux inhibitors and antibiotics together effectively attenuate persister formation, suggesting a combination strategy to target drug tolerance.


Asunto(s)
Antibacterianos/farmacología , Proteínas de la Membrana Bacteriana Externa/metabolismo , Compuestos de Boro/farmacología , Farmacorresistencia Bacteriana , Proteínas de Escherichia coli/metabolismo , Escherichia coli/efectos de los fármacos , Proteínas de Transporte de Membrana/metabolismo , Penicilinas/farmacología , Antibacterianos/metabolismo , Proteínas de la Membrana Bacteriana Externa/genética , Transporte Biológico , Compuestos de Boro/metabolismo , Recuento de Colonia Microbiana , Relación Dosis-Respuesta a Droga , Farmacorresistencia Bacteriana/genética , Escherichia coli/genética , Escherichia coli/crecimiento & desarrollo , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Regulación Bacteriana de la Expresión Génica , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Proteínas de Transporte de Membrana/genética , Viabilidad Microbiana/efectos de los fármacos , Mutación , Imagen Óptica , Penicilinas/metabolismo , Fenotipo , Factores de Tiempo , Regulación hacia Arriba
14.
Mol Cell ; 61(3): 461-473, 2016 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-26833089

RESUMEN

Detailed genomic contact maps have revealed that chromosomes are structurally organized in megabase-sized topologically associated domains (TADs) that encompass smaller subTADs. These domains segregate in the nuclear space to form active and inactive nuclear compartments, but cause and consequence of compartmentalization are largely unknown. Here, we combined lacO/lacR binding platforms with allele-specific 4C technologies to track their precise position in the three-dimensional genome upon recruitment of NANOG, SUV39H1, or EZH2. We observed locked genomic loci resistant to spatial repositioning and unlocked loci that could be repositioned to different nuclear subcompartments with distinct chromatin signatures. Focal protein recruitment caused the entire subTAD, but not surrounding regions, to engage in new genomic contacts. Compartment switching was found uncoupled from transcription changes, and the enzymatic modification of histones per se was insufficient for repositioning. Collectively, this suggests that trans-associated factors influence three-dimensional compartmentalization independent of their cis effect on local chromatin composition and activity.


Asunto(s)
Núcleo Celular/metabolismo , Segregación Cromosómica , Células Madre Embrionarias/metabolismo , Sitios Genéticos , Operón Lac , Represoras Lac/metabolismo , Animales , Células Cultivadas , Cromatina/metabolismo , Ensamble y Desensamble de Cromatina , Proteína Potenciadora del Homólogo Zeste 2 , Regulación de la Expresión Génica , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Represoras Lac/genética , Metiltransferasas/genética , Metiltransferasas/metabolismo , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Proteína Homeótica Nanog , Complejo Represivo Polycomb 2/genética , Complejo Represivo Polycomb 2/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Transfección
15.
Clin Oral Implants Res ; 35(4): 454-466, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38345170

RESUMEN

OBJECTIVES: To determine the optimal current and time of electrolytic cleaning (EC), compare its biofilm removal effect with generic treatments and evaluate the influence of EC to surface characteristics and osteogenic potential of SLA titanium (Ti) discs. MATERIALS AND METHODS: The six-species biofilm-covered Ti discs were placed as cathodes in physiologic saline and subjected to various current and time treatments. The residual biofilms were evaluated to determine the optimal parameters. The contaminated Ti discs were randomized and treated by rotating Ti brush; ultrasonic-scaling with metal tips; ultrasonic-scaling with PEEK tips; air-polishing and EC. The residual biofilms were compared using a lipopolysaccharide kit (LPS), scanning electron microscope (SEM), confocal laser scanning microscopy and colony-forming unit counting. Non-contaminated Ti discs were treated and characterized. The bone marrow mesenchymal stem cells (BMSCs) were cultured on treated non-contaminated Ti discs. The adhesion, proliferation, alkaline phosphatase (ALP) activity and osteocalcin level of BMSCs were assessed. RESULTS: The parameters at 0.6A5min were considered optimal. For LPS and SEM, EC promoted a significantly greater biofilm removal than the other groups. There were no changes in the Ti discs' colour, topography, roughness and chemical elements after EC, and the electrolysis-treated Ti discs obtained a super-hydrophilic surface. EC positively impacted the proliferation and ALP activity of BMSCs, surpassing the efficacy of alternative treatments. CONCLUSIONS: EC achieves a near-complete eradication of contaminants on the SLA surface, causes no surface damage with improved hydrophilicity, and promotes the early osteogenic response of BMSCs, which makes it a promising treatment for peri-implantitis.


