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1.
Nat Chem Biol ; 20(7): 835-846, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38287154

RESUMEN

Synchronized ferroptosis contributes to nephron loss in acute kidney injury (AKI). However, the propagation signals and the underlying mechanisms of the synchronized ferroptosis for renal tubular injury remain unresolved. Here we report that platelet-activating factor (PAF) and PAF-like phospholipids (PAF-LPLs) mediated synchronized ferroptosis and contributed to AKI. The emergence of PAF and PAF-LPLs in ferroptosis caused the instability of biomembranes and signaled the cell death of neighboring cells. This cascade could be suppressed by PAF-acetylhydrolase (II) (PAFAH2) or by addition of antibodies against PAF. Genetic knockout or pharmacological inhibition of PAFAH2 increased PAF production, augmented synchronized ferroptosis and exacerbated ischemia/reperfusion (I/R)-induced AKI. Notably, intravenous administration of wild-type PAFAH2 protein, but not its enzymatically inactive mutants, prevented synchronized tubular cell death, nephron loss and AKI. Our findings offer an insight into the mechanisms of synchronized ferroptosis and suggest a possibility for the preventive intervention of AKI.


Asunto(s)
Lesión Renal Aguda , Ferroptosis , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Lesión Renal Aguda/tratamiento farmacológico , Ferroptosis/efectos de los fármacos , Animales , Ratones , Ratones Endogámicos C57BL , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Factor de Activación Plaquetaria/metabolismo , Ratones Noqueados , Humanos , Masculino
2.
Langmuir ; 40(22): 11817-11827, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38760325

RESUMEN

Improving the dispersibility and compatibility of nanomaterials in water-borne epoxy resins is an important means to improve the protection ability and corrosion resistance of coatings. In this study, glycine-functionalized Ti3C2Tx (GT) was used to prepare an epoxy composite coating. The results of Fourier transform infrared spectroscopy and X-ray diffraction showed that glycine was successfully modified. The scanning electron microscopy and transmission electron microscopy results showed that the aggregation of Ti3C2Tx was alleviated. Electrochemical impedance spectroscopy test results show that, after 60 days of immersion, GT coating still shows the best protection performance, and the composite coating |Z|f = 0.01 Hz is 3 orders of magnitude higher than that of the pure epoxy coating. This is mainly because, after adding glycine, the -COOH group on the surface of glycine binds to the -OH group on the surface of Ti3C2Tx, improving the aggregation of Ti3C2Tx itself. At the same time, the -NH group of glycine can also participate in the curing reaction of epoxy resin to strengthen the bonding strength between the coating and the metal. The good dispersion of GT in epoxy resin makes it fill the pores and holes left by epoxy resin curing and strengthen the corrosion resistance. The easy availability and green properties of glycine provide a simple and environmentally friendly method for the modification of Ti3C2Tx.

3.
J Am Chem Soc ; 144(14): 6208-6214, 2022 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-35357829

RESUMEN

Here, we report on a new kind of compound, XδIr4X12-δ (X = P, As), the first hole-doped skutterudites superconductor. We provide atomic-resolution images of the caging As atoms using scanning transmission electron microscopy (STEM). By inserting As atoms into the caged structure under a high pressure, superconductivity emerges with a maximum transition temperature (Tc) of 4.4 K (4.8 K) in IrAs3 (IrP3). In contrast to all of the electron-doped skutterudites, the electronic states around the Fermi level in XδIr4X12-δ are dominated by the caged X atom, which can be described by a simple body-centered tight-binding model, implying a distinct pairing mechanism. Our density functional theory (DFT) calculations reveal an intimate relationship between the pressure-dependent local-phonon mode and the enhancement of Tc. The discovery of XδIr4X12-δ provides an arena to investigate the uncharted territory of hole-doped skutterudites, and the method proposed here represents a new strategy of carrier doping in caged structures, without introducing extra elements.

