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1.
J Investig Med ; : 10815589241246541, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557364

RESUMO

Ferroptosis is a recently identified and evolutionarily conserved form of programmed cell death. This process is initiated by an imbalance in iron metabolism, leading to an overload of ferrous ions. These ions promote lipid peroxidation in the cell membrane through the Fenton reaction. As the cell's antioxidant defenses become overwhelmed, a fatal build-up of reactive oxygen species (ROS) occurs, resulting in the rupture of the plasma membrane. Ferroptosis is implicated in conditions such as ischemia-reperfusion injuries and a range of cancers. In our research, we explored ferroptosis in myelodysplastic syndromes (MDS) by measuring iron levels, transferrin receptor expression, and glutathione peroxidase 4 (GPX4) mRNA. Our findings revealed that MDS patients had significantly higher Fe2+ levels in CD33+ cells and increased transferrin receptor mRNA compared to healthy individuals. GPX4 expression was also higher in MDS, but not statistically significant. To investigate potential treatments for myeloid hematological diseases through ferroptosis induction, we treated the myelodysplastic syndrome cell line (SKM-1) and two myeloid leukemia cell lines (KG-1 and K562) with erastin, an iron transfer inducer. We observed that erastin treatment led to glutathione depletion, reduced GPX4 activity, and increased ROS, culminating in cell death by ferroptosis. Furthermore, combining erastin with azacitidine demonstrated a synergistic effect on MDS and leukemia cell lines, suggesting a promising approach for treating these hematological conditions with this drug combination. Our experiments confirm erastin's ability to induce ferroptosis in MDS and highlight its potential synergistic use with azacitidine for treatment.

2.
Orthod Craniofac Res ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581082

RESUMO

OBJECTIVES: To propose a method for evaluating the coordination of maxillomandibular alveolar arch in transverse dimension with cone-beam computed tomography (CBCT) and to apply this method to subjects with normal occlusion at different dentition stages or transverse discrepancy. MATERIALS AND METHODS: Digital data of 130 patients with normal occlusion at different dentition stages or transverse discrepancy were collected for three-dimensional reconstruction. The patients with normal occlusion were divided into Group 1 (>16 years) and Group 2 (≤16 years) based on their age. Adult patients with posterior crossbite were divided into the Group 3. According to the proposed method, the average alveolar arch coordination angle (AACA) and other parameters were analysed in each group. Group 1 was considered as the control group and compared with Group 2 and Group 3. RESULTS: Significant differences were observed in the maxillary posterior segment width among patients with normal occlusion. Group 3 demonstrated increased AACA and mandibular alveolar arch width compared with the normal occlusion group. Pearson correlation analysis indicated a positive relationship between maxillomandibular alveolar arch widths in the normal occlusion groups, with a strong correlation between AACA and the disparity in maxillomandibular widths. CONCLUSION: Adults with normal occlusion exhibit significantly wider maxillary posterior alveolar arches than adolescents, with no marked difference in mandibular widths. The posterior crossbite group showed broader mandibular alveolar arches. There was a strong correlation between AACA and the difference in maxillomandibular widths. This study's method shows potential value for orthodontic transverse diagnosis.

3.
Tissue Cell ; 88: 102358, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38537379

RESUMO

OBJECTIVE: With the growing interest in the role of fibroblasts in osteogenesis, this study presents a comparative evaluation of the osteogenic potential of fibroblasts derived from three distinct sources: human gingival fibroblasts (HGFs), mouse embryonic fibroblasts (NIH3T3 cells), and mouse subcutaneous fibroblasts (L929 cells). MC3T3-E1 pre-osteoblast cells were employed as a positive control for osteogenic behavior. DESIGN: Our assessment involved multiple approaches, including vimentin staining for cell origin verification, as well as ALP and ARS staining in conjunction with RT-PCR for osteogenic characterization. RESULTS: Our findings revealed the superior osteogenic differentiation capacity of HGFs compared to MC3T3-E1 and NIH3T3 cells. Analysis of ALP staining confirmed that early osteogenic differentiation was most prominent in MC3T3-E1 cells at 7 days, followed by NIH3T3 and HGFs. However, ARS staining at 21 days demonstrated that HGFs produced the highest number of calcified nodules, indicating their robust potential for late-stage mineralization. This late-stage osteogenic potential of HGFs was further validated through RT-PCR analysis. In contrast, L929 cells displayed no significant osteogenic differentiation potential. CONCLUSIONS: In light of these findings, HGFs emerge as the preferred choice for seed cells in bone tissue engineering applications. This study provides valuable insights into the potential utility of HGFs in the fields of bone tissue engineering and regenerative medicine.

