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1.
J Sep Sci ; 47(4): e2300811, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38403440

RESUMEN

In this work, surface molecularly imprinted polymers based on magnetic multi-walled carbon nanotubes were prepared for the specific recognition and adsorption of resveratrol. The functionalization of magnetic multi-walled carbon nanotubes and the synthesis process of surface molecularly imprinted polymers were optimized. Characterizations were performed to demonstrate the successful synthesis of the imprinted materials. The imprinted materials showed satisfactory adsorption capacity of resveratrol (45.73 ± 1.72 mg/g) and excellent selectivity (imprinting factor 2.89 ± 0.15). In addition, the imprinted materials were used as adsorbents in molecularly imprinted solid-phase extraction for the purification of resveratrol from crude extracts of some food and medicinal resources, achieving recoveries of 93.69%-95.53% with high purities of 88.37%-92.33%. Moreover, the purified products exhibited extremely strong free radical scavenging activity compared with crude extracts. Overall, this work provided a promising approach for the highly selective purification of resveratrol from natural resources, which would contribute to the application of this valuable compound in the food/nutraceutical fields.


Asunto(s)
Fallopia japonica , Impresión Molecular , Nanotubos de Carbono , Vitis , Resveratrol , Polímeros Impresos Molecularmente , Arachis , Polímeros , Adsorción , Mezclas Complejas , Fenómenos Magnéticos , Extracción en Fase Sólida
2.
Phytomedicine ; 125: 155295, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38277945

RESUMEN

BACKGROUND: Geniposidic acid (GPA) alleviates oxidative stress and inflammation in mice However, whether it can effectively regulate lipid accumulation and prevent hyperlipidemia requires further investigation. PURPOSE: This study combined the untargeted metabolomics of cells and a Caenorhabditis elegans model to evaluate the anti-hyperlipidemic potential of GPA by modulating oxidative stress and regulating lipid metabolism. A golden hamster model of hyperlipidemia was used to further validate the lipid-lowering effect and mechanism of action of GPA. METHODS: Chemical staining, immunofluorescence, and flow cytometry were performed to examine the effects of GPA on lipid accumulation and oxidative stress. Untargeted metabolomic analysis of cells and C. elegans was performed using ultra-performance liquid chromatography coupled with quadrupole electrostatic field Orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap MS) to identify biomarkers altered by GPA action, analyze the affected metabolic pathways, and validate the mechanisms by which GPA regulates lipid metabolism and oxidative stress. A golden hamster model of hyperlipidemia was established to test the lipid-lowering effects of GPA. Body weight, biochemical markers, rate-limiting enzymes, and key proteins were assessed. Hematoxylin and eosin (H&E) and Oil Red O staining were performed. RESULTS: Phenotypic data showed that GPA decreased free fatty acid (FFA)-induced lipid buildup and high reactive oxygen species (ROS) levels, reversed the decrease in mitochondrial membrane potential (MMP), and increased the cellular reduced glutathione/oxidized glutathione disulfide (GSH/GSSG) ratio. GPA also reduces high glucose-induced lipid build-up and ROS production in C. elegans. Metabolomic analysis showed that GPA affected purine, lipid, and amino acid metabolism. Moreover, GPA inhibited xanthine oxidase (XOD), glutamate dehydrogenase (GLDH), fatty acid synthase (FAS), phosphorylation of P38 MAPK, and upregulated the expression of SIRT3 and CPT1A protein production to control lipid metabolism and produce antioxidant benefits in cells and golden hamsters. CONCLUSION: Current evidence suggests that GPA can effectively regulate lipid metabolism and the oxidative stress response, and has the potential to prevent hyperlipidemia. This study also provided an effective method for evaluating the mechanism of action of GPA.


Asunto(s)
Caenorhabditis elegans , Hiperlipidemias , Glucósidos Iridoides , Cricetinae , Animales , Ratones , Humanos , Caenorhabditis elegans/metabolismo , Células Hep G2 , Especies Reactivas de Oxígeno/metabolismo , Mesocricetus , Metabolómica , Hiperlipidemias/tratamiento farmacológico , Lípidos , Metabolismo de los Lípidos
3.
Sci Rep ; 13(1): 22978, 2023 12 27.
Artículo en Inglés | MEDLINE | ID: mdl-38151519

RESUMEN

To evaluate the clinical efficacy and meniscus healing rates of the arthroscopically assisted tendon graft fixation of the medial meniscus posterior root tears (MMPRTs), and to identify some independent risk factors correlated with meniscal root healing status. We conducted a retrospective study with 129 patients who received arthroscopically assisted tendon graft fixation of the MMPRTs between January 2018 and September 2021. Functional recovery of the knee was evaluated and meniscal root healing status was assessed. The associations between different clinical factors and meniscal root healing status were analyzed. 98 (76.0%) patients had complete meniscal root healing with a minimum 2-year follow-up, and the Lysholm score, international knee documentation committee score, and visual analogue scale score were significantly improved at final follow-up (P < 0.001; respectively). Binary logistic regression models analysis and the receiver operating characteristic curve was performed to detect independent risk factors for incomplete healing, and these results indicated that age (OR = 1.095, P = 0.039), body mass index (BMI) (OR = 1.259, P = 0.018), preoperative meniscus extrusion (OR = 5.181, P < 0.001) and varus degree (OR = 7.764, P < 0.001) were the independent risk factors correlated with incomplete healing in patients with repaired MMPRTs. In conclusion, the arthroscopically assisted tendon graft fixation of the MMPRTs can provide good clinical and radiological outcome. Additionally, we identified age > 37.5 years, BMI > 24.5 kg/m2, preoperative meniscus extrusion > 2.7 mm and varus degree > 3.3° as independent risk factors correlated with incomplete meniscus root healing status.


