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Turbulent bursting events have been classified into outward interactions (Q1), ejections (Q2), inward interactions (Q3), and sweeps (Q4) in various studies. Ejections (Q2) and sweeps (Q4) have been identified as significant contributors to time consumption, momentum flux, and sediment flux. Additionally, research has shown that the distribution of these events varies nonuniformly at different bed elevations. Despite extensive investigations into the nonuniform distribution of turbulent bursting events, their impact on sediment transport has been rarely explored. In this work, we developed a modified stochastic diffusion particle tracking model (SD-PTM) driven by skew Brownian motion (SBM) using the stochastic Lagrangian approach to scrutinize sediment particle movement in turbulent flows. The model incorporates turbulent characteristics derived from a direct numerical simulation dataset, allowing for a comprehensive analysis of sediment particle dynamics. Moreover, the proposed model accounts for the nonuniform spatial distribution of ejection and sweep events, as well as the particle movement direction during these events. Numerical simulations of the model were conducted to trace sediment particle trajectories in the streamwise and vertical directions. The analysis of sediment transport involved calculating the variance of particle trajectories to examine anomalous diffusion. The model's performance was evaluated by comparing it with flow velocity and sediment concentration profiles obtained from measurements in previous studies. In conclusion, our study suggests that the motion of sediment particles in turbulent flow can be thoroughly investigated under extreme flow conditions using the modified SD-PTM driven by SBM.
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Synthetic polymer nanoparticles (NPs) with biomimetic properties are ideally suited for different biomedical applications such as drug delivery and direct therapy. However, bulk synthetic approaches can suffer from poor reproducibility and scalability when precise size control or multi-step procedures are required. Herein, we report an integrated microfluidic chip for the synthesis of polymer NPs. The chip could sequentially perform homopolymer synthesis and subsequent crosslinking into NPs without intermediate purification. This was made possible by fabrication of the chip with a fluorinated elastomer and incorporation of two microfluidic mixers. The first was a long channel with passive mixing features for the aqueous RAFT synthesis of stimuli-responsive polymers in ambient conditions. The polymers were then directly fed into a hydrodynamic flow focusing (HFF) junction that rapidly mixed them with a crosslinker solution to produce NPs. Compared to microfluidic systems made of PDMS or glass, our chip had better compatibility and facile fabrication. The polymers were synthesized with high monomer conversion and the NP size was found to be influenced by the flow rate ratio between the crosslinker solution and polymer solution. This allowed for the size to be predictably controlled by careful adjustment of the fluid flow rates. The size of the NPs and their stimuli-responses were studied using DLS and SEM imaging. This microfluidic chip design can potentially streamline and provide some automation for the bottom-up synthesis of polymer NPs while offering on-demand size control.
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Graft-versus-host disease (GVHD) is one of the major complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which seriously affects the prognosis of patients. At present, a new regimen of post-transplantation cyclophosphamide (PTCy) combined with antithymocyte globulin (ATG) has been used to prevent GVHD, indicating that PTCy combined with ATG may have a good effect on the prevention of GVHD in different types of transplantation. However, the mechanism of this regimen, its effect on immune reconstitution and viral reactivation still needs to be further studied. Therefore, this article briefly reviews the research progress of PTCy combined with ATG in preventing GVHD after HSCT.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Soro Antilinfocitário , Ciclofosfamida , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante Homólogo , Estudos RetrospectivosRESUMO
OBJECTIVE: To assess the added value of contrast-enhanced ultrasound (CEUS) to conventional ultrasound in differentiating benign soft-tissue tumors from malignant ones. METHODS: 197 soft-tissue tumors underwent ultrasound examination with confirmed histopathology were retrospectively evaluated. The radiologists classified all the tumors as benign, malignant, or indeterminate according to ultrasound features. The indeterminate tumors underwent CEUS were reviewed afterwards for malignancy identification by using individual and combined CEUS features. RESULTS: Ultrasound analysis classified 62 soft-tissue tumors as benign, 111 tumors as indeterminate and 24 tumors as malignant. There 104 indeterminate tumors were subject to CEUS. Three CEUS features including enlargement of enhancement area, infiltrative enhancement boundary, and intratumoral arrival time difference were significantly associated with the tumor nature in both univariable and multivariable analysis for the indeterminate tumors (all p < 0.05). When at least one out of the three discriminant CEUS features were present, the best sensitivity of 100% for malignancy identification was obtained with the specificity of 66.7% and the AUC of 0.833. When at least two of the three discriminant CEUS features were present, the best area under the receiver operating characteristic curve (AUC) of 0.924 for malignancy identification was obtained. The combination of at least two discriminant CEUS features showed much better diagnostic performance than the optimal combination of ultrasound features in terms of AUC (0.924 vs 0.608, p < 0.0001), sensitivity (94.0% vs 42.0%, p < 0.0001), and specificity (90.7% vs 79.6%, p = 0.210) for the indeterminate tumors. CONCLUSION: The combination CEUS features of enlargement of enhancement area, infiltrative enhancement boundary and intratumoral arrival time difference are valuable to improve the discriminating performance for indeterminate soft-tissue tumors on conventional ultrasound. ADVANCES IN KNOWLEDGE: The combination of peritumoral and arrival-time CEUS features can improve the discriminating performance for indeterminate soft-tissue tumors on conventional ultrasound.