Asunto(s)
Implantes Dentales , Periimplantitis , Humanos , Titanio/química , Lipopolisacáridos/farmacología , Osteogénesis , Biopelículas , Propiedades de Superficie , Microscopía Electrónica de Rastreo
16.
J Nanobiotechnology ; 22(1): 52, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38321555

RESUMEN

Bacterial cystitis, a commonly occurring urinary tract infection (UTI), is renowned for its extensive prevalence and tendency to recur. Despite the extensive utilization of levofloxacin as a conventional therapeutic approach for bacterial cystitis, its effectiveness is impeded by adverse toxic effects, drug resistance concerns, and its influence on the gut microbiota. This study introduces Lev@PADM, a hydrogel with antibacterial properties that demonstrates efficacy in the treatment of bacterial cystitis. Lev@PADM is produced by combining levofloxacin with decellularized porcine acellular dermal matrix hydrogel and exhibits remarkable biocompatibility. Lev@PADM demonstrates excellent stability as a hydrogel at body temperature, enabling direct administration to the site of infection through intravesical injection. This localized delivery route circumvents the systemic circulation of levofloxacin, resulting in a swift and substantial elevation of the antimicrobial agent's concentration specifically at the site of infection. The in vivo experimental findings provide evidence that Lev@PADM effectively prolongs the duration of levofloxacin's action, impedes the retention and invasion of E.coli in the urinary tract, diminishes the infiltration of innate immune cells into infected tissues, and simultaneously preserves the composition of the intestinal microbiota. These results indicate that, in comparison to the exclusive administration of levofloxacin, Lev@PADM offers notable benefits in terms of preserving the integrity of the bladder epithelial barrier and suppressing the recurrence of urinary tract infections.


Asunto(s)
Dermis Acelular , Cistitis , Infecciones Urinarias , Porcinos , Animales , Levofloxacino , Hidrogeles
17.
Ophthalmic Res ; 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38555640

RESUMEN

INTRODUCTION: This study aimed to investigate the relationship between age of myopia onset and high myopia and to explore if age of onset mediated the associations of high myopia with parental myopia and time spent on electronics. METHODS: This cross-sectional study enrolled 1118 myopic patients aged 18 to 40. Information was obtained via a detailed questionnaire. Multivariable logistic regression and linear regression models were utilized to assess age of onset in relation to high myopia and spherical equivalent refractive error, respectively. Structural equation models examined the mediated effect of onset age on the association between parental myopia, time spent on electronics and high myopia. RESULTS: An early age at myopia onset was negatively correlated with spherical equivalent refractive power. Subjects who developed myopia before the age of 12 were more likely to suffer from high myopia than those who developed myopia after the age of 15. Age of myopia onset was the strongest predictor of high myopia, with an area under the curve (AUC) in Receiver Operator Characteristic (ROC) analysis of 0.80. Additionally, age of myopia onset served as a mediator in the relationships between parental myopia, electronic device usage duration, and the onset of high myopia in adulthood. CONCLUSIONS: Age of myopia onset might be the single best predictor for high myopia, and age at onset appeared to mediate the associations of high myopia with parental myopia and time spent on electronics.

18.
Proc Natl Acad Sci U S A ; 118(48)2021 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-34782481

RESUMEN

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mediates membrane fusion to allow entry of the viral genome into host cells. To understand its detailed entry mechanism and develop a specific entry inhibitor, in situ structural information on the SARS-CoV-2 spike protein in different states is urgent. Here, by using cryo-electron tomography, we observed both prefusion and postfusion spikes in ß-propiolactone-inactivated SARS-CoV-2 virions and solved the in situ structure of the postfusion spike at nanometer resolution. Compared to previous reports, the six-helix bundle fusion core, the glycosylation sites, and the location of the transmembrane domain were clearly resolved. We observed oligomerization patterns of the spikes on the viral membrane, likely suggesting a mechanism of fusion pore formation.