Asunto(s)
Laceraciones , Meniscos Tibiales , Humanos , Adulto , Meniscos Tibiales/cirugía , Estudios Retrospectivos , Artroscopía/métodos , Rotura , Factores de Riesgo , Tendones/cirugía , Imagen por Resonancia Magnética
4.
Inorg Chem ; 62(46): 19153-19158, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-37934703

RESUMEN

The ability to conceptually mimic biomolecules to construct emergency-functional homospiral aggregates remains a long-standing challenge. Herein, we report artificial homohelical assembly by blending inorganic polyoxometalates (POMs) and organic cyclodextrin molecules. The chiral double-helical chains have been achieved by a left-hand arrangement of trimer-trimer. The trimer is formed by three {Mo8}@α-CD inclusive complexes as a Whittaker-style paddle wheel. During the process of assembly, chiral transfer and amplification from molecule to superstructure were observed. The enantioselective adsorption of the homohelical aggregate toward (R/S)-1,1'-binaphthyl-2,2'-diamine was further demonstrated. The interaction of {Mo8} and α-CD in solution was investigated. This work opens a wide scope for the design of a homohelix, enriching POM-based inorganic-organic materials.

5.
Dalton Trans ; 52(37): 13063-13067, 2023 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-37702078

RESUMEN

In this paper, we report the successful assembly of achiral {Ln6M} ([Ln6M(µ3-OH)8(acac)12(CH3O)x(CH3OH)y], Ln = La, M = Mn, Co, Fe) and chiral {Nd9Fe2} ([Nd9Fe2(µ4-O)(µ3-OH)14(acac)16(NO3)(CH3OH)2(H2O)3]) rare earth clusters using achiral rigid ligands and a transition metal doping strategy. {Ln6M} can be viewed as the fusion of two {Ln3M} tetrahedrons by sharing vertices. {Nd9Fe2} results from the fusion of four {Ln3M} tetrahedrons by vertice and edge sharing. The substitution of Ln with transition metal leads to changes in the coordination pattern around neighboring Ln, which triggers the switch of metal center chirality. This study demonstrates the potentiality of utilizing transition metal doping and rigid ligand to control the chirality of rare earth clusters. In addition, the photocatalytic CO2 activity of these transition metal-doped rare earth clusters has been studied.

6.
Food Chem ; 426: 136630, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37352710

RESUMEN

Pancreatic lipase inhibitors can reduce blood lipids by inactivating the catalytic activity of human pancreatic lipase, a key enzyme involved in triglyceride hydrolysis, which helps control some dyslipidemic diseases. The ability of Eucommia ulmoides tea to improve fat-related diseases is closely related to the natural inhibitory components of pancreatic lipase contained in the tea. In this study, fifteen pancreatic lipase inhibitors were screened and identified from Eucommia ulmoides tea by affinity-ultrafiltration combined UPLC-Q-Exactive Orbitrap/MS. Four representative components of geniposidic acid, quercetin-3-O-sambuboside, isochlorogenic acid A, and quercetin with high binding degrees were further verified by nanoscale differential scanning fluorimetry (nanoDSF) and enzyme inhibitory assays. The results of flow cytometry showed that they could significantly reduce the activity of pancreatic lipase in AR42J cells induced by palmitic acid in a concentration-dependent manner. Our findings suggest that Eucommia ulmoides tea may be a promising resource for pancreatic lipase inhibitors of natural origin.


Asunto(s)
Eucommiaceae , Humanos , Quercetina , Ultrafiltración , Lipasa ,
7.
Knee Surg Sports Traumatol Arthrosc ; 31(9): 3775-3783, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36790456

