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1.
Nucleic Acids Res ; 52(9): 4843-4856, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38647109

RESUMEN

Spatial transcriptome technologies have enabled the measurement of gene expression while maintaining spatial location information for deciphering the spatial heterogeneity of biological tissues. However, they were heavily limited by the sparse spatial resolution and low data quality. To this end, we develop a spatial location-supervised auto-encoder generator STAGE for generating high-density spatial transcriptomics (ST). STAGE takes advantage of the customized supervised auto-encoder to learn continuous patterns of gene expression in space and generate high-resolution expressions for given spatial coordinates. STAGE can improve the low quality of spatial transcriptome data and smooth the generated manifold of gene expression through the de-noising function on the latent codes of the auto-encoder. Applications to four ST datasets, STAGE has shown better recovery performance for down-sampled data than existing methods, revealed significant tissue structure specificity, and enabled robust identification of spatially informative genes and patterns. In addition, STAGE can be extended to three-dimensional (3D) stacked ST data for generating gene expression at any position between consecutive sections for shaping high-density 3D ST configuration.


Asunto(s)
Perfilación de la Expresión Génica , Transcriptoma , Transcriptoma/genética , Perfilación de la Expresión Génica/métodos , Humanos , Animales , Algoritmos , Programas Informáticos
2.
Nucleic Acids Res ; 51(5): 2137-2150, 2023 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-36718943

RESUMEN

Transcriptional Mediator controls diverse gene programs for various developmental and pathological processes. The human Mediator MED23/R617Q mutation was reported in a familial intellectual disability (ID) disorder, although the underlying mechanisms remain poorly understood. Constructed by gene editing, the Med23/R617Q knock-in mutant mice exhibited embryonic lethality due to the largely reduced Med23/R617Q protein level, but the R617Q mutation in HEK293T cells didn't change its expression and incorporation into Mediator Complex. RNA-seq revealed that MED23/R617Q mutation disturbed gene expression, related to neural development, learning and memory. Specifically, R617Q mutation reduced the MED23-dependent activities of ELK1 and E1A, but in contrast, upregulated the MAPK/ELK1-driven early immediate genes (IEGs) JUN and FOS. ChIP-seq and Hi-C revealed that the MED23 R617Q mutation reprogramed a subset of enhancers and local chromatin interactions, which correlated well with the corresponding gene expression. Importantly, the enhancers and chromatin interactions surrounding IEGs were unchanged by the R617Q mutation, but DACH1, an upstream repressor of IEGs, showed reduced enhancer-promoter interactions and decreased expression in mutant cells, thus relieving its inhibition to the intellectual-related IEGs. Overall, unraveling the MED23-DACH1-IEG axis provides a mechanistic explanation for the effects of the MED23/R617Q mutation on gene dysregulation and inherited ID.


Asunto(s)
Discapacidad Intelectual , Complejo Mediador , Animales , Humanos , Ratones , Cromatina/genética , Expresión Génica , Células HEK293 , Discapacidad Intelectual/genética , Complejo Mediador/genética , Complejo Mediador/metabolismo , Mutación
3.
Anal Chem ; 96(6): 2327-2332, 2024 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-38308847

RESUMEN

Interference from nonspecific binding imposes a fundamental limit in the sensitivity of biosensors that is dependent on the affinity and specificity of the available sensing probes. The dynamic single-molecule sensing (DSMS) strategy allows ultrasensitive detection of biomarkers at the femtomolar level by identifying specific binding according to molecular binding traces. However, the accuracy in classifying binding traces is not sufficient from separate features, such as the bound lifetime. Here, we establish a DSMS workflow to improve the sensitivity and linearity by classifying molecular binding traces in surface plasmon resonance microscopy with multiple kinetic features. The improvement is achieved by correlation analysis to select key features of binding traces, followed by unsupervised k-clustering. The results show that this unsupervised classification approach improves the sensitivity and linearity in microRNA (hsa-miR155-5p, hsa-miR21-5p, and hsa-miR362-5p) detection to achieve a limit of detection at the subfemtomolar level.


