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The precision of previous cancer research based on tumor spheroids, especially the microgel-encapsulating tumor spheroids, was limited by the high heterogeneity in the tumor spheroid size and shape. Here, we reported a user-friendly solenoid valve-based sorter to reduce this heterogeneity. The artificial intelligence algorithm was employed to detect and segmentate the tumor spheroids in real-time for the size and shape calculation. A simple off-chip solenoid valve-based sorting actuation module was proposed to sort out target tumor spheroids with the desired size and shape. Utilizing the developed sorter, we successfully uncovered the drug response variations on cisplatin of lung tumor spheroids in the same population but with different sizes and shapes. Moreover, with this sorter, the precision of drug testing on the spheroid population level was improved to a level comparable to the precise but complex single spheroid analysis. The developed sorter also exhibits significant potential for organoid morphology and sorting for precision medicine research.
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Alzheimer's disease (AD) is an intricate disorder involving amyloid deposits, neurofibrillary tangles, and chronic neuroinflammation. Though current Aß-directed immunotherapies effectively eliminate amyloid plaques, their limited clinical benefits and notable safety concerns arise from overlooking two other neglected neurodegenerative features. Compelling evidence highlights synergistic cooperation between Aß and tau, underscoring the imperative need to develop combinational therapies to target the diverse pathologies of AD. In this study, we present a dual AD vaccine combining Aß and pTau vaccines, eliciting robust and enduring antibody responses against pathological Aß and pTau in 3xTg transgenic mice. It significantly eradicated Aß plaques and pTau tangles, suppressed neuroinflammatory factors, and markedly enhancing cognitive abilities in 3xTg mice. Mechanistically, peripheral antibodies penetrated the brain, recognizing and inhibiting Aß and pTau aggregation, thereby reducing their cytotoxicity. In summary, this innovative multi-targeting immunotherapy remarkably ameliorates diverse AD pathologies, demonstrating maximum benefits in slowing the clinical progression of AD.
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The pursuit of highly efficient electrocatalysts for the alkaline hydrogen evolution reaction (HER) is of paramount importance for water splitting. However, it is still a formidable task in Mo2C-based materials because of the agglomeration and strong Mo-H binding of Mo2C units. Herein, a novel CeOCl-CeO2/Mo2C heterostructure nesting within a three-dimensional porous nitrogen-doped carbon matrix has been designed and used for catalyzing HER via simultaneous morphology and heterointerface engineering. As expected, the optimal CeOCl-CeO2(0.2)/Mo2C@3DNC exhibits impressive HER activity, with a low overpotential of 156 mV at a current density of 10 mA cm-2 coupled with a slight Tafel slope of 62.20 mV dec-1. Introducing a Ce promoter, that is CeOCl and CeO2, would endow the interface with an internal electric field and electron redistribution between CeOCl-CeO2 and Mo2C induced by the heterogeneous work function difference. Moreover, experimental investigation and density functional calculations confirm that the CeOCl-CeO2/Mo2C heterointerface can downshift the d-band center of the active Mo center, weakening the strength of the Mo-H coupling. This proposed concept, engineering Ce-based promoters into active entities involved in the heterostructure to modulate intermediate adsorption, offers a great opportunity for the design of superior electrocatalysts for energy conversion.
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Hot-carrier transistors are a class of devices that leverage the excess kinetic energy of carriers. Unlike regular transistors, which rely on steady-state carrier transport, hot-carrier transistors modulate carriers to high-energy states, resulting in enhanced device speed and functionality. These characteristics are essential for applications that demand rapid switching and high-frequency operations, such as advanced telecommunications and cutting-edge computing technologies1-5. However, the traditional mechanisms of hot-carrier generation are either carrier injection6-11 or acceleration12,13, which limit device performance in terms of power consumption and negative differential resistance14-17. Mixed-dimensional devices, which combine bulk and low-dimensional materials, can offer different mechanisms for hot-carrier generation by leveraging the diverse potential barriers formed by energy-band combinations18-21. Here we report a hot-emitter transistor based on double mixed-dimensional graphene/germanium Schottky junctions that uses stimulated emission of heated carriers to achieve a subthreshold swing lower than 1 millivolt per decade beyond the Boltzmann limit and a negative differential resistance with a peak-to-valley current ratio greater than 100 at room temperature. Multi-valued logic with a high inverter gain and reconfigurable logic states are further demonstrated. This work reports a multifunctional hot-emitter transistor with significant potential for low-power and negative-differential-resistance applications, marking a promising advancement for the post-Moore era.