RESUMEN

PURPOSE: To evaluate the clinical and radiological outcomes of arthroscopically assisted tendon graft anatomic reinforced reconstruction of the medial meniscus posterior root tears (MMPRTs) and identify relevant factors affecting the correction of medial meniscal extrusion (MME). METHODS: Fifty-three MMPRTs patients who underwent arthroscopically assisted tendon graft reconstruction of the meniscal root between 2018 and 2020 were evaluated retrospectively. the patients were divided into 2 groups according to the correction of MME (maintained MME group: 32 cases vs. increased MME group: 21 cases). The clinical and radiological outcomes of arthroscopically assisted tendon graft reconstruction of the meniscal root, including postoperative correction of MME and functional recovery of the knee were assessed in this study, and potential independent risk factors that could influence the correction of MME were also evaluated. RESULTS: The functional recovery of the knee was significantly improved at the end of follow-up (P < 0.001; respectively), furthermore, a comparison of the final functional outcomes between the groups showed that the mean Lysholm score and IKDC score of the maintained MME group were significantly improved than those of increased MME group. 60.4% had good correction of MME, and patients with complete healing had better extrusion correction than those with partial healing and non-healing. Binary logistic regression models analysis indicated that the age (OR = 1.053, P = 0.048), BMI (OR = 1.376, P = 0.004), meniscus root healing status (OR = 7.701, P = 0.005), HKA degree (OR = 1.891, P = 0.011) and preoperative symptom duration (OR = 1.055, P = 0.013) were the independent risk factors correlated with correction of MME. Additionally, the ROC curve demonstrated the cut-off values of the Age, BMI, HKA degree and preoperative symptom duration were 46.0 years, 22.5 kg/m2, 3.2° and 9.5 months, respectively, CONCLUSIONS: The arthroscopically assisted tendon graft anatomic reinforced reconstruction of the meniscal root showed clinical improvement and prevented the progression of postoperative MME. Additionally, younger patients, lower BMI, complete meniscus root healing, lower HKA degree and shorter preoperative symptom duration were the independent risk factors correlated with the good correction of MME in patients with repaired MMPRTs. LEVEL OF EVIDENCE: Level IV.


Asunto(s)
Imagen por Resonancia Magnética , Meniscos Tibiales , Humanos , Persona de Mediana Edad , Meniscos Tibiales/cirugía , Estudios Retrospectivos , Índice de Masa Corporal , Artroscopía , Factores de Riesgo
8.
BMC Musculoskelet Disord ; 23(1): 1094, 2022 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-36517773

RESUMEN

BACKGROUND: Many surgeries have not reversed or prevented progressive symptomatic knee arthritis, and there is no consensus regarding the ideal repair or reconstruction technique for meniscal root treatment. Additionally, there is a lack of studies comparing the clinical efficacy evaluation of different repair techniques. The aim of the present study is to compare the clinical efficacy and healing rates of meniscus root in the treatment of medial meniscus posterior root tear (MMPRT) with the arthroscopically assisted meniscus root reconstruction with gracilis autograft and transtibial pull-out technique. METHODS: Patients with MMPRT (type II) who received treatment of posterior meniscus root attachment point through the tibial tunnel between January 2018 and April 2019 were included in this study. Patients were divided into 2 groups (arthroscopically assisted gracilis autograft reconstruction technique: 29 cases; transtibial pull-out technique group: 35 cases) according to the different treatment methods. The mean follow-up period was 26.9 ± 2.3 months. The demographics, functional recovery of the knee, and meniscus root healing rates (assessed using knee magnetic resonance imaging (MRI) at the final follow-up) were compared between the two groups. RESULTS: There was a statistically significant improvement in the Lysholm score, international knee documentation committee (IKDC) score, and visual analogue scale (VAS) score (P < 0.001 in both groups). Additionally, compared with the transtibial pull-out repair group, the arthroscopically assisted reconstruction with gracilis autograft showed significant improvement in the meniscus root healing rates, Lysholm score, and IKDC score at the end of follow-up (P < 0.05). CONCLUSIONS: Compared with the transtibial pull-out technique, the arthroscopically assisted meniscus root reconstruction with gracilis autograft was advantageous for treating these patients with superior clinical outcome and higher meniscus root healing rates. LEVEL OF EVIDENCE: Level III.


Asunto(s)
Meniscos Tibiales , Lesiones de Menisco Tibial , Humanos , Meniscos Tibiales/diagnóstico por imagen , Meniscos Tibiales/cirugía , Lesiones de Menisco Tibial/diagnóstico por imagen , Lesiones de Menisco Tibial/cirugía , Autoinjertos , Artroscopía/métodos , Estudios Retrospectivos , Rotura , Medición de Resultados Informados por el Paciente , Imagen por Resonancia Magnética
9.
Artículo en Inglés | MEDLINE | ID: mdl-36096637

RESUMEN

The nucleus, a genome-containing organelle eponymous of eukaryotes, is enclosed by a double membrane continuous with the endoplasmic reticulum. The nuclear pore complex (NPC) is an ∼110-MDa, ∼1000-protein channel that selectively transports macromolecules across the nuclear envelope and thus plays a central role in the regulated flow of genetic information from transcription to translation. Its size, complexity, and flexibility have hindered determination of atomistic structures of intact NPCs. Recent studies have overcome these hurdles by combining biochemical reconstitution and docking of high-resolution structures of NPC subcomplexes into cryo-electron tomographic reconstructions with biochemical and physiological validation. Here, we provide an overview of the near-atomic composite structure of the human NPC, a milestone toward unlocking a molecular understanding of mRNA export, NPC-associated diseases, and viral host-pathogen interactions, serving as a paradigm for studying similarly large complexes.