Asunto(s)
Técnicas Biosensibles , MicroARNs , MicroARNs/genética , Técnicas Biosensibles/métodos , Resonancia por Plasmón de Superficie , Nanotecnología , Biomarcadores
4.
BMC Plant Biol ; 24(1): 698, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39044176

RESUMEN

Cold stress can impact plant biology at both the molecular and morphological levels. We cultivated two different types of tobacco seedlings using distinct seeding methods, observing significant differences in their cold tolerance at 4 °C. After 12 h cold stress, shallow water seeding cultivation treatment demonstrates a relatively good growth state with slight wilting of the leaves. Tobacco grown using the float system exhibited short, thick roots, while those cultivated through shallow water seeding had elongated roots with more tips and forks. After cold stress, the shallow water seeding cultivation treatment demonstrated higher antioxidant enzyme activity, and lower malondialdehyde (MDA) content.Transcriptome analysis was performed on the leaves of these tobacco seedlings at three stages of cold treatment (before cold stress, after cold stress, and after 3 days of recovery). Upon analyzing the raw data, we found that the shallow water seeding cultivation treatment was associated with significant functional enrichment of nicotinamide adenine dinucleotide (NAD) biosynthesis and NAD metabolism before cold stress, enrichment of functions related to the maintenance of cellular structure after cold stress, and substantial functional enrichment related to photosynthesis during the recovery period. Weighted gene co-expression network analysis (WGCNA) was conducted, identifying several hub genes that may contribute to the differences in cold tolerance between the two tobacco seedlings. Hub genes related to energy conversion were predominantly identified in shallow water seeding cultivation treatment during our analysis, surpassing findings in other areas. These include the AS gene, which controls the synthesis of NAD precursors, the PED1 gene, closely associated with fatty acid ß-oxidation, and the RROP1 gene, related to ATP production.Overall, our study provides a valuable theoretical basis for exploring improved methods of cultivating tobacco seedlings. Through transcriptome sequencing technology, we have elucidated the differences in gene expression in different tobacco seedlings at three time points, identifying key genes affecting cold tolerance in tobacco and providing possibilities for future gene editing.


Asunto(s)
Nicotiana , Plantones , Agua , Nicotiana/genética , Nicotiana/fisiología , Nicotiana/crecimiento & desarrollo , Plantones/genética , Plantones/crecimiento & desarrollo , Plantones/fisiología , Agua/metabolismo , Respuesta al Choque por Frío/genética , Respuesta al Choque por Frío/fisiología , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Frío
5.
Gastrointest Endosc ; 99(2): 177-185, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37500019

RESUMEN

BACKGROUND AND AIMS: Video analysis has emerged as a potential strategy for performance assessment and improvement. We aimed to develop a video-based skill assessment tool for peroral endoscopic myotomy (POEM). METHODS: POEM was deconstructed into basic procedural components through video analysis by an expert panel. A modified Delphi approach and 2 validation exercises were conducted to refine the POEM assessment tool (POEMAT). Twelve assessors used the final POEMAT version to grade 10 videos. Fully crossed generalizability (G) studies investigated the contributions of assessors, endoscopists' performance, and technical elements to reliability. G coefficients below .5 were considered unreliable, between .5 and .7 as modestly reliable, and above .7 as indicative of satisfactory reliability. RESULTS: After task deconstruction, discussions, and the modified Delphi process, the final POEMAT comprised 9 technical elements. G analysis showed low variance for endoscopist performance (.8%-24.9%) and high interrater variability (range, 63.2%-90.1%). The G score was moderately reliable (≥.60) for "submucosal tunneling" and "myotomy" and satisfactorily reliable (≥.70) for "active hemostasis" and "mucosal closure." CONCLUSIONS: We developed and established initial content and response process validity evidence for the POEMAT. Future steps include appraisal of the tool using a wider range of POEM videos to establish and improve the discriminative validity of this tool.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo , Acalasia del Esófago , Miotomía , Cirugía Endoscópica por Orificios Naturales , Humanos , Acalasia del Esófago/cirugía , Reproducibilidad de los Resultados , Resultado del Tratamiento , Esfínter Esofágico Inferior
6.
Gastrointest Endosc ; 99(6): 924-930, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38184116