4.
Sensors (Basel) ; 24(6)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38544140

RESUMO

Long-span bridges are susceptible to damage, aging, and deformation in harsh environments for a long time. Therefore, structural health monitoring (SHM) systems need to be used for reasonable monitoring and maintenance. Among various indicators, bridge displacement is a crucial parameter reflecting the bridge's health condition. Due to the simultaneous bearing of multiple environmental loads on suspension bridges, determining the impact of different loads on displacement is beneficial for the better understanding of the health conditions of the bridges. Considering the fact that extreme gradient boosting (XGBoost) has higher prediction performance and robustness, the authors of this paper have developed a data-driven approach based on the XGBoost model to quantify the impact between different environmental loads and the displacement of a suspension bridge. Simultaneously, this study combined wavelet threshold (WT) denoising and the variational mode decomposition (VMD) method to conduct a modal decomposition of three-dimensional (3D) displacement, further investigating the interrelationships between different loads and bridge displacements. This model links wind speed, temperature, air pressure, and humidity with the 3D displacement response of the span using the bridge monitoring data provided by the GNSS and Earth Observation for Structural Health Monitoring (GeoSHM) system of the Forth Road Bridge (FRB) in the United Kingdom (UK), thus eliminating the temperature time-lag effect on displacement data. The effects of the different loads on the displacement are quantified individually with partial dependence plots (PDPs). Employing testing, it was found that the XGBoost model has a high predictive effect on the target variable of displacement. The analysis of quantification and correlation reveals that lateral displacement is primarily affected by same-direction wind, showing a clear positive correlation, and vertical displacement is mainly influenced by temperature and exhibits a negative correlation. Longitudinal displacement is jointly influenced by various environmental loads, showing a positive correlation with atmospheric pressure, temperature, and vertical wind and a negative correlation with longitudinal wind, lateral wind, and humidity. The results can guide bridge structural health monitoring in extreme weather to avoid accidents.

5.
Int J Biol Macromol ; 262(Pt 1): 129927, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38311130

RESUMO

To promote bone repair, it is desirable to develop three-dimensional multifunctional fiber scaffolds. The densely stacked and tightly arranged conventional two-dimensional electrospun fibers hinder cell penetration into the scaffold. Most of the existing three-dimensional structural materials are isotropic and monofunctional. In this research, a Janus nanofibrous scaffold based on silk fibroin/polycaprolactone (SF/PCL) was fabricated. SF-encapsulated SeNPs demonstrated stability and resistance to aggregation. The outside layer (SF/PCL/Se) of the Janus nanofiber scaffold displayed a structured arrangement of fibers, facilitating cell growth guidance and impeding cell invasion. The inside layer (SF/PCL/HA) featured a porous structure fostering cell adhesion. The Janus fiber scaffold containing SeNPs notably suppressed S. aureus and E. coli activities, correlating with SeNPs concentration. In vitro, findings indicated considerable enhancement in alkaline phosphatase (ALP) activity of MC3T3-E1 osteoblasts and upregulation of genes linked to osteogenic differentiation with exposure to the SF/PCL/HA/Se Janus nanofibrous scaffold. Moreover, in vivo, experiments demonstrated successful critical bone defect repair in mouse skulls using the SF/PCL/HA/Se Janus nanofiber scaffold. These findings highlight the potential of the SF/PCL-based Janus nanofibrous scaffold, integrating SeNPs and nHA, as a promising biomaterial in bone tissue engineering.