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We theoretically study the second-harmonic generation (SHG) of two-dimensional (2D) materials excited by a Laguerre-Gaussian (LG) beam at normal incidence and provide a method to distinguish SHG induced by the electric dipole (ED) interaction and SHG induced by the electric quadrupole and magnetic dipole (EQ-MD) interaction by their different dependence on the LG beam parameters, including the effective spot area v02 and the order of orbital angular momentum (OAM) m. In an approximation of neglecting reflection and taking a beam radius to infinity, the intensity of the ED induced SHG is proportional to F m/v02 with Fm = 2-2|m|(2|m|)!/(π(|m|!)2), while the EQ-MD induced one is proportional to (4|m|+2)F m/v04. An in-plane isotropic substrate can strongly affect the signal amplitude but slightly change the v0 and m dependence. Our results provide an all-optical way to detect the OAM by SHG, as well as a theoretical basis for studying the EQ-MD induced SHG by the LG beams.
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Noncoding RNAs (ncRNAs) have emerged as pivotal regulators of gene expression, and have attracted significant attention because of their various roles in biological processes. These molecules have transcriptional activity despite their inability to encode proteins. Moreover, research has revealed that ncRNAs, especially microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), are linked to pervasive regulators of kidney disease, including anti-inflammatory, antiapoptotic, antifibrotic, and proangiogenic actions in acute and chronic kidney disease. Although the exact therapeutic mechanism of ncRNAs remains uncertain, their value in treatment has been studied in clinical trials. The numerous renal diseases and the beneficial or harmful effects of NcRNAs on the kidney will be discussed in this article. Afterward, exploring the biological characteristics of ncRNAs, as well as their purpose and potential contributions to acute and chronic renal disease, were explored. This may offer guidance for treating both acute and long-term kidney illnesses, as well as insights into the potential use of these indicators as kidney disease biomarkers.
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BACKGROUND: Robotic neck dissection is emerging as an alternative to conventional open neck dissection. However, the oncologic safety of robotic elective neck dissection (END) and its indications in early-stage tongue cancer are unclear. METHODS: We retrospectively reviewed the data of 78 patients who underwent transoral excision for T1, T2 squamous cell carcinoma of tongue with simultaneous ipsilateral END. Patients were assigned to two groups: the robotic group (n = 32)-postauricular face-lift -and the conventional group (n = 46)- transcervical incision. We compared the survival, clinical, pathologic and cosmetic outcomes of the two groups, and evaluated the number of retrieved lymph nodes and robot console time in the robotic group. RESULTS: The mean age was lower in the robotic group (43.6 ± 12.8 vs. 55.8 ± 14.0, p < 0.001) and the conventional group had more T2 patients (p = 0.01). The mean operation time was significantly longer in the robotic group than the conventional group (178.81 ± 33.9 vs. 92.28 ± 16.7, p < 0.001). The mean number of retrieved lymph nodes was not significantly different between the two groups (19.22 ± 8.51 vs. 20.7 ± 11.4, p = 0.41). The 5-year disease-free survival rate was not significantly different between the two groups (93.6 % vs. 82.9 %, p = 0.59). Overall scar satisfaction assessed by VAS score, the robotic group showed significantly better results compared to the conventional group (8.38 vs. 5.86, p = 0.033). CONCLUSION: Robotic END by a postauricular facelift approach is a feasible and safe approach for early-stage tongue cancer.
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This study introduces a novel 3D scaffold for bone regeneration, composed of silk fibroin, chitosan, nano-hydroxyapatite, LL-37 antimicrobial peptide, and pamidronate. The scaffold addresses a critical need in bone tissue engineering by simultaneously combating bone infections and promoting bone growth. LL-37 was incorporated for its broad-spectrum antimicrobial properties, while pamidronate was included to inhibit bone resorption. The scaffold's porous structure, essential for cell infiltration and nutrient diffusion, was achieved through a freeze-drying process. In vitro assessments using SEM and FTIR confirmed the scaffold's morphology and chemical integrity. Antimicrobial efficacy was tested against pathogens of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa). In vivo studies in a murine model of infectious bone defect revealed the scaffold's effectiveness in reducing inflammation and bacterial load, and promoting bone regeneration. RNA sequencing of treated specimens provided insights into the molecular mechanisms underlying these observations, revealing significant gene expression changes related to bone healing and immune response modulation. The results indicate that the scaffold effectively inhibits bacterial growth and supports bone cell functions, making it a promising candidate for treating infectious bone defects. Future studies should focus on optimizing the release of therapeutic agents and evaluating the scaffold's clinical potential.