RESUMEN

BACKGROUND AND AIMS: Opioid-induced esophageal dysfunction (OIED) often presents as spastic esophageal disorders (SEDs) and esophagogastric junction outflow obstruction (EGJOO). The aim of this study was to evaluate and compare clinical outcomes of peroral endoscopic myotomy (POEM) for SEDs and EGJOO among opioid users and nonusers. METHODS: This propensity score (PS) matching study included consecutive opioid users and nonusers who underwent POEM for SEDs and EGJOO between January 2018 and September 2022. The following covariates were used for the PS calculation: age, sex, duration of symptoms, Eckardt score, type of motility disorder, and length of myotomy during POEM. Clinical response was defined as a post-POEM Eckardt score ≤3. RESULTS: A total of 277 consecutive patients underwent POEM during the study period. PS matching resulted in the selection of 64 pairs of patients strictly matched 1:1 (n = 128) with no statistically significant differences in demographic, baseline, or procedural characteristics or in the parameters considered for the PS between the 2 groups. Clinical response to POEM was significantly lower among opioid users (51 of 64 [79.7%]) versus nonusers (60 of 64 [93.8%]) (P = .03) at a median follow-up of 18 months. Among opioid users, higher opioid dose (>60 morphine milligram equivalents per day) was associated with a higher likelihood of failure to respond to POEM (odds ratio, 4.59; 95% confidence interval, 1.31-3.98; P = .02). CONCLUSIONS: Clinical response to POEM for SEDs and EGJOO is significantly lower among opioid users versus nonusers. There was a dose-relationship between opioids and response to POEM, with higher daily opioid usage associated with a higher likelihood of treatment failure.


Asunto(s)
Trastornos de la Motilidad Esofágica , Miotomía , Puntaje de Propensión , Humanos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Trastornos de la Motilidad Esofágica/cirugía , Miotomía/métodos , Miotomía/efectos adversos , Analgésicos Opioides/uso terapéutico , Cirugía Endoscópica por Orificios Naturales/métodos , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Anciano , Estudios Retrospectivos , Resultado del Tratamiento , Trastornos Relacionados con Opioides/epidemiología , Esofagoscopía/métodos
7.
J Shoulder Elbow Surg ; 33(3): 628-639, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37981002

RESUMEN

BACKGROUND: The addition of epinephrine in irrigation fluid and the intravenous or local administration of tranexamic acid have independently been reported to decrease bleeding, thereby improving surgeons' visualization during arthroscopic shoulder procedures. No study has compared the effect of intravenous tranexamic acid, epinephrine in the irrigation fluid, or the combination of both tranexamic acid and epinephrine on visual clarity during shoulder arthroscopy with a placebo group. We hypothesized that intravenous tranexamic acid is more effective than epinephrine mixed in the irrigation fluid in improving visualization during shoulder arthroscopy, with no additive effect when both are used. METHODS: Patients aged ≥18 years undergoing shoulder arthroscopy were randomized into one of 4 study arms: (1) saline irrigation fluid (placebo); (2) epinephrine (0.33 mL of 1:1000 per liter) mixed in irrigation fluid (EPI); (3) 1 g intravenous tranexamic acid (TXA); and (4) epinephrine and tranexamic acid combined (TXA + EPI). Visualization was rated intraoperatively on a scale from 0, indicating poor clarity, to 3, indicating excellent clarity, every 15 minutes and overall. The primary outcome measure was the overall rating of visualization. A stepwise linear regression was performed using visualization as the dependent variable and independent variables including presence or absence of epinephrine and tranexamic acid, surgery duration, complexity, mean arterial pressure, increase in pump pressure, and volume of irrigation fluid. RESULTS: One hundred twenty-eight patients (mean age 56 years) were randomized. Mean visual clarity for the placebo, TXA, EPI, and TXA + EPI groups were 2.0 (±0.6), 2.0 (±0.6), 2.6 (±0.5), and 2.7 (±0.5), respectively (P < .001). The presence or absence of epinephrine was the most significant predictor of visual clarity (P < .001). Tranexamic acid presence or absence had no effect. No adverse events were recorded in any of the groups. CONCLUSION: Intravenous tranexamic acid is not an effective alternative to epinephrine in irrigation fluid to improve visualization during routine arthroscopic shoulder surgeries, and there is no additive effect when both are used.


Asunto(s)
Antifibrinolíticos , Articulación del Hombro , Ácido Tranexámico , Humanos , Adolescente , Adulto , Persona de Mediana Edad , Hombro/cirugía , Ácido Tranexámico/uso terapéutico , Artroscopía/métodos , Epinefrina , Articulación del Hombro/cirugía , Antifibrinolíticos/uso terapéutico , Pérdida de Sangre Quirúrgica/prevención & control , Método Doble Ciego
8.
Glob Chang Biol ; 29(10): 2655-2668, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36794561