Assuntos
Fibroínas , Nanofibras , Camundongos , Animais , Fibroínas/farmacologia , Fibroínas/química , Tecidos Suporte/química , Osteogênese , Porosidade , Escherichia coli , Staphylococcus aureus , Engenharia Tecidual/métodos , Poliésteres/química , Regeneração Óssea , Nanofibras/química , Seda/química
6.
Proc Natl Acad Sci U S A ; 121(6): e2313092121, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38300870

RESUMO

Root development is tightly controlled by light, and the response is thought to depend on signal transmission from the shoot. Here, we show that the root apical meristem perceives light independently from aboveground organs to activate the light-regulated transcription factor ELONGATED HYPOCOTYL5 (HY5). The ROS balance between H2O2 and superoxide anion in the root is disturbed under darkness with increased H2O2. We demonstrate that root-derived HY5 directly activates PER6 expression to eliminate H2O2. Moreover, HY5 directly represses UPBEAT1, a known inhibitor of peroxidases, to release the expression of PERs, partially contributing to the light control of ROS balance in the root. Our results reveal an unexpected ability in roots with specific photoreception and provide a mechanistic framework for the HY5-mediated interaction between light and ROS signaling in early root development.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Peróxido de Hidrogênio/metabolismo , Luz , Regulação da Expressão Gênica de Plantas
7.
J Colloid Interface Sci ; 662: 1063-1074, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38369419

RESUMO

Polyacrylamide (PAM) hydrogels have garnered significant attention due to their unique swelling properties, biocompatibility, and stability, resulting in them being promising candidates for various applications, ranging from drug delivery to tissue engineering. However, traditional PAM hydrogels suffer from low strength and poor toughness, which limits their widespread use. In this study, based on the theory of filler-reinforced composites, we introduced ordered sulfonated polystyrene (SPS) particles into PAM hydrogels using electric field-assisted techniques. The effects of the geometric dimensions and filling concentration of SPS particles on thermal stability, swelling/deswelling behavior, and mechanical properties of composite hydrogels were investigated. When filled with ordered 100 nm SPS particles at a concentration of 2.0 g·L-1, the resulting SPS/PAM composite exhibited improved water retention capacity, as well as a fracture elongation of 316 % and a tensile strength of 23 kPa. These findings in the paper provide valuable insights into the understanding of PAM hydrogels and open up new avenues for the development of advanced hydrogel-based systems with enhanced performance and functionality.

8.
Cell Metab ; 36(3): 598-616.e9, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38401546

RESUMO

Thrombosis represents the leading cause of death and disability upon major adverse cardiovascular events (MACEs). Numerous pathological conditions such as COVID-19 and metabolic disorders can lead to a heightened thrombotic risk; however, the underlying mechanisms remain poorly understood. Our study illustrates that 2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with MACEs. 2MBC enhances platelet hyperreactivity and thrombus formation in mice. Mechanistically, 2MBC binds to integrin α2ß1 in platelets, potentiating cytosolic phospholipase A2 (cPLA2) activation and platelet hyperresponsiveness. Genetic depletion or pharmacological inhibition of integrin α2ß1 largely reverses the pro-thrombotic effects of 2MBC. Notably, 2MBC can be generated in a gut-microbiota-dependent manner, whereas the accumulation of plasma 2MBC and its thrombosis-aggravating effect are largely ameliorated following antibiotic-induced microbial depletion. Our study implicates 2MBC as a metabolite that links gut microbiota dysbiosis to elevated thrombotic risk, providing mechanistic insight and a potential therapeutic strategy for thrombosis.