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Regeneración Ósea , Catelicidinas , Pseudomonas aeruginosa , Staphylococcus aureus , Andamios del Tejido , Regeneración Ósea/efectos de los fármacos , Andamios del Tejido/química , Animales , Ratones , Staphylococcus aureus/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/química , Difosfonatos/farmacología , Difosfonatos/química , Antiinfecciosos/farmacología , Antiinfecciosos/química , Durapatita/química , Durapatita/farmacología , Pamidronato/farmacología , Ingeniería de TejidosRESUMEN
Background: Osteomyelitis (OM) is an inflammatory condition of bone characterized by cortical bone devascularization and necrosis. Dysregulation of bone remodelling is triggered by OM. Bone remodelling is precisely coordinated by bone resorption and formation via a reversal phase. However, the cellular and molecular mechanisms underlying bone remodelling failure after osteomyelitis remain elusive. Methods: To elucidate the cellular and molecular mechanism underlying bone healing after osteomyelitis, we employed single-cell RNA sequencing (scRNA-seq) to depict the atlas of human cortical bone in normal, infected and reconstructed states. Dimensionality reduction by t-stochastic neighbourhood embedding (t-SNE) and graph-based clustering were applied to analyse the detailed clusters of osteoclast lineages. After trajectory analysis of osteoclast lineages over pseudotime, real-time PCR and immunofluorescence (IF) staining were applied to identify marker gene expression of various osteoclast lineages in the osteoclast induction model and human bone sections, respectively. The potential function and communication of osteoclasts were analysed via gene set enrichment analysis (GSEA) and CellChat. The chemotactic ability of mesenchymal stem cells (MSCs) and osteoclast lineage cells in various differentiation states was determined by transwell assays and coculture assays. The effects of various osteoclast lineages on the osteogenic differentiation potential of MSCs were also determined by using this coculture system. A normal mouse tibia fracture model and an osteomyelitis-related tibia fracture model were generated via injection of luciferase-labelled Staphylococcus aureus to verify the relationships between a novel osteoclast lineage and MSCs. Then, the infection was detected by a bioluminescence imaging system. Finally, immunofluorescence staining was used to detect the expression of markers of MSCs and novel osteoclast lineages in different remodelling phases in normal and infected bone remodelling models. Results: In this study, we constructed a cell atlas encompassing normal, infected, and reconstructed cortical bone. Then, we identified a novel subset at the earlier stage of the osteoclast lineage that exhibited increased expression of IDO1, CCL3, and CCL4. These IDO1highCCL3highCCL4high cells, termed osteostaticytes (OSCs), were further regarded as the reservoir of osteoclasts in the reversal phase. Notably, OSCs exhibited the highest chemotactic activity, surpassing other lineage subsets. We also discovered that cells at the earlier stage of the osteoclast lineage play a significant role in recruiting mesenchymal stem cells (MSCs). Finally, the data revealed that OSCs might be positively related to the occurrence of bone MSCs and the contribution of bone remodelling. Conclusion: Collectively, our findings revealed a novel stage (OSC) within the osteoclast lineage, potentially representing elusive bone reversal cells due to its increased chemotactic ability towards MSCs and potential contribution to bone remodelling. This study provides valuable insights into the intricate mechanisms of the reversal phase during bone remodelling and unveils potential therapeutic strategies for diseases associated with bone uncoupling. Translational potential of this article: This study identified a new subset, referred to as IDO1(plus symbol) CCL3(plus symbol) CCL4(plus symbol) osteostaticytes which displayed the highest chemotactic activity among all osteoclast lineages and may serve as reversal cells in bone remodelling. These findings offer new insights and insights for understanding bone reversal-related diseases and may serve as novel therapeutic targets for conditions such as osteomyelitis and delayed bone healing.