RESUMEN

Numerous insects including pests and beneficial species undertake windborne migrations over hundreds of kilometers. In East Asia, climate-induced changes in large-scale atmospheric circulation systems are affecting wind-fields and precipitation zones and these, in turn, are changing migration patterns. We examined the consequences in a serious rice pest, the brown planthopper (BPH, Nilaparvata lugens) in East China. BPH cannot overwinter in temperate East Asia, and infestations there are initiated by several waves of windborne spring or summer migrants originating from tropical areas in Indochina. The East Asian summer monsoon, characterized by abundant rainfall and southerly winds, is of critical importance for these northward movements. We analyzed a 42-year dataset of meteorological parameters and catches of BPH from a standardized network of 341 light-traps in South and East China. We show that south of the Yangtze River during summer, southwesterly winds have weakened and rainfall increased, while the summer precipitation has decreased further north on the Jianghuai Plain. Together, these changes have resulted in shorter migratory journeys for BPH leaving South China. As a result, pest outbreaks of BPH in the key rice-growing area of the Lower Yangtze River Valley (LYRV) have declined since 2001. We show that these changes to the East Asian summer monsoon weather parameters are driven by shifts in the position and intensity of the Western Pacific subtropical high (WPSH) system that have occurred during the last 20 years. As a result, the relationship between WPSH intensity and BPH immigration that was previously used to predict the size of the immigration to the LYRV has now broken down. Our results demonstrate that migration patterns of a serious rice pest have shifted in response to the climate-induced changes in precipitation and wind pattern, with significant consequences for the population management of migratory pests.


Asunto(s)
Hemípteros , Oryza , Tiempo (Meteorología) , China , Animales
9.
J Org Chem ; 88(4): 2334-2343, 2023 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-36709459

RESUMEN

Herein, we report a palladium-catalyzed C(sp2)-H di- or monoarylation of short peptides containing N-terminal benzamide groups using aspartic acid (Asp) as an endogenous directing group. This strategy has the following merits: a broad substrate scope, selective diarylation of peptides, and gram-scale synthesis. Furthermore, this strategy can be successfully utilized to synthesize peptide-peptide conjugates.


Asunto(s)
Ácido Aspártico , Paladio , Catálisis , Péptidos
10.
BMC Pediatr ; 23(1): 602, 2023 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-38017394

RESUMEN

The objective of this study was to evaluate intraobserver reliability and inter-observer reproducibility of a 3-dimensional (3D) assessment method for mandibular changes of growing patients after orthodontic treatment for Class III malocclusion.Methods Cone-beam computed tomography (CBCT) scans were performed before and after orthodontic treatment for 27 patients. During the scan, the patient was positioned such that his/her mandibular plane was parallel to floor. Three observers independently worked on the DICOM data, reconstructed the pre- and post-treatment 3D models in software, selected the stable anatomical structures (basal bone area from the lingual surface of the symphysis to the distal aspect of the first molars) to guide the automated superimposition process. Then, each observer registered 14 anatomical landmarks on the virtual models, for three times after suitable interval, to generate 3 sets of coordinates; the mean was taken as the coordinates for that particular landmark. The intraobserver reliability and inter-observer reproducibility of the method were analyzed.Results The ICCs was > 0.90 for 25 (92.6%) of the intraobserver assessments. The precision of the measurement method was < 0.3 mm in 24 (88.9%) cases. The interobserver reproducibility errors were < 0.3 mm in 21 of the 27 cases.Conclusions The intraobserver reliability and inter-observer reproducibility of 3D assessment of mandibular changes using the virtual models were excellent.


Asunto(s)
Tomografía Computarizada de Haz Cónico Espiral , Humanos , Femenino , Masculino , Reproducibilidad de los Resultados , Imagenología Tridimensional/métodos , Mandíbula/diagnóstico por imagen , Tomografía Computarizada de Haz Cónico/métodos , Cefalometría
11.
J Hand Surg Am ; 48(10): 1059.e1-1059.e9, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-35545488

RESUMEN

PURPOSE: Current teaching suggests that modified Mason type III and IV fractures of the radial head involving more than 3 fragments should be treated with radial head arthroplasty. The purpose of this study was to compare the outcome of simple (2 or fewer intra-articular pieces) versus comminuted (3 or more intra-articular pieces) radial head fractures treated with open reduction internal fixation (ORIF). METHODS: This was a retrospective review of 35 patients with modified Mason type III and IV fractures treated with ORIF. For the purpose of our study, simple fractures were defined as having 2 or fewer intra-articular fragments. Comminuted fractures were defined as having 3 or more intra-articular fragments. The primary outcomes were Broberg and Morrey rating system and Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) scores. Reoperation rates and complications were also noted. RESULTS: Thirty-five patients were evaluated, with a mean follow-up of 39.3 months. Thirteen patients had radial head fractures consisting of 2 or fewer intra-articular fragments. Twenty-two patients had radial head fractures consisting of 3 or more intra-articular fragments. Ages and follow-up times were similar in the 2 groups. Similar QuickDASH and Broberg and Morrey scores were seen when evaluating subgroups of 2, 3, and 4 fragment fractures. One patient from each group underwent revision surgery for symptomatic hardware. CONCLUSIONS: In our series, we found similar clinical outcome scores and reoperation rates between simple and comminuted radial head fractures treated with ORIF. Fractures with more than 3 intra-articular fragments can be considered for ORIF. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.