4.
Clin Genet ; 101(1): 101-109, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34671977

RESUMEN

Emerging evidence demonstrates the clinical utility of genomic applications in newborn intensive care unit (NICU) patients with strong indications of Mendelian etiology. However, such applications' diagnostic yield and utility remain unclear for NICU cohorts with minimal phenotype selection. In this study, focused medical exome sequencing was used as a first-tier, singleton-focused diagnostic tool for 2303 unrelated sick neonates. Integrated analysis of single nucleotide variants (SNVs), small insertions and deletions (Indels), and large copy number variants (CNVs) was performed. The diagnostic rate in this NICU cohort is 12.3% (284/2303), with 190 probands with molecular diagnoses made from SNV/Indel analyses (66.9%), 93 patients with diagnostic aneuploidy/CNVs findings (32.8%), and 1 patient with both SNV and CNV (0.4%). In addition, 54 (2.3%) of patients had a reportable incidental finding. Multiple organ involvements, craniofacial abnormalities, and dermatologic abnormalities were the strongest positive predictors for a molecular diagnosis. Among the 190 cases with SNV/Indel defects, direct impacts on medical management were observed in 46.8% of patients after the results were reported. In this study, we demonstrate that focused medical exome sequencing is a powerful first-line diagnostic tool for NICU patients. Significant number of diagnosed NICU patients can benefit from more focused medical management and long-term care.


Asunto(s)
Secuenciación del Exoma , Estudios de Asociación Genética , Enfermedades Genéticas Congénitas/diagnóstico , Enfermedades Genéticas Congénitas/genética , Predisposición Genética a la Enfermedad , Unidades de Cuidado Intensivo Neonatal , Alelos , China , Mapeo Cromosómico , Variaciones en el Número de Copia de ADN , Femenino , Estudios de Asociación Genética/métodos , Pruebas Genéticas , Humanos , Mutación INDEL , Masculino , Polimorfismo de Nucleótido Simple , Secuenciación Completa del Genoma
5.
BMC Cancer ; 22(1): 1154, 2022 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-36348289

RESUMEN

BACKGROUND: The prognosis of patients with gastric cancer (GC) with gastric outlet obstruction (GOO) after gastrectomy is highly variable. In this study, we aimed to develop a nomogram to predict the prognosis of these patients. PATIENTS AND METHODS: Data from 218 GC patients with GOO who underwent gastrectomy at Sun Yat-sen University Cancer Center were retrospectively collected as a training cohort. The data of 59 patients with the same diagnosis who underwent gastrectomy at the First Affiliated Hospital of Guangxi Medical University were collected as an external verification cohort. A nomogram for the overall survival (OS) was developed using the Cox regression model in the training cohort, which was validated in a verification cohort. RESULTS: Multivariate analysis showed that the surgical procedure (P < 0.001), period of chemotherapy (P < 0.001), T stage (P = 0.006), N stage (P = 0.040), systemic immune-inflammatory index (SII) (P < 0.001), and fibrinogen level (P = 0.026) were independent factors affecting OS. The nomogram constructed on the aforementioned factors for predicting the 1- and 3-year OS achieved a Harrell's concordance index (C-index) of 0.756 and 0.763 for the training and verification cohorts, respectively. Compared with the 8th American Joint Committee on Cancer (AJCC) Tumour-Node-Metastasis (TNM) staging system, the nomogram had higher C-index values and areas under the curve (AUCs) and slightly higher net clinical benefit. CONCLUSION: Compared to the 8th AJCC staging system, the newly developed nomogram showed superior performance in predicting the survival of GC patients with GOO after gastrectomy.