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Flatfoot is characterized by the collapse of the medial longitudinal arch, eversion of the rearfoot and abduction of the loaded forefoot. Orthopedic insoles are the frequently recommended treatment to support the arch of the foot, adjust the structure of the foot, reduce pain, improve stability and new techniques have been applied to the design of orthopedic insoles in recent years. However, the effectiveness of orthopedic insoles in different motions is still debated from the perspective of biomechanics. Therefore, this study aimed to explore the impact of orthopedic insoles on the kinematics and kinetics of lower limb motion, and to verify effectiveness and propose possible future research directions. We conducted a literature search across three databases employing Boolean operations and filtered results based on eligibility criteria. A total of 671 relevant literature were searched in this review, and 19 literature meeting the requirements were finally included. The results showed that: 1) orthopedic insoles were effective when patients walk, run and jump from the perspective of biomechanics; 2) orthopedic insoles had different result on the change of ankle sagittal angle, moment and peak pressure in the metatarsal region; 3) Whether the effect of insoles, which uses new techniques such as different 3D printed technologies and adds various accessories, can be further improved remains to be further studied; 4) Follow-up studies can pay more attention to the differences between diverse populations, increase the breadth of running and jumping and other movements research and long-term intervention.
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Background: The density of contrast medium in digital subtraction angiography (DSA) have been used to evaluate the cerebral circulation function. Our aim was to study the effect of difference in arteriovenous peak optical density (POD) after thrombectomy on functional outcomes. Methods: Consecutive patients with acute ischemic stroke due to large vessel occlusion who underwent thrombectomy were reviewed. We processed DSA images with ImageJ software to measure the POD of internal carotid artery (ICA) and cortical veins. The average POD of cortical veins (PODVA) and the POD difference between ICA and cortical veins (PODICA-CV) were calculated. Primary outcome was good functional outcome (modified Rankin scale score of 0-2 at 90 days). Results: One hundred sixty-six patients were finally included in the study. Patients with good functional outcome had lower ipsilateral PODVA (median [interquartile range (IQR)], 257.198 [216.623-296.631] vs. 290.944 [248.647-338.819], p < 0.001) and lower ipsilateral PODICA-CV (median [IQR], 128.463 [110.233-153.624] vs. 182.01 [146.621-211.331], p < 0.001). Multivariable logistic regression analyses showed that ipsilateral PODVA (odds ratio [OR] 0.991, 95% confidence interval [CI] 0.984-0.999, p = 0.019) and ipsilateral PODICA-CV (OR 0.975, 95% CI 0.963-0.986, p < 0.001) were associated with good functional outcome. The predictive ability was significantly enhanced in the model including ipsilateral PODICA-CV (0.893 vs. 0.842, p = 0.027). No correlation was found between ipsilateral PODICA-CV and expanded Thrombolysis in Cerebral Infarction grades (r = -0.133, p = 0.099). Conclusion: Ipsilateral PODICA-CV is an additional indicator of cerebral reperfusion status and predicts functional outcomes after thrombectomy.
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Peptidomics was employed to systematically analyze the characteristic peptides in Galli Gigerii Endothelium Corneum and its adulterants and establish a method for distinguishing Galli Gigerii Endothelium Corneum from its adulterants, including the gizzard membranes from ducks, geese, and pigeons. UPLC-Q-Exactive Orbitrap-MS was combined with multivariate statistical analysis to analyze the peptides in Galli Gigerii Endothelium Corneum and its adulterants. The structures of peptides were identified by pNovo combined with manual recognition of spectra, and synthetic peptide standards were used for validation. LC-MS/MS was used to optimize the sample pre-processing conditions, including the extraction procedure, extraction time, extraction solvents, and solvent volumes, for the characteristic peptide LESY in Galli Gigerii Endothelium Corneum. Multiple reaction monitoring(MRM) in the ESI~+ mode with m/z 511.24â269.11 and 511.24â243.13 as detection ions was employed for qualitative and quantitative analyses. The established UPLC-MS/MS method demonstrated good specificity, stability, and durability. The content of LESY in 16 batches of Galli Gigerii Endothelium Corneum samples ranged from 55.03 to 113.36 µg·g~(-1). Additionally, a qualitative detection method for the common peptide RDPVLVSR in adulterants was established with m/z 471.28â785.45 and 471.28â670.41 as the detection ions. This study established a convenient, rapid, and accurate detection method for the characteristic peptides in Galli Gigerii Endothelium Corneum and its adulterants. The method possesses good specificity, stability, and durability, providing a valuable reference for the identification and quality control of Galli Gigerii Endothelium Corneum and other traditional Chinese medicines derived from animal sources.