Asunto(s)
Articulación del Codo , Fracturas Conminutas , Fracturas Radiales de Cabeza y Cuello , Fracturas del Radio , Humanos , Fracturas Conminutas/cirugía , Resultado del Tratamiento , Fijación Interna de Fracturas , Fracturas del Radio/cirugía , Articulación del Codo/cirugía , Estudios Retrospectivos , Rango del Movimiento Articular
12.
J Hand Surg Am ; 2023 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-37436341

RESUMEN

PURPOSE: Ulnar shortening osteotomy (USO) is commonly performed to alleviate pathologies causing ulnar-sided wrist pain. Surgical complications include nonunion and hardware removal, with rates up to 18% and 45%, respectively. The primary objective of the study was to report the overall complication rate of USO. The secondary objective was to identify risk factors for complications. METHODS: A retrospective multicenter cohort review was undertaken, including six Canadian cities over a 6-year period (January 2013-December 2018). Chart review was used to collect demographic data, surgical technique, implant used, and postoperative complications. Descriptive statistics of demographics and operative characteristics, including plate positioning, type of osteotomy, plate type, and ulnar variance (mm), were analyzed. Univariate analyses were used to select predictor variables for nonunion and hardware removal. These predictor variables were then entered into an adjusted multivariable logistic regression model. RESULTS: A total of 361 USOs were performed. Mean age was 46 ± 16 years (60.7% men). The overall complication rate was 37.1%, hardware removal rate was 29.6%, and nonunion rate was 9.4%. There was a workers' compensation claim associated with 21.6% of all complications, and it was a risk factor for both hardware removal (odds ratio [OR] = 3.81) and nonunion (OR = 2.88). Neither smoking nor diabetes was associated with complication rates. Seventy percent of plates were placed volarly, 25.5% dorsally, and 3.9% directly ulnar. Osteotomies were oblique in 83.7% of cases and transverse in 15.5%. Adjusted multivariate regression analysis revealed that younger age (OR = 0.98) was a risk factor for hardware removal and male sex (OR = 2.49) was a risk factor for nonunion. A surgical factor associated with hardware removal was direct ulnar plate placement (OR = 9.93). No surgical factors were associated with nonunions. CONCLUSIONS: There are substantial rates of complications with USOs. Direct ulnar plate placement should be avoided. Patients should be thoroughly counseled on the risks of complications prior to proceeding with USO. LEVEL OF EVIDENCE: Therapeutic IV.

13.
Int J Mol Sci ; 24(1)2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36614217

RESUMEN

Silicosis is a refractory disease. Previous studies indicate that damaged alveolar epithelial cells act as a driver in pulmonary fibrosis. Our results show that epithelial cells that acquire the mesenchymal phenotype are associated with the pathogenesis of silicosis. c-Src kinase, a non-receptor tyrosine kinase, has been shown to be a positive regulator of organ fibrosis, but specific mechanisms remain unclear and rarely researched in silicosis. The activated Phosphatidylinositol-3 kinases/AKT(PI3K/AKT) pathway promotes fibrosis. We aimed to determine whether c-Src regulates fibrosis via the PI3K/AKT signaling pathway in the development of silicosis. C57/BL mice were intratracheally perfused with 10 mg silica suspension to establish a model of silicosis. In vivo, silica particles induced lung fibrosis. The profibrotic cytokine transforming growth factor-ß1 (TGF-ß1) exhibited a high expression in pulmonary fibrosis. The phosphorylated c-Src protein was increased and the PI3K/AKT pathway was activated in model lung tissue. In vitro, silica increased the expression of TGF-ß1- and TGF-ß1-induced mesenchymal phenotype and fibrosis in a mouse epithelial cells line. siRNA-Src inhibited the c-Src, the phosphorylation of the PI3K/AKT pathway, and the mesenchymal phenotype induced by TGF-ß1. LY294002, a specific inhibitor of PI3K, suppressed the phosphorylation of PI3K/AKT but did not affect Src activation. SU6656, a selective Src inhibitor, attenuated fibrosis in silicosis model. In summary, c-Src promotes fibrosis via the PI3K/AKT pathway in silica-induced lung fibrosis, and Src kinase inhibitors are potentially effective for silicosis treatment.