Asunto(s)
Obstrucción de la Salida Gástrica , Neoplasias Gástricas , Humanos , Nomogramas , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/cirugía , Estudios Retrospectivos , China/epidemiología , Pronóstico , Obstrucción de la Salida Gástrica/etiología , Obstrucción de la Salida Gástrica/cirugía , Estadificación de Neoplasias
6.
J Am Chem Soc ; 143(18): 7042-7049, 2021 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-33926192

RESUMEN

The charge, spin, and composition degrees of freedom in a high-entropy alloy endow it with tunable valence and spin states, infinite combinations, and excellent mechanical performance. Meanwhile, the stacking, interlayer, and angle degrees of freedom in a van der Waals material bring to it exceptional features and technological applications. Integration of these two distinct material categories while keeping their merits would be tempting. On the basis of this heuristic thinking, we design and explore a new range of materials (i.e., dichalcogenides, halides, and phosphorus trisulfides) with multiple metallic constitutions and intrinsic layered structure, which are coined as high-entropy van der Waals materials. Millimeter-scale single crystals with a homogeneous element distribution can be efficiently acquired and easily exfoliated or intercalated in this materials category. Multifarious physical properties such as superconductivity, magnetic ordering, metal-insulator transition, and corrosion resistance have been exploited. Further research based on the concept of high-entropy van der Waals materials will enrich the high-throughput design of new systems with intriguing properties and practical applications.

7.
Small ; 17(29): e2101180, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34145754

RESUMEN

Photodynamic therapy (PDT), which utilizes photosensitizer to convert molecular oxygen into singlet oxygen (1 O2 ) upon laser irradiation to ablate tumors, will exacerbate the already oxygen shortage of most solid tumors and is thus self-limiting. Herein, a sophisticated photosensitive polymeric material (An-NP) that allows sustained 1 O2 generation and sufficient oxygen supply during the entire phototherapy is engineered by alternatively applying PDT and photothermal therapy (PTT) controlled by two NIR laser beams. In addition to a photosensitizer that generates 1 O2 , An-NP consists of two other key components: a molecularly designed anthracene derivative capable of trapping/releasing 1 O2 with superior reversibility and a dye J-aggregate with superb photothermal performance. Thus, in 655 nm laser-triggered PDT process, An-NP generates abundant 1 O2 with extra 1 O2 being trapped via the conversion into EPO-NP; while in the subsequent 785 nm laser-driven PTT process, the converted EPO-NP undergoes thermolysis to liberate the captured 1 O2 and regenerates An-NP. The intratumoral oxygen level can be replenished during the PTT cycle for the next round of PDT to generate 1 O2 . The working principle and phototherapy efficacy are preliminarily demonstrated in living cells and tumor-bearing mice, respectively.


Asunto(s)
Fotoquimioterapia , Oxígeno Singlete , Animales , Línea Celular Tumoral , Ratones , Fármacos Fotosensibilizantes/uso terapéutico , Fototerapia
9.
Anal Chem ; 92(15): 10792-10799, 2020 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-32648733

RESUMEN

Endowing fluorogenic probes with ultrahigh contrast is essential to increasing the accuracy of fluorescence sensing and imaging. Phenolate-based D-π-A fluorophores (A-DOH) belong to a big family of fluorophores and have attracted increasing attention in fluorogenic probe design. However, the intrinsic dilemma of weak intracellular emission of traditional A-DOH fluorophores resulted in low contrast during live cell imaging. Herein, we present a general and robust approach to preparing novel A-DOH fluorophores with bright NIR fluorescence in living cells based on the unique halogen effects. The reported chlorinated A-DOH fluorophore (A1-2ClOH) has an extremely strong fluorescence in an aqueous solution of pH 7.4 and living cells, which is 194 and 30 times higher than that of the traditional halogen-free analogue (A1-OH), respectively. We systematically investigated and demonstrated that the distinct -I and +M halogen effects, which led to a drastic decrease in the pKa value and a significant enhancement in the fluorescence quantum yield, respectively, should be responsible for the tremendous fluorescence enhancement. The flexible phenol caging chemistry allows one to prepare multiple NIR fluorogenic probes based on the A1-2ClOH scaffold with high contrast for live cell imaging of a variety of analytes by introducing a corresponding triggering moiety. Moreover, the conjugated azide group of A1-2ClOH enables the integration of more functions as desired through a facile click reaction. A fluorogenic probe (mitoProbe-PN) was synthesized as a paradigm by equipping the A1-2ClOH scaffold with a mitochondria-targeting moiety and a peroxynitrite-responsive triggering group and demonstrated specific high-contrast fluorescence imaging of endogenous OONO- in mitochondria of living macrophages.