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Meios de Contraste , Neoplasias de Tecidos Moles , Humanos , Estudos Retrospectivos , Ultrassonografia , Curva ROC , Neoplasias de Tecidos Moles/diagnóstico por imagem , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To evaluate the effectiveness of contrast-enhanced ultrasound (CEUS) guided core needle biopsy (CNB) in diagnosing soft tissue tumors (STTs) and to identify the conventional ultrasonography (US) features of STTs that are recommended for CEUS-guided CNB. MATERIALS AND METHODS: A retrospective study was conducted on 123 patients with surgically confirmed STTs. Before surgeries, all subjects underwent CNB under the guidance of US or CEUS. The histopathological results of surgical specimens were considered as the gold standards. A successful biopsy diagnosis was defined as the pathological subtypes obtained by biopsy consistent with the gold standard. The diagnostic yields were compared between the US and CEUS groups, and the diagnostic yields based on various conventional US features of STTs were also compared between the two groups. RESULTS: Sixty-seven cases underwent US-guided CNB and fifty-six cases underwent CEUS-guided CNB. The clinical, biopsy, and conventional US characteristics revealed no significant difference between the two groups. The diagnostic yield of the CEUS group was statistically higher than that of the US group (p = 0.011). In the CEUS group, more STTs with the anechoic areas were identified after CEUS examination (p = 0.031). Furthermore, the diagnostic yields based on the conventional US features of STTs, including deep fascia layer (p = 0.010), a maximum diameter ≥5 cm (p = 0.037), rough margin (p = 0.016), heterogeneous echotexture (p = 0.017), and absence of anechoic area (p = 0.013), were significantly different between the two groups, and the CEUS group exhibited higher diagnostic yields. CONCLUSION: CEUS-guided CNB was found to be an efficient method for STTs diagnosis. It is particularly recommended for STTs with the following conventional US features, including location in deep fascia layer, a maximum diameter ≥5 cm, rough margin, heterogeneous echotexture, or absence of anechoic area.
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Biópsia Guiada por Imagem , Neoplasias de Tecidos Moles , Humanos , Biópsia com Agulha de Grande Calibre/métodos , Estudos Retrospectivos , Sensibilidade e Especificidade , Ultrassonografia/métodos , Biópsia Guiada por Imagem/métodos , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/patologia , Meios de Contraste , Ultrassonografia de IntervençãoRESUMO
Purpose: To evaluate the diagnostic yield of ultrasonography (US)-guided core needle biopsy (CNB) in the diagnosis of soft tissue tumors (STTs) and to analyze the failure factors. Methods: 139 patients with STTs that underwent both US-guided CNB and surgical resection were collected retrospectively. Compared with the histopathological results of surgical resection, the biopsy failure was defined as the following conditions: indefinitive diagnosis, including insufficient samples and unknown subtypes with correct biological potential classification; wrong diagnosis, including wrong biological potential classification and wrong subtypes with correct biological potential classification. Univariate and multivariate analyses from the perspectives of histopathological, demographic and US features together with biopsy procedures were performed to determine risk factors for diagnostic failure. Results: The diagnostic yield of US-guided CNB for STTs in our study was 78.4%, but when only considering the correct biological potential classification of STTs, the diagnostic yield was 80.6%. The multivariate analysis showed that adipocytic tumors (odds ratio (OR) = 10.195, 95% confidence interval (CI): 1.062 - 97.861, p = 0.044), vascular tumors (OR = 41.710, 95% CI: 3.126 - 556.581, p = 0.005) and indeterminate US diagnosis (OR = 8.641, 95% CI: 1.852 - 40.303, p = 0.006) were correlated with the diagnostic failure. The grade III vascular density (OR = 0.019, 95% CI: 0.001 - 0.273, p = 0.007) enabled a higher diagnostic accuracy. Conclusion: US-guided CNB can be an effective modality for the diagnosis of STTs. The diagnostic yield can be increased when the tumor vascular density was grade III in Color Doppler US, but can be decreased in adipocytic tumors, vascular tumors and masses with indeterminate US diagnosis.