Assuntos
COVID-19 , Microbioma Gastrointestinal , Trombose , Humanos , Camundongos , Animais , Integrina alfa2beta1/genética , Integrina alfa2beta1/metabolismo , Colágeno/metabolismo , Plaquetas/metabolismo , COVID-19/metabolismo
9.
Acta Biomater ; 176: 432-444, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38185232

RESUMO

The use of bone substitute materials is crucial for the healing of large bone defects. Immune response induced by bone substitute materials is essential in bone regeneration. Prior research has mainly concentrated on innate immune cells, such as macrophages. Existing research suggests that T lymphocytes, as adaptive immune cells, play an indispensable role in bone regeneration. However, the mechanisms governing T cell recruitment and specific subsets that are essential for bone regeneration remain unclear. This study demonstrates that CD4+ T cells are indispensable for ectopic osteogenesis by biphasic calcium phosphate (BCP). Subsequently, the recruitment of CD4+ T cells is closely associated with the activation of calcium channels in macrophages by BCP to release chemokines Ccl3 and Ccl17. Finally, these recruited CD4+ T cells are predominantly Tregs, which play a significant role in ectopic osteogenesis by BCP. These findings not only shed light on the immune-regenerative process after bone substitute material implantation but also establish a theoretical basis for developing bone substitute materials for promoting bone tissue regeneration. STATEMENT OF SIGNIFICANCE: Bone substitute material implantation is essential in the healing of large bone defects. Existing research suggests that T lymphocytes are instrumental in bone regeneration. However, the specific mechanisms governing T cell recruitment and specific subsets that are essential for bone regeneration remain unclear. In this study, we demonstrate that activation of calcium channels in macrophages by biphasic calcium phosphate (BCP) causes them to release the chemokines Ccl3 and Ccl17 to recruit CD4+ T cells, predominantly Tregs, which play a crucial role in ectopic osteogenesis by BCP. Our findings provide a theoretical foundation for developing bone substitute material for bone tissue regeneration.


Assuntos
Substitutos Ósseos , Substitutos Ósseos/farmacologia , Regeneração Óssea , Hidroxiapatitas/farmacologia , Canais de Cálcio , Quimiocinas , Osteogênese , Fosfatos de Cálcio/farmacologia
10.
Signal Transduct Target Ther ; 9(1): 17, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38212307

RESUMO

Although stem cell-based therapy has demonstrated considerable potential to manage certain diseases more successfully than conventional surgery, it nevertheless comes with inescapable drawbacks that might limit its clinical translation. Compared to stem cells, stem cell-derived exosomes possess numerous advantages, such as non-immunogenicity, non-infusion toxicity, easy access, effortless preservation, and freedom from tumorigenic potential and ethical issues. Exosomes can inherit similar therapeutic effects from their parental cells such as embryonic stem cells and adult stem cells through vertical delivery of their pluripotency or multipotency. After a thorough search and meticulous dissection of relevant literature from the last five years, we present this comprehensive, up-to-date, specialty-specific and disease-oriented review to highlight the surgical application and potential of stem cell-derived exosomes. Exosomes derived from stem cells (e.g., embryonic, induced pluripotent, hematopoietic, mesenchymal, neural, and endothelial stem cells) are capable of treating numerous diseases encountered in orthopedic surgery, neurosurgery, plastic surgery, general surgery, cardiothoracic surgery, urology, head and neck surgery, ophthalmology, and obstetrics and gynecology. The diverse therapeutic effects of stem cells-derived exosomes are a hierarchical translation through tissue-specific responses, and cell-specific molecular signaling pathways. In this review, we highlight stem cell-derived exosomes as a viable and potent alternative to stem cell-based therapy in managing various surgical conditions. We recommend that future research combines wisdoms from surgeons, nanomedicine practitioners, and stem cell researchers in this relevant and intriguing research area.