Asunto(s)
Colorantes Fluorescentes/química , Halógenos/química , Rayos Infrarrojos , Línea Celular Tumoral , Colorantes Fluorescentes/metabolismo , Halógenos/metabolismo , Humanos , Mitocondrias/metabolismo , Ácido Peroxinitroso/química
10.
Chemistry ; 26(20): 4505-4509, 2020 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-32077546

RESUMEN

Dye assemblies exhibit fascinating properties and performances, both of which depend critically on the mutual packing arrangement of dyes and on the supramolecular architecture. Herein, we engineered, for the first time, an intriguing chlorosome-mimetic 2D crystalline J-dimer lamellar structure based on halogenated dyes in aqueous media by employing two distinct orthogonal halogen-bonding (XB) interactions. As the only building motif, antiparallel J-dimer was formed and stabilized by single π-stacking and dual halogen⋅⋅⋅π interactions. With two substituted halogen atoms acting as XB donors and the other two acting as acceptors, the constituent J-dimer units were linked by quadruple highly-directional halogen⋅⋅⋅halogen interactions in a staggered manner, resulting in unique 2D lamellar dye assemblies. This work champions and advances halogen-bonding as a remarkably potent tool for engineering dye aggregates with a controlled molecular packing arrangement and supramolecular architecture.

11.
World J Surg ; 44(5): 1666-1672, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31915978

RESUMEN

BACKGROUND: Blunt cardiac injury (BCI) increases with traffic accidents and is an important cause of death in trauma patients. In particular, for patients who need surgical treatment, the mortality rate is extremely high unless the patient is promptly operated on. This study aimed to explore early recognition and expeditious surgical intervention to increase survival. METHODS: All patients with BCIs during the past 15 years were reviewed, and those who underwent operative treatment were analyzed retrospectively regarding the mechanism of injury, diagnostic and therapeutic methods, and outcome. RESULTS: A total of 348 patients with BCIs accounted for 18.3% of 1903 patients with blunt thoracic injury (BTI). Of 348 patients, 43 underwent operative treatment. The main cause of injury was traffic accidents, with an incidence of 48.8%. Of them, steering wheel injuries occurred in 15 patients. In 26 patients, a preoperative diagnosis was obtained by echocardiography, CT scanning, etc. In the remaining 17, who had to undergo urgent thoracotomy without any preoperative imaging, a definitive diagnosis of BCI was proven during the operation. The volume of preoperative infusion or crystalloid was <1000 ml in 31 cases. Preoperative pericardiocentesis was not used in anyone. In 12 patients, the operation commenced within 1 h. Overall mortality was 32.6%. The death was caused by BCI in 9. CONCLUSIONS: Facing a patient with BTI, a high index of suspicion for BCI must be maintained. To manage those requiring operations, early recognition and expeditious thoracotomy are essential. Preoperatively, limited fluid resuscitation is emphasized. We do not advocate preoperative pericardiocentesis.


Asunto(s)
Lesiones Cardíacas/diagnóstico , Lesiones Cardíacas/cirugía , Heridas no Penetrantes/diagnóstico , Heridas no Penetrantes/cirugía , Accidentes de Tránsito , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ecocardiografía , Urgencias Médicas , Femenino , Lesiones Cardíacas/etiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Toracotomía , Factores de Tiempo , Tomografía Computarizada por Rayos X , Heridas no Penetrantes/etiología , Adulto Joven
12.
J Am Chem Soc ; 141(1): 402-413, 2019 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-30547576