Asunto(s)
Fibrosis Pulmonar , Silicosis , Ratones , Animales , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Dióxido de Silicio/toxicidad , Familia-src Quinasas/metabolismo , Silicosis/tratamiento farmacológico
14.
J Synchrotron Radiat ; 29(Pt 3): 775-786, 2022 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-35511010

RESUMEN

The structure and mechanical properties of the stomatopod dactyl club have been studied extensively for its extreme impact tolerance, but a systematic in situ investigation on the multiscale mechanical responses under high-speed impact has not been reported. Here the full dynamic deformation and crack evolution process within projectile-impacted dactyl using combined fast 2D X-ray imaging and high-resolution ex situ tomography are revealed. The results show that hydration states can lead to significantly different toughening mechanisms inside dactyl under dynamic loading. A previously unreported 3D interlocking structural design in the impact surface and impact region is reported using nano X-ray tomography. Experimental results and dynamic finite-element modeling suggest this unique structure plays an important role in resisting catastrophic structural damage and hindering crack propagation. This work is a contribution to understanding the key toughening strategies of biological materials and provides valuable information for biomimetic manufacturing of impact-resistant materials in general.


Asunto(s)
Crustáceos , Pezuñas y Garras , Tomografía Computarizada por Rayos X , Animales , Fenómenos Biomecánicos , Crustáceos/anatomía & histología , Crustáceos/fisiología , Pezuñas y Garras/anatomía & histología , Pezuñas y Garras/diagnóstico por imagen , Pezuñas y Garras/fisiología , Fenómenos Mecánicos , Estrés Mecánico
15.
Nat Mater ; 20(3): 395-402, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33257794

RESUMEN

Natural oxidases mainly rely on cofactors and well-arranged amino acid residues for catalysing electron-transfer reactions but suffer from non-recovery of their activity upon externally induced protein unfolding. However, it remains unknown whether residues at the active site can catalyse similar reactions in the absence of the cofactor. Here, we describe a series of self-assembling, histidine-rich peptides, as short as a dipeptide, with catalytic function similar to that of haem-dependent peroxidases. The histidine residues of the peptide chains form periodic arrays that are able to catalyse H2O2 reduction reactions efficiently through the formation of reactive ternary complex intermediates. The supramolecular catalyst exhibiting the highest activity could be switched between inactive and active states without loss of activity for ten cycles of heating/cooling or acidification/neutralization treatments, demonstrating the reversible assembly/disassembly of the active residues. These findings may aid the design of advanced biomimetic catalytic materials and provide a model for primitive cofactor-free enzymes.


Asunto(s)
Materiales Biomiméticos/química , Nanoestructuras/química , Oxidorreductasas/química , Péptidos/química , Catálisis , Dicroismo Circular , Coenzimas , Cristalografía por Rayos X , Histidina/química , Peroxidasa de Rábano Silvestre/química , Peroxidasa de Rábano Silvestre/metabolismo , Peróxido de Hidrógeno/química , Modelos Moleculares , Oxidación-Reducción , Oxidorreductasas/metabolismo , Conformación Proteica , Relación Estructura-Actividad Cuantitativa , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos X
16.
Surg Endosc ; 36(1): 402-412, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-33492500