Asunto(s)
Núcleo Celular , Poro Nuclear , Humanos , Poro Nuclear/química , Poro Nuclear/metabolismo , Transporte Activo de Núcleo Celular , Retículo Endoplásmico , Eucariontes , Membrana Nuclear/metabolismo
10.
BMC Musculoskelet Disord ; 23(1): 756, 2022 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-35933337

RESUMEN

BACKGROUND: The aim of the present study was to compare the clinical efficacy of arthroscopic-assisted fixation using the Tight-rope system and clavicular hook plate fixation in the treatment of Neer IIB distal clavicle fractures. METHODS: We enrolled 48 consecutive patients with Neer IIB distal clavicle fractures who were treated at our institution from February 2016 and August 2020. These patients were divided into 2 groups based on the fixation method (16 cases with Tight-rope system and 32 cases with clavicular hook plate), and demographics and clinical characteristics of patients in different groups were compared. RESULTS: All 48 patients had functional outcome scores of the affected shoulder available at a mean of 23.8 ± 5.1 months, and there was a statistically significant improvement in the constant score, American shoulder and elbow surgeons (ASES) score, visual analogue scale (VAS) score at the end of follow-up (p < 0.001 respectively). However, the smaller length of skin incision, less estimated blood loss and shorter hospital stay were detected in the Tight-rope technique group patients than those of clavicular hook plate group patients (p < 0.001, respectively). Furthermore, the constant score, ASES score and VAS score were significantly improved in the Tight-rope technique group patients than those of clavicular hook plate group patients (p < 0.05, respectively). CONCLUSIONS: Both Tight-rope technique and clavicular hook plate fixation can provide satisfactory clinical and radiological results in the treatment of distal clavicular Neer IIB fracture. However, arthroscopic-assisted fixation using the Tight-rope technique showed better results in terms of length of hospital stay, surgical trauma, clinical scores, and diagnose and treat concomitant glenohumeral pathologies. LEVELS OF EVIDENCE: III, Case-control study Retrospective comparative study.


Asunto(s)
Clavícula , Fracturas Óseas , Placas Óseas , Estudios de Casos y Controles , Clavícula/diagnóstico por imagen , Clavícula/lesiones , Clavícula/cirugía , Fijación Interna de Fracturas/efectos adversos , Fijación Interna de Fracturas/métodos , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/cirugía , Humanos , Estudios Retrospectivos , Resultado del Tratamiento
11.
Science ; 376(6598): eabm9129, 2022 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-35679405

RESUMEN

INTRODUCTION The subcellular compartmentalization of eukaryotic cells requires selective transport of folded proteins and protein-nucleic acid complexes. Embedded in nuclear envelope pores, which are generated by the circumscribed fusion of the inner and outer nuclear membranes, nuclear pore complexes (NPCs) are the sole bidirectional gateways for nucleocytoplasmic transport. The ~110-MDa human NPC is an ~1000-protein assembly that comprises multiple copies of ~34 different proteins, collectively termed nucleoporins. The symmetric core of the NPC is composed of an inner ring encircling the central transport channel and outer rings formed by Y­shaped coat nucleoporin complexes (CNCs) anchored atop both sides of the nuclear envelope. The outer rings are decorated with compartment­specific asymmetric nuclear basket and cytoplasmic filament nucleoporins, which establish transport directionality and provide docking sites for transport factors and the small guanosine triphosphatase Ran. The cytoplasmic filament nucleoporins also play an essential role in the irreversible remodeling of messenger ribonucleoprotein particles (mRNPs) as they exit the central transport channel. Unsurprisingly, the NPC's cytoplasmic face represents a hotspot for disease­associated mutations and is commonly targeted by viral virulence factors. RATIONALE Previous studies established a near-atomic composite structure of the human NPC's symmetric core by combining (i) biochemical reconstitution to elucidate the interaction network between symmetric nucleoporins, (ii) crystal and single-particle cryo-electron microscopy structure determination of nucleoporins and nucleoporin complexes to reveal their three-dimensional shape and the molecular details of their interactions, (iii) quantitative docking in cryo-electron tomography (cryo-ET) maps of the intact human NPC to uncover nucleoporin stoichiometry and positioning, and (iv) cell­based assays to validate the physiological relevance of the biochemical and structural findings. In this work, we extended our approach to the cytoplasmic filament nucleoporins to reveal the near-atomic architecture of the cytoplasmic face of the human NPC. RESULTS Using biochemical reconstitution, we elucidated the protein-protein and protein-RNA interaction networks of the human and Chaetomium thermophilum cytoplasmic filament nucleoporins, establishing an evolutionarily conserved heterohexameric cytoplasmic filament nucleoporin complex (CFNC) held together by a central heterotrimeric coiled­coil hub that tethers two separate mRNP­remodeling complexes. Further biochemical analysis and determination of a series of crystal structures revealed that the metazoan­specific cytoplasmic filament nucleoporin NUP358 is composed of 16 distinct domains, including an N­terminal S­shaped α­helical solenoid followed by a coiled­coil oligomerization element, numerous Ran­interacting domains, an E3 ligase domain, and a C­terminal prolyl­isomerase domain. Physiologically validated quantitative docking into cryo-ET maps of the intact human NPC revealed that pentameric NUP358 bundles, conjoined by the oligomerization element, are anchored through their N­terminal domains to the central stalk regions of the CNC, projecting flexibly attached domains as far as ~600 Å into the cytoplasm. Using cell­based assays, we demonstrated that NUP358 is dispensable for the architectural integrity of the assembled interphase NPC and RNA export but is required for efficient translation. After NUP358 assignment, the remaining 4-shaped cryo­ET density matched the dimensions of the CFNC coiled­coil hub, in close proximity to an outer-ring NUP93. Whereas the N-terminal NUP93 assembly sensor motif anchors the properly assembled related coiled­coil channel nucleoporin heterotrimer to the inner ring, biochemical reconstitution confirmed that the NUP93 assembly sensor is reused in anchoring the CFNC to the cytoplasmic face of the human NPC. By contrast, two C. thermophilum CFNCs are anchored by a divergent mechanism that involves assembly sensors located in unstructured portions of two CNC nucleoporins. Whereas unassigned cryo­ET density occupies the NUP358 and CFNC binding sites on the nuclear face, docking of the nuclear basket component ELYS established that the equivalent position on the cytoplasmic face is unoccupied, suggesting that mechanisms other than steric competition promote asymmetric distribution of nucleoporins. CONCLUSION We have substantially advanced the biochemical and structural characterization of the asymmetric nucleoporins' architecture and attachment at the cytoplasmic and nuclear faces of the NPC. Our near­atomic composite structure of the human NPC's cytoplasmic face provides a biochemical and structural framework for elucidating the molecular basis of mRNP remodeling, viral virulence factor interference with NPC function, and the underlying mechanisms of nucleoporin diseases at the cytoplasmic face of the NPC. [Figure: see text].