RESUMEN

Controlling the packing arrangements of dyes is a facile way of tuning their photophysical and/or photochemical properties, thus enabling new sensing mechanisms for photofunctional tools. Here, we present a general and robust strategy toward water-stable J-aggregated dye-templated nanoassemblies by incorporating an amphiphilic diblock copolymer and a stimuli-responsive dye as the only two building components. An iodo-substituted boron dipyrromethene (BODIPY) was adopted as a template to direct the self-assembly of poly(ethylene glycol)- block-polycaprolactone (PEG-PCL), forming a core-shell nanoplate with slip-stacked BODIPYs as core surrounded by hydrophilic PEG shell. The self-assembled nanoplate is stable in cell culture medium and possesses a built-in stimuli-responsiveness that arises from BODIPY bearing meso-carboxylate protecting group, which is efficiently removed upon treatment with peroxynitrite. The resulting negative charges lead to rearrangement of dyes from J-stacking to nonstacking, which activates photoinduced singlet oxygen production from the nanoassemblies. The stimuli-activatable photosensitivity has been exploited for specific photodynamic ablation of activated RAW 264.7 cells with excessive endogenous peroxynitrite. In light of the generality of the sensing mechanism, the concept described herein will significantly expand the palette of design principles to develop diverse photofunctional tools for biological research and clinical needs.


Asunto(s)
Colorantes/química , Nanoestructuras/química , Compuestos de Boro/química , Interacciones Hidrofóbicas e Hidrofílicas , Lactonas/química , Modelos Moleculares , Conformación Molecular , Fármacos Fotosensibilizantes/química , Polietilenglicoles/química
13.
Angew Chem Int Ed Engl ; 58(46): 16601-16609, 2019 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-31469219

RESUMEN

Activatable photosensitizers (aPSs) sensitive to specific stimuli hold potential for targeting multiple disease biomarkers and are desirable for photodynamic therapy (PDT). Presented herein is the design of aPSs that can be activated and fully recover from an inhibited state in the presence of specific biomarker. A designed long-wavelength D-π-A photosensitizer, PSSe-I , with highly efficient photosensitivity for generation of 1 O2 was used. Caging of the phenolate donor of PSSe-I with a biomarker-sensitive group provided ALP PS, and the drastic activation of its photosensitivity was demonstrated intracellularly. To enhance the flexibility of the design strategy, a clickable azide group was introduced into the scaffold to allow integration of more functionality. Modularly derived mito-PN PS, equipped with a mitochondria-targeting group and a specific peroxynitrite-reactive trigger, was synthesized and demonstrated superior performance in cells. This strategy could lead to customization of aPSs applicable to a specific PDT.


Asunto(s)
Luz , Fármacos Fotosensibilizantes/química , Animales , Azidas/química , Biomarcadores/química , Supervivencia Celular/efectos de los fármacos , Fluoresceínas/química , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Ratones , Microscopía Fluorescente , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Ácido Peroxinitroso/química , Fármacos Fotosensibilizantes/farmacología , Células RAW 264.7 , Oxígeno Singlete/química , Oxígeno Singlete/metabolismo
14.
J Med Genet ; 54(10): 685-692, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28705883

RESUMEN

BACKGROUND: Copy number variation (CNV) is a valuable source of genetic diversity in the human genome and a well-recognised cause of various genetic diseases. However, CNVs have been considerably under-represented in population-based studies, particularly the Han Chinese which is the largest ethnic group in the world. OBJECTIVES: To build a representative CNV map for the Han Chinese population. METHODS: We conducted a genome-wide CNV study involving 451 male Han Chinese samples from 11 geographical regions encompassing 28 dialect groups, representing a less-biased panel compared with the currently available data. We detected CNVs by using 4.2M NimbleGen comparative genomic hybridisation array and whole-genome deep sequencing of 51 samples to optimise the filtering conditions in CNV discovery. RESULTS: A comprehensive Han Chinese CNV map was built based on a set of high-quality variants (positive predictive value >0.8, with sizes ranging from 369 bp to 4.16 Mb and a median of 5907 bp). The map consists of 4012 CNV regions (CNVRs), and more than half are novel to the 30 East Asian CNV Project and the 1000 Genomes Project Phase 3. We further identified 81 CNVRs specific to regional groups, which was indicative of the subpopulation structure within the Han Chinese population. CONCLUSIONS: Our data are complementary to public data sources, and the CNV map may facilitate in the identification of pathogenic CNVs and further biomedical research studies involving the Han Chinese population.