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Péptidos , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Animales , Cromatografía Líquida de Alta Presión/métodos , Péptidos/química , Péptidos/análisis , Endotelio/química , Pollos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Proteómica/métodos , Contaminación de Medicamentos , Cromatografía Líquida con Espectrometría de MasasRESUMEN
(1) This study examined the impact of fatigue and unanticipated factors on knee biomechanics during sidestep cutting and lateral shuffling in female basketball players, assessing the potential for non-contact anterior cruciate ligament (ACL) injuries. (2) Twenty-four female basketball players underwent fatigue induction and unanticipated change of direction tests, and kinematic and kinetic parameters were collected before and after fatigue with a Vicon motion capture system and Kistler ground reaction force (GRF) sensor. (3) Analysis using two-way repeated-measures ANOVA showed no significant interaction between fatigue and unanticipated factors on joint kinematics and kinetics. Unanticipated conditions significantly increased the knee joint flexion and extension angle (p < 0.01), decreased the knee flexion moment under anticipated conditions, and increased the knee valgus moment after fatigue (p ≤ 0.05). One-dimensional statistical parametric mapping (SPM1d) results indicated significant differences in GRF during sidestep cutting and knee inversion and rotation moments during lateral shuffling post-fatigue. (4) Unanticipated factors had a greater impact on knee load patterns, raising ACL injury risk. Fatigue and unanticipated factors were independent risk factors and should be considered separately in training programs to prevent lower limb injuries.
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Baloncesto , Articulación de la Rodilla , Humanos , Baloncesto/fisiología , Femenino , Fenómenos Biomecánicos/fisiología , Articulación de la Rodilla/fisiología , Adulto Joven , Lesiones del Ligamento Cruzado Anterior/fisiopatología , Adulto , Fatiga/fisiopatología , Rango del Movimiento Articular/fisiologíaRESUMEN
Objective: To review the existing literature on the application of computational fluid dynamics methods to study nasal particle deposition and to summarize and analyze the factors affecting nasal particle deposition in order to provide theoretical references for the development of future transnasal drug delivery devices and the prevention of respiratory-related diseases. Data Source: PubMed and CNKI databases. Methods: A search of all current literature (up to and including February 2023) was conducted. Search terms related to the topic of factors influencing nasal particle deposition were identified, and queries were conducted to identify relevant articles. Results: Both the properties of the particles themselves and the environmental conditions external to the particles can affect particle deposition in the nasal cavity, with particle deposition showing a positive correlation with particle size, particle density, and airflow velocity, with increasing subject age leading to a decrease in deposition, and with the relationship between airflow temperature and humidity still requiring more research to further explore. Conclusions: With the popularity of computational fluid dynamics, more and more scholars have applied computational fluid dynamics technology to explore the influence of different parameters on particle deposition. By summarizing and analyzing the influence law of various factors on deposition, it can provide a theoretical basis for the future development and application of transnasal drug delivery devices and the prevention of respiratory-related diseases, which makes a significant contribution to the optimization of clinical disease prevention and treatment. Level of Evidence: NA.
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AIM: To investigate ocular surface disorders and tear function changes in patients with acne vulgaris and explore the potential relationship between acne vulgaris and dry eye. METHODS: This cross-sectional study included right eyes of 53 patients with acne vulgaris and 54 healthy controls. The participants completed the Ocular Surface Disease Index (OSDI) questionnaire. The following ocular surface-related parameters were measured: tear meniscus height (TMH), noninvasive tear breakup time (NIBUT), Schirmer I test (SIT), lipid layer thickness (LLT) score of the tear film, meibum score, meibomian gland orifice obstruction score, the ratio of meibomian gland loss, conjunctival hyperemia score, and corneal fluorescein staining (CFS) score. RESULTS: The stability of the tear film decreased in acne vulgaris patients. In the acne group, the TMH and NIBUT were lower, whereas the OSDI, meibum score, meibomian gland orifice obstruction score, ratio of meibomian gland loss, and conjunctival hyperemia score were higher compared with controls (P<0.05). There were no significant differences in the CFS score, SIT, or LLT score between the groups (P>0.05). In two dry eye groups, the TMH, NIBUT, and LLT score were lower in the acne with dry eye (acne-DE) group, and the meibum score, meibomian gland orifice obstruction score, ratio of meibomian gland loss and conjunctival hyperemia score in the acne-DE group were higher (P<0.05). There were no significant differences between OSDI, SIT, and CFS score (P>0.05). CONCLUSION: Patients with moderate-to-severe acne vulgaris are more likely to experience dry eye than those without acne vulgaris. Reduced tear film stability and meibomian gland structure dysfunction are more pronounced in patients with moderate-to-severe acne and dry eye.