Asunto(s)
Citoplasma , Proteínas Fúngicas , Proteínas de Complejo Poro Nuclear , Poro Nuclear , Transporte de ARN , ARN Mensajero , Chaetomium , Microscopía por Crioelectrón , Citoplasma/química , Proteínas Fúngicas/química , Humanos , Chaperonas Moleculares/química , Poro Nuclear/química , Proteínas de Complejo Poro Nuclear/química , Conformación Proteica , ARN Mensajero/metabolismo
12.
Science ; 376(6598): eabm9798, 2022 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-35679425

RESUMEN

INTRODUCTION In eukaryotic cells, the selective bidirectional transport of macromolecules between the nucleus and cytoplasm occurs through the nuclear pore complex (NPC). Embedded in nuclear envelope pores, the ~110-MDa human NPC is an ~1200-Å-wide and ~750-Å-tall assembly of ~1000 proteins, collectively termed nucleoporins. Because of the NPC's eightfold rotational symmetry along the nucleocytoplasmic axis, each of the ~34 different nucleoporins occurs in multiples of eight. Architecturally, the NPC's symmetric core is composed of an inner ring encircling the central transport channel and two outer rings anchored on both sides of the nuclear envelope. Because of its central role in the flow of genetic information from DNA to RNA to protein, the NPC is commonly targeted in viral infections and its nucleoporin constituents are associated with a plethora of diseases. RATIONALE Although the arrangement of most scaffold nucleoporins in the NPC's symmetric core was determined by quantitative docking of crystal structures into cryo-electron tomographic (cryo-ET) maps of intact NPCs, the topology and molecular details of their cohesion by multivalent linker nucleoporins have remained elusive. Recently, in situ cryo-ET reconstructions of NPCs from various species have indicated that the NPC's inner ring is capable of reversible constriction and dilation in response to variations in nuclear envelope membrane tension, thereby modulating the diameter of the central transport channel by ~200 Å. We combined biochemical reconstitution, high-resolution crystal and single-particle cryo-electron microscopy (cryo-EM) structure determination, docking into cryo-ET maps, and physiological validation to elucidate the molecular architecture of the linker-scaffold interaction network that not only is essential for the NPC's integrity but also confers the plasticity and robustness necessary to allow and withstand such large-scale conformational changes. RESULTS By biochemically mapping scaffold-binding regions of all fungal and human linker nucleoporins and determining crystal and single-particle cryo-EM structures of linker-scaffold complexes, we completed the characterization of the biochemically tractable linker-scaffold network and established its evolutionary conservation, despite considerable sequence divergence. We determined a series of crystal and single-particle cryo-EM structures of the intact Nup188 and Nup192 scaffold hubs bound to their Nic96, Nup145N, and Nup53 linker nucleoporin binding regions, revealing that both proteins form distinct question mark-shaped keystones of two evolutionarily conserved hetero­octameric inner ring complexes. Linkers bind to scaffold surface pockets through short defined motifs, with flanking regions commonly forming additional disperse interactions that reinforce the binding. Using a structure­guided functional analysis in Saccharomyces cerevisiae, we confirmed the robustness of linker­scaffold interactions and established the physiological relevance of our biochemical and structural findings. The near-atomic composite structures resulting from quantitative docking of experimental structures into human and S. cerevisiae cryo-ET maps of constricted and dilated NPCs structurally disambiguated the positioning of the Nup188 and Nup192 hubs in the intact fungal and human NPC and revealed the topology of the linker-scaffold network. The linker-scaffold gives rise to eight relatively rigid inner ring spokes that are flexibly interconnected to allow for the formation of lateral channels. Unexpectedly, we uncovered that linker­scaffold interactions play an opposing role in the outer rings by forming tight cross-link staples between the eight nuclear and cytoplasmic outer ring spokes, thereby limiting the dilatory movements to the inner ring. CONCLUSION We have substantially advanced the structural and biochemical characterization of the symmetric core of the S. cerevisiae and human NPCs and determined near-atomic composite structures. The composite structures uncover the molecular mechanism by which the evolutionarily conserved linker­scaffold establishes the NPC's integrity while simultaneously allowing for the observed plasticity of the central transport channel. The composite structures are roadmaps for the mechanistic dissection of NPC assembly and disassembly, the etiology of NPC­associated diseases, the role of NPC dilation in nucleocytoplasmic transport of soluble and integral membrane protein cargos, and the anchoring of asymmetric nucleoporins. [Figure: see text].