Assuntos
Exossomos , Células-Tronco Pluripotentes Induzidas , Células-Tronco Mesenquimais , Exossomos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Embrionárias
11.
Insect Mol Biol ; 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238257

RESUMO

Paired box (Pax) genes are highly conserved throughout evolution, and the Pax protein is an important transcription factor of embryonic development. The Pax gene Bmgsb is expressed in the silk glands of silkworm, but its biological functions remain unclear. This study aimed to investigate the expression pattern of Bmgsb in the silk gland and explore its functions using RNA interference (RNAi). Here, we identified eight Pax genes in Bombyx mori. Phylogenetic analysis showed that the B. mori Pax genes were highly homologous to the Pax genes in other insects and highly evolutionarily conserved. The tissue expression profile showed that Bmgsb was expressed in the anterior silk gland and anterior part of the middle silk gland (AMSG). RNAi of Bmgsb resulted in defective development of the AMSG, and the larvae were mostly unable to cocoon in the wandering stage. RNA-seq analysis showed that the fibroin genes fib-l, fib-h and p25, cellular heat shock response-related genes and phenol oxidase genes were considerably upregulated upon Bmgsb knockdown. Furthermore, quantitative reverse transcription-PCR results showed that the fibroin genes and ubiquitin proteolytic enzyme-related genes were significantly upregulated in the AMSG after Bmgsb knockdown. This study provides a foundation for future research on the biological functions of B. mori Pax genes. In addition, it demonstrates the important roles of Bmgsb in the transcriptional regulation of fibroin genes and silk gland development.

12.
IEEE Trans Image Process ; 33: 840-855, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38224515

RESUMO

Cross-domain (CD) hyperspectral image classification (HSIC) has been significantly boosted by methods employing Few-Shot Learning (FSL) based on CNNs or GCNs. Nevertheless, the majority of current approaches disregard the prior information of spectral coordinates with limited interpretability, leading to inadequate robustness and knowledge transfer. In this paper, we propose an asymmetric encoder-decoder architecture, Spectral Coordinate Transformer (SCFormer), for the CDFSL HSIC task. Several dense Spectral Coordinate blocks (SC blocks) are embedded in the backbone of the encoder to establish feature representation with better generalization, which integrates spectral coordinates via Rotary Position Embedding (RoPE) to minimize spectral position disturbance caused by the convolution operation. Due to a large amount of hyperspectral image data and the high demand for model generalization ability in cross-domain scenarios, we design two mask patterns (Random Mask and Sequential Mask) built on unexploited spectral coordinates within the SC blocks, which are unified with the asymmetric structure to learn high-capacity models efficiently and effectively with satisfactory generalization. Besides, from the perspective of the loss function, we devise an intra-domain loss function founded on the Orthogonal Complement Space Projection (OCSP) theory to facilitate the aggregation of samples in the metric space, which promotes intra-domain consistency and increases interpretability. Finally, the strengthened class expression capacity of the intra-domain loss function contributes to the inter-domain loss function constructed by Wasserstein Distance (WD) for realizing domain alignment. Experimental results on four benchmark data sets demonstrate the superiority of the SCFormer.

13.
Micromachines (Basel) ; 15(1)2024 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-38258225

RESUMO

Ceramic matrix composites have the advantages of low density, high specific strength, high specific die, high-temperature resistance, wear resistance, chemical corrosion resistance, etc., which are widely used in aerospace, energy, transportation, and other fields. CMCs have become an important choice for engine components and other high-temperature component manufacturing. However, ceramic matrix composite is a kind of multi-phase structure, anisotropy, high hardness material, due to the brittleness of the ceramic matrix, the weak bonding force between fiber and matrix, and the anisotropy of composite material. Burr, delamination, tearing, chips, and other surface damage tend to generate in the machining, resulting in surface quality and strength decline. This paper reviewed the latest abrasive machining technology for SiC ceramic composites. The characteristics and research directions of the main abrasive machining technology, including grinding, laser-assisted grinding, ultrasonic-assisted grinding, and abrasive waterjet machining, are introduced first. Then, the commonly used numerical simulation research for modeling and simulating the machining of ceramic matrix composites is briefly summarized. Finally, the processing difficulties and research hotspots of ceramic matrix composites are summarized.