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OBJECTIVES: This study investigated the use of radiomics for diagnosing early-stage osteonecrosis of the femoral head (ONFH) by extracting features from multiple MRI sequences and constructing predictive models. MATERIALS AND METHODS: We conducted a retrospective review, collected MR images of early-stage ONFH (102 from institution A and 20 from institution B) and healthy femoral heads (102 from institution A and 20 from institution B) from two institutions. We extracted radiomics features, handled batch effects using Combat, and normalized features using z-score. We employed the Least absolute shrinkage and selection operator (LASSO) algorithm, along with Max-Relevance and Min-Redundancy (mRMR), to select optimal features for constructing radiomics models based on single, double, and multi-sequence MRI data. We evaluated performance using receiver operating characteristic (ROC) and precision-recall (PR) curves, and compared area under curve of ROC (AUC-ROC) values with the DeLong test. Additionally, we studied the diagnostic performance of the multi-sequence radiomics model and radiologists, compared the diagnostic outcomes of the model and radiologists using the Fisher exact test. RESULTS: We studied 122 early-stage ONFH and 122 normal femoral heads. The multi-sequence model exhibited the best diagnostic performance among all models (AUC-ROC, PR-AUC for training set: 0.96, 0.961; validation set: 0.96, 0.97; test set: 0.94, 0.94), and it outperformed three resident radiologists on the external testing group with an accuracy of 87.5 %, sensitivity of 85.00 %, and specificity of 90.00 % (p < 0.01), highlighting the robustness of our findings. CONCLUSIONS: Our study underscored the novelty of the multi-sequence radiomics model in diagnosing early-stage ONFH. By leveraging features extracted from multiple imaging sequences, this approach demonstrated high efficacy, indicating its potential to advance early diagnosis for ONFH. These findings provided important guidance for enhancing early diagnosis of ONFH through radiomics methods, offering new avenues and possibilities for clinical practice and patient care.
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Necrosis de la Cabeza Femoral , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Femenino , Masculino , Estudios Retrospectivos , Necrosis de la Cabeza Femoral/diagnóstico por imagen , Adulto , Persona de Mediana Edad , Algoritmos , Interpretación de Imagen Asistida por Computador/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Diagnóstico Precoz , RadiómicaRESUMEN
The endothelial glycocalyx (EG), covering the luminal side of endothelial cells, regulates vascular permeability and senses wall shear stress. In sepsis, EG undergoes degradation leading to increased permeability and edema formation. We hypothesized that restoring EG integrity using liposomal nanocarriers of preassembled glycocalyx (LNPG) will restore normal venular permeability in lipopolysaccharide (LPS)-induced sepsis model of mice. To test this hypothesis, we designed a unique perfusion microchamber in which the permeability of isolated venules could be assessed by measuring the concentration of Evans blue dye (EBD) in microliter samples of extravascular solution (ES). Histamine-induced time- and dose-dependent increases in EBD in the ES could be measured, confirming the sensitivity of the microchamber system. Notably, the histamine-induced increase in permeability was significantly attenuated by histamine receptor (H1) antagonist, triprolidine hydrochloride. Subsequently, mice were treated with LPS or LPS + LNPG. When compared with control mice, venules from LPS-treated mice showed a significant increased permeability, which was significantly reduced by LNPG administration. Moreover, in the presence of wall shear stress, intraluminal administration of LNPG significantly reduced the permeability in isolated venules from LPS-treated mice. We have found no sex differences. In conclusion, our newly developed microchamber system allows us to quantitatively measure the permeability of isolated venules. LPS-induced sepsis increases permeability of mesenteric venules that is attenuated by in vivo LNPG administration, which also reestablished endothelial responses to shear stress. Thus, LNPG presents a promising therapeutic potential for restoring EG function and thereby mitigating vasogenic edema due to increased permeability in sepsis.NEW & NOTEWORTHY In sepsis, the degradation of the endothelial glycocalyx leads to increased venular permeability. In this study, we developed a potentially new therapeutic approach by in vivo administration of liposomal nanocarriers of preassembled glycocalyx to mice, which restored venular sensitivity to wall shear stress and permeability in lipopolysaccharide-induced sepsis, likely by restoring the integrity of the endothelial glycocalyx. Using a new microchamber system, the permeability of Evans blue dye could be quantitatively determined.