Asunto(s)
SARS-CoV-2/ultraestructura , Glicoproteína de la Espiga del Coronavirus/química , Secuencias de Aminoácidos , Animales , Chlorocebus aethiops , Microscopía por Crioelectrón , Tomografía con Microscopio Electrónico , Glicosilación , Dominios Proteicos , Multimerización de Proteína , Glicoproteína de la Espiga del Coronavirus/metabolismo , Células Vero
19.
Aesthetic Plast Surg ; 48(3): 501-509, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38200124

RESUMEN

BACKGROUND: Autologous adipose tissue often experiences ischemia and hypoxia after transplantation, leading to low retention rates and unstable operative impacts due to necrotic absorption. Platelet-rich plasma (PRP) can enhance fat regeneration and increase the fat retention rate after transplantation. However, the quick release of growth factors (GFs) in PRP decreases therapeutic efficiency. This study aimed to achieve a slow release of PRP to promote fat retention. METHODS: We prepared a dual-network hydrogel (DN gel) based on FDA-approved PRP and sodium alginate (SA) through a simple "one-step" activation process. In vivo study, adipose tissue with saline (control group), SA gel (SA gel group), PRP gel (PRP gel group), and DN gel (DN gel group) was injected subcutaneously into the dorsum of nude mice. At 4 and 12 weeks after injection, tissues were assessed for volume and weight. Hematoxylin and eosin staining (HE) and immunofluorescence staining were performed for histological assessment. RESULTS: DN gel exhibits long-lasting growth factor effects, surpassing conventional clinical PRP gel regarding vascularization potential. In fat transplantation experiments, DN gel demonstrated improved vascularization of transplanted fat and increased retention rates, showing promise for clinical applications. CONCLUSIONS: DN gel-assisted lipofilling can significantly improve the retention rate and quality of transplanted fat. DN gel-assisted lipofilling, which is considered convenient, is a promising technique to improve neovascularization and fat survival. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.


Asunto(s)
Tejido Adiposo , Plasma Rico en Plaquetas , Animales , Ratones , Ratones Desnudos , Tejido Adiposo/trasplante , Inyecciones
20.
Int J Mol Sci ; 25(6)2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38542477

RESUMEN

Based on Sima and Lu's system of the family Magnoliaceae, the genus Lirianthe Spach s. l. includes approximately 25 species, each with exceptional landscaping and horticultural or medical worth. Many of these plants are considered rare and are protected due to their endangered status. The limited knowledge of species within this genus and the absence of research on its chloroplast genome have greatly impeded studies on the relationship between its evolution and systematics. In this study, the chloroplast genomes of eight species from the genus Lirianthe were sequenced and analyzed, and their phylogenetic relationships with other genera of the family Magnoliaceae were also elucidated. The results showed that the chloroplast genome sizes of the eight Lirianthe species ranged from 159,548 to 159,833 bp. The genomes consisted of a large single-copy region, a small single-copy region, and a pair of inverted repeat sequences. The GC content was very similar across species. Gene annotation revealed that the chloroplast genomes contained 85 protein-coding genes, 37 tRNA genes, and 8 rRNA genes, totaling 130 genes. Codon usage analysis indicated that codon usage was highly conserved among the eight Lirianthe species. Repeat sequence analysis identified 42-49 microsatellite sequences, 16-18 tandem repeats, and 50 dispersed repeats, with microsatellite sequences being predominantly single-nucleotide repeats. DNA polymorphism analysis revealed 10 highly variable regions located in the large single-copy and small single-copy regions, among which rpl32-trnL, petA-psbJ, and trnH-psbA were the recommended candidate DNA barcodes for the genus Lirianthe species. The inverted repeat boundary regions show little variation between species and are generally conserved. The result of phylogenetic analysis confirmed that the genus Lirianthe s. l. is a monophyletic taxon and the most affinal to the genera, Talauma and Dugandiodendron, in Sima and Lu's system and revealed that the genus Lirianthe s. s. is paraphyletic and the genus Talauma s. l. polyphyletic in Xia's system, while Magnolia subsection Gwillimia is paraphyletic and subsection Blumiana polyphyletic in Figlar and Nooteboom's system. Morphological studies found noticeable differences between Lirianthe species in aspects including leaf indumentum, stipule scars, floral orientation, tepal number, tepal texture, and fruit dehiscence. In summary, this study elucidated the chloroplast genome evolution within Lirianthe and laid a foundation for further systematic and taxonomic research on this genus.


Asunto(s)
Genoma del Cloroplasto , Magnolia , Filogenia , Anotación de Secuencia Molecular , Plantas/genética
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