14.
Clin Interv Aging ; 18: 2009-2019, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38053653

RESUMO

Purpose: The efficacy of mortality risk prediction models among older patients in China remains uncertain. We aimed to validate and compare the performances of the Walter Index, Geriatric Prognostic Index (GPI), Charlson Comorbidity Index (CCI), and FRAIL Scale in predicting 1-year all-cause mortality post-discharge in geriatric inpatients in China. Patients and Methods: This study was conducted at a geriatric ward of a tertiary Hospital in Beijing, including patients aged 70 years or older with a documented comprehensive geriatric assessment, discharged between January 1, 2016, and December 31, 2021. Patients with a hospital stay ≤24 h or >60 days were excluded. All-cause mortality data within one year of discharge were collected from medical files and telephone interviews between August 2022 and February 2023. Multiple imputation, Logistic regression analysis, Brier scores, C-statistics, Hosmer-Lemeshow goodness-of-fit-test, and calibration plots were employed for statistical analysis. Results: We included 832 patients with a median (interquartile range) age of 77 (74-82) years. One-hundred patients (12.0%) died within one year. After adjusting for covariates-marital status, social support, cigarette use, length of stay, number of medications, hemoglobin levels, handgrip strength, and Short Physical Performance Battery-CCI scores of 3-4 and >4, and increased Walter Index, GPI, and FRAIL Scale scores were significantly associated with 1-year mortality risk. The Brier scores varied from 0.07 (Walter Index) to 0.10 (FRAIL Scale). The C-statistic ranged from 0.74 (95% confidence interval, 0.69-0.78) for FRAIL Scale to 0.88 (95% confidence interval, 0.84-0.91) for the Walter Index. Calibration curves showed that the Walter Index, GPI, and FRAIL Scale were well calibrated, while the CCI was poor. Conclusion: Combining the Brier score, discrimination and calibration, the Walter Index was confirmed for the first time to be the best model to predict the 1-year mortality risk of geriatric inpatients in China among the four models.


Assuntos
Assistência ao Convalescente , Força da Mão , Humanos , Idoso , Alta do Paciente , Tempo de Internação , Prognóstico , Avaliação Geriátrica , Idoso Fragilizado
15.
Acad Radiol ; 2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38072725

RESUMO

RATIONALE AND OBJECTIVES: The objective of this study was to develop a comprehensive combined model for predicting occult peritoneal metastasis (OPM) in epithelial ovarian cancers (EOCs) using radiomics features derived from computed tomography (CT) and clinical-radiological predictors. MATERIALS AND METHODS: A total of 224 patients with EOCs were randomly divided into training dataset (N = 156) and test dataset (N = 86). Five clinical factors and seven radiological features were collected. The radiomics features were extracted from CT images of each patient. Multivariate logistic regression was employed to construct clinical and radiological models. The correlation analysis and least absolute shrinkage and selection operator algorithm were used to select radiomics features and build radiomics model. The important clinical, radiological factors, and radiomics features were integrated into a combined model by multivariate logistic regression. Receiver operating characteristics curve with area under the curve (AUC) were used to evaluate and compare predictive performance. RESULTS: Carbohydrate antigen 125 (CA-125) and human epididymal protein 4 (HE-4) were independent clinical predictors. Laterality, thickened septa and margin were independent radiological predictors. In the training dataset, the AUCs for the clinical, radiological and radiomics models in evaluating OPM were 0.759, 0.819, and 0.830, respectively. In the test dataset, the AUCs for these models were 0.846, 0.835, and 0.779, respectively. The combined model outperformed other models in both the training and the test datasets with AUCs of 0.901 and 0.912, respectively. Decision curve analysis indicated that the combined model yielded a higher net benefit compared to the other models. CONCLUSION: The combined model, integrating radiomics features with clinical and radiological predictors exhibited improved accuracy in predicting OPM in EOCs.