RESUMEN

BACKGROUND AND AIMS: Esophageal stricture is a distressing issue for patients with early esophageal cancer following extensive endoscopic submucosal dissection (ESD), and the current steroid-based approaches are unsatisfactory for stricture prophylaxis. We evaluated the efficacy of oral hydrocortisone sodium succinate and aluminum phosphate gel (OHA) for stricture prophylaxis after extensive ESD. METHODS: Patients undergoing > 3/4 circumferential ESD were randomized to either the endoscopic loco-regional triamcinolone acetonide injection (ETI) plus oral prednisone group or the OHA group. The primary endpoint was incidence of esophageal stricture, and the secondary endpoints included adverse events (AEs) and endoscopic balloon dilations (EBDs). RESULTS: The incidence of esophageal stricture in OHA group (per-protocol analysis, 9.4%, 3/32; intention-to-treat analysis, 12.1%, 4/33) was significantly less than that of control group (per-protocol analysis, 35.5%, 11/31, P = 0.013; intention-to-treat analysis, 39.4%, 13/33, P = 0.011). Two sessions of EBD were necessary to release all strictures in the OHA group, while the similar EBDs (median 2, range 1-4) for 11 of the control. Operation-related AEs included infection (control vs. OHA group = 9.7% vs. 31.3%, P = 0.034), operation-related hypokalemia (19.4% vs. 31.3%, P = 0.278), perforation (3.2% vs. 3.1%), post-ESD hemorrhage (6.5% vs. 0%), and cardiac arrhythmia (0% vs. 6.3%). Steroid-related AEs included steroid-related hypokalemia (16.1% vs. 25%) and bone fracture (3.2% vs. 0%). Multivariate logistic regression analysis demonstrated that OHA was an independent protective factor for stricture (OR 0.079; 95%CI 0.011, 0.544; P = 0.01) and mucosal defect > 11/12 circumference was an independent risk factor (OR 49.91; 95%CI 6.7, 371.83; P < 0.001). CONCLUSIONS: OHA showed significantly better efficacy in preventing esophageal stricture after > 3/4 circumferential ESD compared to ETI plus oral prednisone.


Asunto(s)
Resección Endoscópica de la Mucosa , Neoplasias Esofágicas , Estenosis Esofágica , Resección Endoscópica de la Mucosa/efectos adversos , Neoplasias Esofágicas/complicaciones , Estenosis Esofágica/etiología , Estenosis Esofágica/prevención & control , Humanos , Esteroides , Triamcinolona
17.
J Chem Phys ; 157(8): 085103, 2022 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-36050012

RESUMEN

Lipid peroxides result from a reaction between cis-unsaturated lipid chains and singlet oxygen molecules leading to the addition of a peroxide OOH side group next to the acyl-chain double bond. It is now established that HP-POPC (hydroperoxidized POPC) molecules form stable, thin, and laterally expanded bilayers. The difference in the structural organization arises from the hydrophilic character of the OOH side group that has a strong affinity with the water interface region, leading to significant reorganization of the bilayer. In this article, we describe a coarse-grained (CG) model of POPC and DOPC lipid peroxides within the framework of the Martini CG force-field (v2.2), derived from experimental data. We then discuss extensively the predicted structure and the influence of hydration and show how shifting the position of the unsaturated bonds along the chain changes the structure. Finally, we provide electron and neutron scattering length density profiles of the simulated bilayers.


Asunto(s)
Membrana Dobles de Lípidos , Fosfolípidos , Interacciones Hidrofóbicas e Hidrofílicas , Membrana Dobles de Lípidos/química , Peróxidos Lipídicos , Fosfatidilcolinas/química , Fosfolípidos/química , Agua
18.
Arthroscopy ; 38(2): 315-322, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34329701

RESUMEN

PURPOSE: The purpose of this study was to investigate outcomes following arthroscopic elbow contracture release to describe the use of arthroscopy for improvement in extension/flexion and pronation/supination arcs of motion at a single institution for degenerative and posttraumatic etiologies. METHODS: Consecutive arthroscopic elbow arthrolysis performed between 2003 and 2015 were retrospectively reviewed. Basic patient demographics, indications for surgery, preoperative and postoperative elbow range of motion, postoperative patient outcome score, and all complications were recorded and analyzed. RESULTS: Fifty-two patients were included with an average follow-up of 5.1 years (range 1.4 to 9.4). Severe contractures made up 50% of cases, followed by 23% moderate, and 27% mild. Average extension/flexion for the post-traumatic group (n = 30) increased by 63° ± 31 and by 29° ± 24 for the degenerative group (n = 22). Average gain in pronosupination was 38° ± 62 in the post-traumatic group and 13°±23 in the degenerative group. Postoperative DASH scores were 17.5 ± 18.4 for post-traumatic cases and 12.8 ± 19.3 for degenerative cases. CONCLUSION: Arthroscopic elbow contracture release is an effective intervention for degenerative and post-traumatic elbow contracture for both flexion/extension and pronosupination contracture. Furthermore, a two-stage release should be considered when both flexion and pronosupinaton contractures are present. LEVEL OF EVIDENCE: IV, case series, treatment study.