Asunto(s)
Pueblo Asiatico/genética , Variaciones en el Número de Copia de ADN , Etnicidad/genética , Variación Genética , Genoma Humano , China , Humanos , Masculino
15.
J Craniofac Surg ; 29(5): 1338-1340, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29608485

RESUMEN

OBJECTIVE: Spasmodic torticollis (ST) is an idiopathic neurologic disorder affecting the muscles of the neck. Surgery is a preferred treatment, when conservative treatments or Botulinum neurotoxin injections fail to relieve the symptoms. Our objective here is to report the outcome of a new surgical method for treating ST patients in our department. METHODS: The new procedure consists of rhizotomy of the spinal accessory nerve (SAN) and C1-C2 nerve roots, coagulation of the distal end of SAN (Group A). The results of this procedure were compared with a group of patients who underwent only rhizotomy of the SAN and anterior C1-C2 nerve roots (Group B). Clinical data were retrospectively collected from 39 patients with laterocollis and rotatory torticollis subtypes of ST from Jun 1, 2014 to Jun 1, 2015. The effect of the surgery was evaluated by the reduction in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total scores preoperatively and postoperatively. The mean duration of the postoperative follow-up period was 2.57 years, ranging from 2 to 3 years. RESULTS: The mean preoperative TWSTRS score was 65.89 ±â€Š3.55 and 65.80 ±â€Š3.45 in Groups A and B, respectively. Six months after the surgery, the TWSTRS scores decreased to 40.00 ±â€Š12.14 and 26.04 ±â€Š11.77, respectively. There was a statistically significant improvement preoperatively and postoperatively in both groups (P < 0.05). The decrease in TWSTRS score of Group B was more significant than that of Group A (P < 0.05). The main complications included shoulder numbness, shoulder weakness, and hoarseness. CONCLUSIONS: The procedure in this study provides a new and effective surgical method for patients with ST. This procedure should be recommended if conservative therapy does not offer satisfactory relief of symptoms.


Asunto(s)
Nervio Accesorio/cirugía , Electrocoagulación , Rizotomía/métodos , Raíces Nerviosas Espinales/cirugía , Tortícolis/cirugía , Adulto , Anciano , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
16.
Cell Tissue Bank ; 19(1): 35-46, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28815373

RESUMEN

Cell based tissue engineering serves as a promising strategy for articular cartilage repair, which remains a challenge both for researchers and clinicians. The aim of this research was to assess the potential of autologous nasal chondrocytes (NCs) combined with alginate hydrogel as injectable constructs for rabbit articular cartilage repair. Autologous nasal chondrocytes were isolated from rabbit nasal septum, expanded either on monolayer or in 3D alginate hydrogel. In vitro, DNA quantification revealed that NCs can proliferate stable in 3D alginate matrix, but slower than that cultured in monolayer. Further, a higher synthesis rate of glycosaminoglycans (GAGs) was detected by GAG measurement in 3D alginate culture. Gene expression analysis at different time point (day 1, 7, 14) showed that 3D culture of NCs in alginate up-regulated chondrogenic markers (Col2A1, ACAN SOX9), meanwhile down-regulated dedifferentiation related gene (Col1A1). In vivo, autologous nasal chondrocytes combined with alginate hydrogel were used for repairing rabbit knee osteochondral defect (Alg + NC group). Histological staining indicated that Alg + NC group obtained superior and more hyaline-like repaired tissue both at 3 and 6 months after surgery. Mechanical analysis showed that the repaired tissue in the Alg + NC group possessed similar mechanical properties to the native cartilage. In conclusion, nasal chondrocytes appeared to be a very promising seed cell source for cartilage tissue engineering, and alginate hydrogel can serve as suitable delivery system.