Asunto(s)
Proteínas de Complejo Poro Nuclear , Poro Nuclear , Proteínas de Saccharomyces cerevisiae , Microscopía por Crioelectrón , Humanos , Modelos Moleculares , Poro Nuclear/química , Proteínas de Complejo Poro Nuclear/química , Conformación Proteica , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/química
13.
Front Oncol ; 12: 859625, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35494065

RESUMEN

Objective: Prostate cancer and hyperplasia require different treatment strategies and have completely different outcomes; thus, preoperative identification of prostate cancer and hyperplasia is very important. The purpose of this study was to evaluate the application value of magnetic resonance imaging (MRI)-derived radiomic nomogram based on T2-weighted images (T2WI) in differentiating prostate cancer and hyperplasia. Materials and Methods: One hundred forty-six patients (66 cases of prostate cancer and 80 cases of prostate hyperplasia) who were confirmed by surgical pathology between September 2019 and September 2019 were selected. We manually delineated T2WI of all patients using ITK-SNAP software and radiomic analysis using Analysis Kit (AK) software. A total of 396 tumor texture features were extracted. Subsequently, the effective features were selected using the LASSO algorithm, and the radiomic feature model was constructed. Next, combined with independent clinical risk factors, a multivariate Logistic regression model was used to establish a radiomic nomogram. The receiver operator characteristic (ROC) curve was used to evaluate the prediction performance of the radiomic nomogram. Finally, the clinical application value of the nomogram was evaluated by decision curve analysis. Results: The PSA and the selected imaging features were significantly correlated with the differential diagnosis of prostate cancer and hyperplasia. The radiomic model had good discrimination efficiency for prostate cancer and hyperplasia. The training set (AUC = 0.85; 95% CI: 0.77-0.92) and testing set (AUC = 0.84; 95% CI: 0.72-0.96) were effective. The radiomic nomogram, combined with the radiomic characteristics of MRI and independent clinical risk factors, showed better differentiation efficiency in the training set (AUC = 0.91; 95% CI: 0.85-0.97) and testing set (AUC = 0.90; 95% CI: 0.81-0.99). The decision curve showed the clinical application value of the radiomic nomogram. Conclusion: The radiomic nomogram of T2-MRI combined with clinical risk factors can easily identify prostate cancer and hyperplasia. It also provides suggestions for further clinical events.

14.
BMC Musculoskelet Disord ; 22(1): 720, 2021 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-34425799

RESUMEN

BACKGROUND: To assess the utility of routine postoperative laboratory tests for patients undergoing high tibial osteotomy (HTO) surgery. METHODS: The associations between clinical risk factors and postoperative clinical treatment were analyzed. Additionally, a logistic regression analysis was performed to detect independent risk factors for patients requiring postoperative clinical treatment. RESULTS: A total of 482 patients with symptomatic isolated medial compartment osteoarthritis from January 2015 to May 2020 were included in the present study and underwent examination by the full set of postoperative laboratory tests within 3 days after HTO surgery. However, only a small proportion of the patients with anemia (3.9 %), hypoalbuminemia (4.1 %), and abnormal serum potassium levels (3.5 %) required clinical intervention after surgery. Binary logistic regression analysis showed that the body mass index (BMI), preoperative hemoglobin level, estimated blood loss and operative duration were independent risk factors for postoperative blood transfusion in patients who underwent HTO surgery, and factors associated with albumin supplementation were female sex and preoperative albumin level. In addition, these results indicated that preoperative potassium was potential risk factor for patients who required potassium supplementation postoperatively. CONCLUSIONS: Based on the analysis, we conclude that routinely ordering postoperative laboratory tests after HTO surgery is unnecessary. However, for patients with identified risk factors, routine postoperative laboratory tests are still needed.