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Permeabilidad Capilar , Glicocálix , Lipopolisacáridos , Liposomas , Sepsis , Estrés Mecánico , Animales , Glicocálix/metabolismo , Glicocálix/efectos de los fármacos , Permeabilidad Capilar/efectos de los fármacos , Lipopolisacáridos/toxicidad , Vénulas/metabolismo , Vénulas/fisiopatología , Vénulas/efectos de los fármacos , Masculino , Sepsis/fisiopatología , Sepsis/metabolismo , Sepsis/tratamiento farmacológico , Ratones , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Histamina/metabolismoRESUMEN
Using a curved carbon-fiber plate (CFP) in running shoes may offer notable performance benefit over flat plates, yet there is a lack of research exploring the influence of CFP geometry on internal foot loading during running. The objective of this study was to investigate the effects of CFP mechanical characteristics on forefoot biomechanics in terms of plantar pressure, bone stress distribution, and contact force transmission during a simulated impact peak moment in forefoot strike running. We employed a finite element model of the foot-shoe system, wherein various CFP configurations, including three stiffnesses (stiff, stiffer, and stiffest) and two shapes (flat plate (FCFP) and curved plate (CCFP)), were integrated into the shoe sole. Comparing the shoes with no CFP (NCFP) to those with CFP, we consistently observed a reduction in peak forefoot plantar pressure with increasing CFP stiffness. This decrease in pressure was even more notable in a CCFP demonstrating a further reduction in peak pressure ranging from 5.51 to 12.62%, compared to FCFP models. Both FCFP and CCFP designs had a negligible impact on reducing the maximum stress experienced by the 2nd and 3rd metatarsals. However, they greatly influenced the stress distribution in other metatarsal bones. These CFP designs seem to optimize the load transfer pathway, enabling a more uniform force transmission by mainly reducing contact force on the medial columns (the first three rays, measuring 0.333 times body weight for FCFP and 0.335 for CCFP in stiffest condition, compared to 0.373 in NCFP). We concluded that employing a curved CFP in running shoes could be more beneficial from an injury prevention perspective by inducing less peak pressure under the metatarsal heads while not worsening their stress state compared to flat plates.
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Carrera , Zapatos , Carrera/fisiología , Humanos , Fenómenos Biomecánicos , Presión , Fibra de Carbono/química , Antepié Humano/fisiología , Análisis de Elementos Finitos , Estrés Mecánico , Soporte de Peso/fisiología , Carbono/química , Diseño de Equipo , Pie/fisiologíaRESUMEN
The orientation-guidance coupled with in-situ activation methodology is developed to synthesize the N-doped porous carbon (NPC) with well-developed porosity and high specific surface area, using coal pitch as a carbon precursor. The orientation-guidance and activation are dedicated to generating microporous and mesoporous channels, respectively. The in-situ N incorporation into the carbon skeleton is realized along with the formation of porous carbon (PC), ensuring the uniformity of N doping. As an electrode material of supercapacitor, benefiting from the robust hexagon-like building block decorated with micro-mesoporous channels and N doping, NPC electrode affords a significant improvement in capacitive energy-storage performance, achieving a specific capacitance of up to 333F g-1 at 1 A/g, which far exceeds those of PC and activated carbon. Notably, even under high mass loading of 10 mg cm-2, the NPC maintains a satisfactory capacitance of 258F g-1 at 1 A/g. When employed as the anode in Li-ion capacitor (LIC), apart from exhibiting enhanced anode behavior compared to graphite anode, NPC also delivers exceptional cyclability. Furthermore, density functional theory calculations have validated the enhanced electrical conductivity and Li storage ability contributed by N doping, providing a theoretical foundation for the observed improvements in electrochemical performance. A full LIC configured with NPC anode delivers extraordinary Ragone performance and outstanding cyclability. This work also proposes a feasible way to realize the oriented conversion of coal pitch into high-performance electrode materials for electrochemical energy-storage devices.