Asunto(s)
Cartílago Articular/fisiología , Condrocitos/trasplante , Hidrogeles/química , Tabique Nasal/citología , Regeneración , Andamios del Tejido/química , Alginatos/administración & dosificación , Animales , Cartílago Articular/citología , Separación Celular , Condrocitos/citología , Condrocitos/metabolismo , Condrogénesis , Ácido Glucurónico/administración & dosificación , Ácidos Hexurónicos/administración & dosificación , Hidrogeles/administración & dosificación , Inyecciones , Conejos , Ingeniería de Tejidos
17.
J Am Chem Soc ; 139(29): 10157-10163, 2017 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-28654288

RESUMEN

A general approach toward highly fluorogenic probes across the visible spectrum for various analytes offers significant potential for engineering a wide range of bioprobes with diverse sensing and imaging functions. Here we show a facile and general strategy that involves introducing a new fluorogenic mechanism in boron dipyrromethene (BODIPY) dyes, based on the principle of stimuli-triggered dramatic reduction in the electron-withdrawing capabilities of the meso-substituents of BODIPYs. The fluorogenic mechanism has been demonstrated to be applicable in various BODIPYs with emission maxima ranging from green to far red (509, 585, and 660 nm), and the synthetic strategy allows access to a panel of highly fluorogenic bioprobes for various biomolecules and enzymes (H2O2, H2S, and protease) via introducing specific triggering motifs. The potency of the general design strategy is exemplified by its application to develop a mitochondria-targeting far-red probe capable of imaging of endogenous H2O2 in living cells.


Asunto(s)
Técnicas Biosensibles , Compuestos de Boro/química , Colorantes Fluorescentes/química , Peróxido de Hidrógeno/análisis , Imagen Óptica , Péptido Hidrolasas/análisis , Porfobilinógeno/análogos & derivados , Compuestos de Boro/farmacología , Supervivencia Celular , Electrones , Colorantes Fluorescentes/farmacología , Células HeLa , Humanos , Mitocondrias/química , Mitocondrias/metabolismo , Estructura Molecular , Péptido Hidrolasas/metabolismo , Porfobilinógeno/química , Porfobilinógeno/farmacología , Espectrometría de Fluorescencia , Espectrofotometría Ultravioleta
18.
Arch Orthop Trauma Surg ; 136(2): 223-32, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26626056

RESUMEN

INTRODUCTION: The aim of this prospective study was to investigate the effect of local hip bone density on mechanical failure after fixation of pertrochanteric fractures and to establish possible risk factors for the failures. MATERIALS AND METHODS: A total of 136 consecutive patients presenting a closed unilateral pertrochanteric fracture were enrolled. The patients were treated with a sliding hip screw or an intramedullary nail. Dual energy X-ray absorptiometry measurements for bone density of the contralateral hip were made within 4 weeks postoperatively. Follow-up evaluations on the standard radiographs were documented for any mechanical failure including loss of reduction, screw or blade cut-out, lateral migration of the screw or blade, and implant breakage. Secondary outcomes were also recorded including patient characteristics and fixation construct variables as possible predictors for mechanical failure. RESULTS: At a minimum of 2 years of follow-up, 38 patients were reported with mechanical failure at an estimated risk of 27.9 %. The local bone density measurements for the study population showed no difference between patients with (0.710 g/cm(2)) and without (0.726 g/cm(2)) mechanical failure (P = 0.180). We also observed no significant correlation between local bone density and failure in patients with good fracture reduction (P = 0.862). The multivariate regression analysis identified fracture type (P < 0.001) and quality of fracture reduction (P < 0.001) as being independent predictors for mechanical failure, whereas local bone density was not (P = 0.658). CONCLUSIONS: Local hip bone density does not appear to have a significant influence on mechanical failure after internal fixation of pertrochanteric fractures. Stable fractures and fractures with good reduction are expected to obtain satisfactory outcomes.