16.
Front Bioeng Biotechnol ; 11: 1291824, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026901

RESUMO

Purpose: The combination of near-infrared (NIR) and positron emission tomography (PET) imaging presents an opportunity to utilize the benefits of dual-modality imaging for tumor visualization. Based on the observation that fibroblast activation protein (FAP) is upregulated in cancer-associated fibroblasts (CAFs) infiltrating all solid tumors, including head and neck squamous cell carcinoma (HNSCC), we developed the novel PET/NIR probe [68Ga]Ga-FAP-2286-ICG. Preclinically, the specificity, biodistribution and diagnostic properties were evaluated. Methods: Cell uptake assays were completed with the U87MG cell to evaluate the specificity of the [68Ga]Ga-FAP-2286-ICG. The tumor-targeting efficiency, biodistribution and optimal imaging time window of the [68Ga]Ga-FAP-2286-ICG were studied in mice bearing U87MG xenografts. HNSCC tumor-bearing mice were used to evaluate the feasibility of [68Ga]Ga-FAP-2286-ICG for tumor localization and guided surgical resection of HNSCC tumors. Results: The in vitro experiments confirmed that [68Ga]Ga-FAP-2286-ICG showed good stability, specific targeting of the probe to FAP, and the durable retention effect in high-expressing FAP tumors U87MG cell. Good imaging properties such as good tumor uptake, high tumor-to-background ratios (5.44 ± 0.74) and specificity, and tumor contouring were confirmed in studies with mice bearing the U87MG xenograft. PET/CT imaging of the probe in head and neck cancer-bearing mice demonstrated specific uptake of the probe in the tumor with a clear background. Fluorescence imaging further validated the value of the probe in guiding surgical resection and achieving precise removal of the tumor and residual lesions. Conclusion: In a preclinical model, these attractive [68Ga]Ga-FAP-2286-ICG PET/NIR imaging acquired in head and neck cancer make it a promising FAP-targeted multimodal probe for clinical translation.

17.
Artigo em Inglês | MEDLINE | ID: mdl-37889820

RESUMO

Fusion-based spectral super-resolution aims to yield a high-resolution hyperspectral image (HR-HSI) by integrating the available high-resolution multispectral image (HR-MSI) with the corresponding low-resolution hyperspectral image (LR-HSI). With the prosperity of deep convolutional neural networks, plentiful fusion methods have made breakthroughs in reconstruction performance promotions. Nevertheless, due to inadequate and improper utilization of cross-modality information, the most current state-of-the-art (SOTA) fusion-based methods cannot produce very satisfactory recovery quality and only yield desired results with a small upsampling scale, thus affecting the practical applications. In this article, we propose a novel progressive spatial information-guided deep aggregation convolutional neural network (SIGnet) for enhancing the performance of hyperspectral image (HSI) spectral super-resolution (SSR), which is decorated through several dense residual channel affinity learning (DRCA) blocks cooperating with a spatial-guided propagation (SGP) module as the backbone. Specifically, the DRCA block consists of an encoding part and a decoding part connected by a channel affinity propagation (CAP) module and several cross-layer skip connections. In detail, the CAP module is customized by exploiting the channel affinity matrix to model correlations among channels of the feature maps for aggregating the channel-wise interdependencies of the middle layers, thereby further boosting the reconstruction accuracy. Additionally, to efficiently utilize the two cross-modality information, we developed an innovative SGP module equipped with a simulation of the degradation part and a deformable adaptive fusion part, which is capable of refining the coarse HSI feature maps at pixel-level progressively. Extensive experimental results demonstrate the superiority of our proposed SIGnet over several SOTA fusion-based algorithms.

18.
Skin Res Technol ; 29(10): e13489, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37881051

RESUMO

Poxviruses belong to the Poxviridae family, a group of pathogens known for their high infectivity in humans, posing significant health threats. One of the most well-known representatives of poxvirus infections is smallpox, which has been successfully eradicated. However, in recent years, there has been a resurgence in cases of mpox, another member of the Poxviridae family, raising concerns about the potential for a global pandemic or a worldwide health crisis. While the typical clinical presentation of mpox and other poxvirus infections often involves cutaneous lesions, there have been reports of various atypical and non-classic clinical manifestations. Dermoscopy has emerged as a crucial diagnostic tool, aiding dermatologists in clinical practice to make informed decisions. In this summary, we provide an overview of the clinical and dermoscopic features of representative cutaneous lesions associated with human poxvirus infections, including mpox, orf, milker's nodule, and molluscum contagiosum.