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Obstructive sleep apnea (OSA) is a sleep-related breathing disorder characterized by intermittent and recurrent upper airway collapse during sleep that leads to chronic intermittent hypoxia (CIH). The genioglossus (GG) is the largest dilator muscle, which controls the upper airway and plays an important role in OSA pathology. Elucidating its genetic alterations may help identify potential targets for OSA. However, the genetic aspects of the GG in CIH mice remain unclear. Here, we have conducted an RNA sequencing (RNA-Seq) analysis to assess the differentially expressed genes (DEGs) in the GG between CIH mice and normoxia (NOR) mice. A total of 637 DEGs were identified to be dysregulated in CIH mice compared with control mice. Bioinformatics analysis showed that the DEGs were related to various physiological processes, such as the endogenous stimulus responses, cellular component organization and metabolic processes. Extracellular matrix (ECM)-receptor interaction was the top KEGG pathway in the environmental information processing category with high significance and large fold changes. From the gene weight distributions of collagen (Col)-related biological processes (BPs), we found several significant DEGs, such as Col1a1, Col1a2, Mmp2, Col3a1, Col5a1, Fmod, and Col5a2. A PPI network showed that Col1a1 was linked to ECM-receptor interactions, responses to reactive oxygen species (ROS) and Col-related BPs. It was verified in vivo and in vitro that hypoxia can induce excess ROS and reduce Col expression levels. Moreover, we found NAC can effectively scavenge ROS and restore collagen synthesis. These findings contribute to a better understanding of the mechanisms linking OSA and upper airway muscle injury and may help identify potential therapeutic targets.
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Apneia Obstrutiva do Sono , Transcriptoma , Camundongos , Animais , Espécies Reativas de Oxigênio/metabolismo , Hipóxia , FibromodulinaRESUMO
OBJECTIVE: To clarify the expression of Bcl-2 and Bax following forward mandibular positioning (FMP) in the condylar chondrocytes of rabbits. MATERIALS AND METHODS: Sixty rabbits at 8 weeks of age were randomly allocated to the experimental group (n = 36) and control group (n = 24). Rabbits in the experimental group were induced to FMP by a functional appliance. Six rabbits from the experimental group and four from the control group were sacrificed after 3 days and 1, 2, 4, 8, and 12 weeks, respectively. All the right temporomandibular joints (TMJs) were collected and the expression of Bcl-2 and Bax was evaluated by immunohistochemical staining. RESULTS: The results showed the expression pattern of Bcl-2 and Bax during 12 weeks after FMP. The expression of Bcl-2 reached the highest level at 1 week, whereas Bax reached its maximal expression after 4 weeks. Subsequently, the expression of Bcl-2 and Bax gradually decreased. The ratio of Bcl-2/Bax began to decrease 3 days after FMP and continued to decline until 12 weeks. CONCLUSIONS: FMP with functional appliances could change the expression of Bcl-2 and Bax, which is related to apoptosis in condylar chondrocytes.
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Condrócitos/patologia , Avanço Mandibular/métodos , Côndilo Mandibular/patologia , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteína X Associada a bcl-2/análise , Animais , Calcificação Fisiológica/fisiologia , Proliferação de Células , Feminino , Regulação da Expressão Gênica , Hipertrofia , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Masculino , Avanço Mandibular/instrumentação , Microscopia de Vídeo , Aparelhos Ortodônticos Funcionais , Coelhos , Distribuição Aleatória , Articulação Temporomandibular/patologia , Fatores de TempoRESUMO
OBJECTIVE: This study was designed to evaluate the combined effects of intermittent hydrostatic pressure (IHP) and TGF-ß1 or TNF-α on proteoglycan4 (PRG4) expression in rat temporomandibular synovial fibroblasts (SFs). STUDY DESIGN: Rat SFs were isolated and expanded in monolayer cultures and subjected to IHP in the presence of TGF-ß1 or TNF-α. Quantitative real-time RT-PCR was applied to analyze the PRG4 expression levels. Enzyme-linked immunosorbent assay was also used for the quantification of PRG4 accumulation in the culture medium while immunofluorescence staining was used to detect intracellular PRG4 protein expression. RESULTS: The combination of IHP and TGF-ß1 induced greater PRG4 expression than either stimulus alone. In contrast, TNF-α inhibited PRG4 expression, and this was partially alleviated by IHP. CONCLUSIONS: Our study demonstrates a beneficial role of IHP, which can be used successfully in combination with TGF-ß1 to enhance PRG4 production, and can partially counteract TNF-α-induced PRG4 inhibition in isolated rat SFs.
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Pressão Hidrostática , Proteoglicanas/biossíntese , Articulação Temporomandibular/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Masculino , Proteoglicanas/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley , Estresse Mecânico , Membrana Sinovial/citologia , Articulação Temporomandibular/citologia , Fator de Crescimento Transformador beta1/administração & dosagem , Fator de Necrose Tumoral alfa/administração & dosagemRESUMO
OBJECTIVE: To investigate the role of apoptosis in the remodeling of temporomandibular joint (TMJ) under pressure. METHODS: Synovial fibroblasts obtained from rat temporomandibular joint were subjected to different hydrostatic pressure for 12 h. Changes of ultrastructure were observed by transmission electron microscope. RESULTS: At 30 kPa, the ultrastructure of synovial fibroblasts showed no obvious changes. At 60 kPa, the chromatin was condensated, the baryon took on crescent and the mitochondria seemed varicose. At 90 kPa, the apoptosis-like body was wrapped by membrane and embedded in the high density chromatin. CONCLUSIONS: Apoptosis-like change took place in ultrastructure of synovial fibroblasts under hydrostatic pressure, and the degree of the change was related to the hydrostatic pressure exerted.