Asunto(s)
Densidad Ósea , Fracturas del Fémur/cirugía , Fijación Interna de Fracturas/efectos adversos , Articulación de la Cadera/diagnóstico por imagen , Absorciometría de Fotón , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Insuficiencia del Tratamiento
19.
BMC Neurosci ; 15: 101, 2014 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-25160131

RESUMEN

BACKGROUND: The causes of dural arteriovenous fistula have not been clearly defined. The aim of this study was to investigate the mechanism of dural arteriovenous fistula formation induced by high intracranial venous pressure using a rabbit model. RESULTS: By using rabbit model, dural arteriovenous fistula formation induced by high intracranial venous pressure could be produced by end-to-end and end-to-side anastomosis of the right side common carotid artery with the posterior facial vein plus ligation of the contralateral external jugular vein. As compared the post arteriovenous fistula formation among 1 week, 2 weeks, 3 weeks, and 90 days, the expression level of vascular endothelial growth factor in the 1- and 2-weeks groups was significantly higher compared with the control group, 3 weeks and 90 days groups (p ≤ 0.002). There was significantly higher hypoxia inducible factor-1α expression in the one week group compared with the control, 2 weeks, 3 weeks, and 90 days groups (p ≤ 0.002). The results of Western blotting showed that vascular endothelial growth factor expression level was highest in the 1 week group. The expression level of vascular endothelial growth factor was significantly different between all groups. CONCLUSIONS: The results of the experiments in our rabbit model indicate that high intracranial venous pressure is a key for dural arteriovenous fistula formation. Cerebral ischemia caused by lack of cerebral perfusion pressure plays a key role in the process that leads from high intracranial venous pressure to increased hypoxia inducible factor-1α expression and then increased vascular endothelial growth factor expression.


Asunto(s)
Malformaciones Vasculares del Sistema Nervioso Central/etiología , Malformaciones Vasculares del Sistema Nervioso Central/fisiopatología , Trastornos Cerebrovasculares/complicaciones , Trastornos Cerebrovasculares/fisiopatología , Presión Venosa , Animales , Western Blotting , Isquemia Encefálica/complicaciones , Isquemia Encefálica/fisiopatología , Modelos Animales de Enfermedad , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Inmunohistoquímica , Masculino , Conejos , Distribución Aleatoria , Factores de Tiempo , Factor A de Crecimiento Endotelial Vascular/metabolismo
20.
ACS Omega ; 9(23): 25309-25321, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38882076

RESUMEN

Many mines in Guizhou Province are in urgent need of renovation to ensure harmonious operation and prolong their lifespan. The key to successful renovation lies in the prudent selection of the appropriate mining technologies. Therefore, a comprehensive investigation was conducted on steep coal mines in Guizhou Province, and a comprehensive evaluation framework was established. Spearman correlation analysis was performed on various factors, selecting geological conditions and working face parameters with high correlation as the input variables and mining methods as the output variables. The optimal values of each hyperparameter were determined through orthogonal experiments, and the neural network structure was confirmed to be "17-9-3". Five variants of backpropagation (BP) algorithms were meticulously tested, and a genetic algorithm optimizing the BP neural network (GA-BP) was further assessed to improve the model's prediction accuracy. The accuracy of the model was evaluated via the coefficient of determination (R 2) and mean squared error (MSE). The research results indicated that the variable step-size algorithm with a momentum term (VSS + MT) was the optimal algorithm for the BP neural network. Additionally, the MSE values of the artificial neural network and GA-BP neural network in the testing phase were 0.06 and 0.04, with prediction success rates of 70 and 90%, respectively, and R 2 values of 0.79 and 0.85, respectively. Thus, the GA-BP neural network demonstrated superior performance. Finally, industrial application of the model was conducted on a working face in the Zhong-Yu coal mine. The evaluation index for the working face was "0.847, 0.09, 0.111", suggesting that fully mechanized mining should be adopted. The evaluation results were consistent with the current production status of the mine, verifying the reliability of the model in practical applications.

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