Assuntos
Infecções por Poxviridae , Poxviridae , Humanos , Dermoscopia , Infecções por Poxviridae/diagnóstico por imagem , Infecções por Poxviridae/epidemiologia
19.
Mol Biol Evol ; 40(9)2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37707487

RESUMO

In viral evolution, a new mutation has to proliferate within the host (Stage I) in order to be transmitted and then compete in the host population (Stage II). We now analyze the intrahost single nucleotide variants (iSNVs) in a set of 79 SARS-CoV-2 infected patients with most transmissions tracked. Here, every mutation has two measures: 1) iSNV frequency within each individual host in Stage I; 2) occurrence among individuals ranging from 1 (private), 2-78 (public), to 79 (global) occurrences in Stage II. In Stage I, a small fraction of nonsynonymous iSNVs are sufficiently advantageous to rise to a high frequency, often 100%. However, such iSNVs usually fail to become public mutations. Thus, the selective forces in the two stages of evolution are uncorrelated and, possibly, antagonistic. For that reason, successful mutants, including many variants of concern, have to avoid being eliminated in Stage I when they first emerge. As a result, they may not have the transmission advantage to outcompete the dominant strains and, hence, are rare in the host population. Few of them could manage to slowly accumulate advantageous mutations to compete in Stage II. When they do, they would appear suddenly as in each of the six successive waves of SARS-CoV-2 strains. In conclusion, Stage I evolution, the gate-keeper, may contravene the long-term viral evolution and should be heeded in viral studies.


Assuntos
COVID-19 , Humanos , COVID-19/genética , SARS-CoV-2/genética , Mutação
20.
Int J Mol Sci ; 24(16)2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37628827

RESUMO

The efficient production of silkworm silk is crucial to the silk industry. Silk protein synthesis is regulated by the juvenile hormone (JH) and 20-Hydroxyecdysone (20E). Therefore, the genetic regulation of silk production is a priority. JH binding protein (JHBP) transports JH from the hemolymph to target organs and cells and protects it. In a previous study, we identified 41 genes containing a JHBP domain in the Bombyx mori genome. Only one JHBP gene, BmJHBPd2, is highly expressed in the posterior silk gland (PSG), and its function remains unknown. In the present study, we investigated the expression levels of BmJHBPd2 and the major silk protein genes in the high-silk-producing practical strain 872 (S872) and the low-silk-producing local strain Dazao. We found that BmJHBPd2 was more highly expressed in S872 than in the Dazao strain, which is consistent with the expression pattern of fibroin genes. A subcellular localization assay indicated that BmJHBPd2 is located in the cytoplasm. In vitro hormone induction experiments showed that BmJHBPd2 was upregulated by juvenile hormone analogue (JHA) treatment. BmKr-h1 upregulation was significantly inhibited by the overexpression of BmJHBPd2 (BmJHBPd2OE) at the cell level when induced by JHA. However, overexpression of BmJHBPd2 in the PSG by transgenic methods led to the inhibition of silk fibroin gene expression, resulting in a reduction in silk yield. Further investigation showed that in the transgenic BmJHBPd2OE silkworm, the key transcription factor of the JH signaling pathway, Krüppel homolog 1 (Kr-h1), was inhibited, and 20E signaling pathway genes, such as broad complex (Brc), E74A, and ultraspiracle protein (USP), were upregulated. Our results indicate that BmJHBPd2 plays an important role in the JH signaling pathway and is important for silk protein synthesis. Furthermore, our findings help to elucidate the mechanisms by which JH regulates silk protein synthesis.


Assuntos
Bombyx , Fibroínas , Animais , Bombyx/genética , Seda/genética , Transdução de Sinais , Fibroínas/genética , Transporte Biológico , Animais Geneticamente Modificados
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