Asunto(s)
Osteotomía , Transfusión Sanguínea , Femenino , Humanos , Periodo Posoperatorio , Estudios Retrospectivos
15.
J Orthop Surg (Hong Kong) ; 29(2): 23094990211010562, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33896269

RESUMEN

INTRODUCTION: The purpose of this study was to compare the results of arthroscopically assisted reduction of acute acromioclavicular (AC) joint separations with the Tight-Rope technique with results of clavicular hook plate fixation. MATERIALS AND METHODS: The 28 patients with acute high-grade AC joint dislocation were treated with arthroscopic assisted fixation using the Tight-Rope system, the arthroscopic evaluation and treatment of glenohumeral lesions were performed before AC ligament reconstruction. Each Tight-Rope technique group patient was matched with three controls that underwent clavicular hook plate fixation, and preoperation and postoperative visual analogue scale (VAS) and functional recovery (Constant Score) of the shoulder joint was assessed,. Furthermore, the demographics and clinical characteristics were compared between the two groups. RESULTS: All patients had clinical and radiological results available at 2 years or greater (mean: 34; range: 24-72 months), they were statistically significant improvement in the constant score and VAS score at the end of follow-up respectively (P < 0.001). Compared with the clavicular hook plate group, Tight-Rope system group patients were incurred significant statistically lower skin incision, hospitalization time and estimated blood loss (P < 0.001), and the constant score and VAS score at the end of follow-up was significantly higher in the Tight-Rope group (P < 0.001). Patients who underwent clavicular hook plate had a higher incidence of fixation failure [10 cases (11.9%) versus 2 cases (7.1%)] than those of the Tight-Rope system group. CONCLUSIONS: The Tight-Rope technique is advantageous for treating these patients because it is a minimally invasive procedure with low complications and superior clinical outcomes.


Asunto(s)
Articulación Acromioclavicular/cirugía , Luxaciones Articulares/cirugía , Procedimientos Ortopédicos/métodos , Articulación Acromioclavicular/diagnóstico por imagen , Articulación Acromioclavicular/lesiones , Enfermedad Aguda , Adulto , Artroscopía , Placas Óseas , Femenino , Humanos , Luxaciones Articulares/diagnóstico por imagen , Ligamentos Articulares/cirugía , Masculino , Procedimientos Ortopédicos/instrumentación , Recuperación de la Función , Resultado del Tratamiento
16.
Artículo en Inglés | MEDLINE | ID: mdl-33210545

RESUMEN

The primary aim was to identify potential risk factors for early conversion to total knee arthroplasty (TKA) in patients with high tibial osteotomy (HTO) surgery. A retrospective study was conducted and 240 patients received HTO surgery between January 2008 and January 2014 were included in this study. The associations between different clinical factors and HTO survivorship were analyzed. A logistic regression analysis was performed to detect independent risk factors for HTO survivorship. The cut-off value, sensitivity and specificity of these independent factors were calculated by receiver operating characteristic (ROC) curve. In this study, thirty-five (14.6%) patients were early conversion to TKA within a 5-year follow-up. These results indicated that age, body mass index (BMI), preoperative Kellgren-Lawrence (K-L) grade and preoperative visual analogue scale (VAS) score were potential risk factors for HTO survivorship. The cut-off values of those factors were 60 years, 25.35 kg/m2, 2 and 5, respectively. The combination of age, BMI, preoperative K-L grade and preoperative VAS score has the highest predictive value for HTO survivorship (AUC = 0.896, P < 0.001). Based on the present study, the five-year HTO survivorship for the treatment of medial compartment osteoarthritis of the knee was approximately 85.4%. We identified age >60 years, BMI >25.35 kg/m2, preoperative K-L grade >2 and preoperative VAS score >5 as independent risk factors for early conversion to TKA in patients with HTO surgery, and those factors combined had the highest predictive value for predicting early conversion to TKA.

17.
Technol Health Care ; 25(6): 1029-1039, 2017 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-28759981

RESUMEN

Knowledge of the pressure distribution around human thorax in blast help to understand the injury mechanisms and their assessment. To investigate the transmission mechanism of the pressure on human thorax in blast, a three dimension surface model of human thorax was constructed in this work. To increase the precious of this model, tetrahedron element division method was applied to transfer the rough 3D surface model to hexahedral elements model. Using this model, the high pressure duration was computationally solved using numerical simulation of the hexahedral elements. Simulation results showed that the apex of lungs was subjected to the largest stress in a blast. In order to verify this result, an animal experiment was performed on a dog. The animal experimental results was shown to have a same variation tendency with the calculation results based on our numerical model of human thorax, which made this model reliable for the blast injury research.


Asunto(s)
Traumatismos por Explosión/fisiopatología , Simulación por Computador , Modelos Biológicos , Tórax/fisiopatología , Animales , Fenómenos Biomecánicos , Perros , Análisis de Elementos Finitos , Humanos , Pulmón/fisiopatología , Presión
18.
Neuropsychiatr Dis Treat ; 13: 1471-1482, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28652747