Asunto(s)
Contractura , Articulación del Codo , Artroscopía/efectos adversos , Contractura/etiología , Contractura/cirugía , Codo , Articulación del Codo/cirugía , Humanos , Rango del Movimiento Articular , Estudios Retrospectivos , Resultado del Tratamiento
19.
J Shoulder Elbow Surg ; 31(3): 501-508, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34695593

RESUMEN

BACKGROUND: There is no consensus on the management of the radial head in total elbow arthroplasty (TEA). In 3-part TEA designs, options include radial head retention, excision, or arthroplasty. Biomechanical studies suggest improved varus-valgus stability with radial head implants in unlinked total elbows. Unfortunately, complications with radial head implants have been common with historical designs. The aim of this study was to evaluate the clinical and radiographic outcomes of radial head implants in a current 3-part TEA and identify risk factors for mechanical failure. METHODS: We performed a retrospective review of radial head implants with a 3-part convertible TEA from 2001 to 2016. Clinical outcomes, functional scores, and radiographic outcomes were recorded. The preoperative radiocapitellar alignment was measured using the radiocapitellar ratio (RCR). Statistics include descriptive statistics, t tests, logistic regression, and Kaplan-Meier survival curves. RESULTS: We identified 44 TEAs in 40 patients, with a mean follow-up period of 7.2 years. The average age at surgery was 58 ± 11 years; 80% of the TEAs were performed in women. The indication for surgery was rheumatoid arthritis in 86%; of the implants, 61% were unlinked. The average preoperative RCR was 10.7 ± 17.9. Postoperatively, 2 radial head implants (5%) were subluxated, 6 (14%) were dissociated, and 2 (5%) were dissociated with implant dislocation on radiographic review. The revision rate for radial head subluxation, dissociation, or dislocation was 7% (n = 3). Univariate logistic regression showed that male sex (P = .002), abnormal preoperative RCR (P = .02), linked implant (P = .03), and older age (P = .04) were risk factors for radial head subluxation, dissociation, or implant dislocation. A multivariate model with all 4 variables did not demonstrate statistical significance. CONCLUSION: The incidence of radial head arthroplasty subluxation, dissociation, or implant dislocation was high (23%). In a univariate logistic regression model, male sex, abnormal preoperative RCR, and linked implants were all statistically significant risk factors for mechanical failure of the radial head implant. Our multivariate model did not show any statistically significant independent risk factors. Polyethylene wear or loosening of the radial head implants was not observed in this study; failure of the bipolar linkage was the principal mode of failure. Although further study is required, caution should be used when considering inserting a radial head implant in male patients with significant preoperative radiocapitellar malalignment. Radial head subluxation or dissociation is not an absolute indication for revision in an asymptomatic patient. Improvements in radial head implant designs in TEA are needed.


Asunto(s)
Artroplastia de Reemplazo de Codo , Artroplastia de Reemplazo , Articulación del Codo , Artroplastia de Reemplazo de Codo/efectos adversos , Codo/cirugía , Articulación del Codo/diagnóstico por imagen , Articulación del Codo/cirugía , Femenino , Humanos , Masculino , Radio (Anatomía)/diagnóstico por imagen , Radio (Anatomía)/cirugía , Rango del Movimiento Articular , Resultado del Tratamiento
20.
Sensors (Basel) ; 22(18)2022 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-36146078

RESUMEN

Servers are the infrastructure of enterprise applications, and improving server performance under fixed hardware resources is an important issue. Conducting performance tuning at the application layer is common, but it is not systematic and requires prior knowledge of the running application. Some works performed tuning by dynamically adjusting the hardware prefetching configuration with a predictive model. Similarly, we design a BIOS (Basic Input/Output System)-based dynamic tuning framework for a Taishan 2280 server, including dynamic identification and static optimization. We simulate five workload scenarios (CPU-instance, etc.) with benchmark tools and perform scenario recognition dynamically with performance monitor counters (PMCs). The adjustable configurations provided by Kunpeng processing reach 2N(N>100). Therefore, we propose a joint BIOS optimization algorithm using a deep Q-network. Configuration optimization is modeled as a Markov decision process starting from a feasible solution and optimizing gradually. To improve the continuous optimization capabilities, the neighborhood search method of state machine control is added. To assess its performance, we compare our algorithm with the genetic algorithm and particle swarm optimization. Our algorithm shows that it can also improve performance up to 1.10× compared to experience configuration and perform better in reducing the probability of server downtime. The dynamic tuning framework in this paper is extensible, can be trained to adapt to different scenarios, and is more suitable for servers with many adjustable configurations. Compared with the heuristic intelligent search algorithm, the proposed joint BIOS optimization algorithm can generate fewer infeasible solutions and is not easily disturbed by initialization.


Asunto(s)
Algoritmos , Computadores , Cadenas de Markov
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