RESUMEN

PURPOSE: Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder that can damage cognitive function. However, the functional network organization remains poorly understood. The aim of this study was to investigate the topological properties of OSA patients using a graph theoretical analysis. PATIENTS AND METHODS: A total of 30 male patients with untreated severe OSA and 25 male education- and age-matched good sleepers (GSs) underwent functional magnetic resonance imaging (MRI) examinations. Clinical and cognitive evaluations were conducted by an experienced psychologist. GRETNA (a toolbox for topological analysis of imaging connectomics) was used to construct the brain functional network and calculate the small-world properties (γ, λ, σ, Eglob, and Eloc). Relationships between these small-world properties and clinical and neuropsychological assessments were investigated in OSA patients. RESULTS: The networks of both OSA patients and GSs exhibited efficient small-world topology over the sparsity range of 0.05-0.40. Compared with GSs, the OSA group had significantly decreased γ, but significantly increased λ and σ. The OSA group's brain network showed significantly decreased Eglob (P<0.05) over the sparsity range of 0.09-0.15, but significantly increased Eloc over the sparsity range of 0.23-0.40. In OSA patients, γ was significantly negatively correlated with apnea-hypopnea index (AHI; r=-0.326, P=0.015) and Epworth Sleepiness Scale (ESS; r=-0.274, P=0.043), λ was significantly positively correlated with AHI (r=0.373, P=0.005) and ESS (r=0.269, P=0.047), and σ was significantly negatively correlated with AHI (r=-0.363, P=0.007) and ESS (r=-0.295, P=0.029). CONCLUSION: Our results suggest that the high degree of local integration and integrity of the brain connections in OSA patients may be disrupted. The topological alterations of small-world properties may be the mechanism of cognitive impairment in OSA patients. In addition, σ, γ, and λ could be used as a quantitative physiological index for auxiliary clinical diagnoses.

19.
Sleep Breath ; 21(2): 487-495, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28210922

RESUMEN

STUDY OBJECTIVES: The aim of this study is to investigate changes in regional cerebral blood flow (rCBF) in awake people with untreated severe obstructive sleep apnoea (OSAs) compared with good sleepers (GSs). DESIGN: Arterial spin labelling perfusion imaging was used to quantify cerebral perfusion based on resting-state functional magnetic resonance imaging (MRI). SETTING: Lying supine in a 3.0-T magnetic resonance imaging scanner in the night was done. PARTICIPANTS: Included in this study were 30 subjects with OSA (males; mean age 38.4 years, range 25-55) and 30 controls (males; mean age: 38.3 years, range 26-52) matched for age and years of education. RESULTS: Compared with GSs, participants with severe OSA had reduced rCBF in the left cerebellum posterior lobe, left temporal lobe, right medial frontal gyrus, and bilateral parahippocampal gyrus and increased rCBF in the bilateral superior frontal gyrus. The lower mean CBF in the right parahippocampal gyrus exhibited a significant positive correlation with arousal index (r = 0.365, P = 0.047). The increased mean CBF in the left superior frontal gyrus exhibited a significant positive correlation with the longest apnoea time (r = 0.422, P = 0.020), and the increased mean CBF in the right superior frontal gyrus exhibited a significant positive correlation with the longest apnoea time (r = 0.447, P = 0.013). CONCLUSIONS: Our results show that the altered rCBF pattern in the left cerebellum posterior lobe, left temporal lobe, left medial frontal gyrus, bilateral parahippocampal gyrus and superior frontal gyrus in patients have with severe OSA. The arterial spin labelling perfusion imaging method is a useful non-invasive imaging tool for detection of early changes in the regional cerebral blood flow in patients with OSA.


Asunto(s)
Encéfalo/irrigación sanguínea , Espectroscopía de Resonancia por Spin del Electrón , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/fisiopatología , Marcadores de Spin , Adulto , Dominancia Cerebral/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Flujo Sanguíneo Regional/fisiología
20.
PLoS One ; 11(10): e0164031, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27723821

RESUMEN

PURPOSE: Obstructive sleep apnea (OSA) has been associated with changes in brain structure and regional function in certain brain areas. However, the functional features of network organization in the whole brain remain largely uncertain. The purpose of this study was to identify the OSA-related spatial centrality distribution of the whole brain functional network and to investigate the potential altered intrinsic functional hubs. METHODS: Forty male patients with newly confirmed severe OSA on polysomnography, and well-matched good sleepers, participated in this study. All participants underwent a resting-state functional MRI scan and clinical and cognitive evaluation. Voxel-wise degree centrality (DC) was measured across the whole brain, and group difference in DC was compared. The relationship between the abnormal DC value and clinical variables was assessed using a linear correlation analysis. RESULTS: Remarkably similar spatial distributions of the functional hubs (high DC) were found in both groups. However, OSA patients exhibited a pattern of significantly reduced regional DC in the left middle occipital gyrus, posterior cingulate cortex, left superior frontal gyrus, and bilateral inferior parietal lobule, and DC was increased in the right orbital frontal cortex, bilateral cerebellum posterior lobes, and bilateral lentiform nucleus, including the putamen, extending to the hippocampus, and the inferior temporal gyrus, which overlapped with the functional hubs. Furthermore, a linear correlation analysis revealed that the DC value in the posterior cingulate cortex and left superior frontal gyrus were positively correlated with Montreal cognitive assessment scores, The DC value in the left middle occipital gyrus and bilateral inferior parietal lobule were negatively correlated with apnea-hypopnea index and arousal index in OSA patients. CONCLUSION: Our findings suggest that OSA patients exhibited specific abnormal intrinsic functional hubs including relatively reduced and increased DC. This expands our understanding of the functional characteristics of OSA, which may provide new insights into understanding the dysfunction and pathophysiology of OSA patients.


Asunto(s)
Encéfalo , Imagen por Resonancia Magnética , Red Nerviosa , Polisomnografía , Apnea Obstructiva del Sueño , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Apnea Obstructiva del Sueño/diagnóstico por imagen , Apnea Obstructiva del Sueño/fisiopatología
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