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This study aimed to assess the clinical efficacy of umbilical cord mesenchymal stem cells (hUC-MSCs) from different passages (P3, P8, and P13) in the treatment of knee osteoarthritis (OA) and explore the underlying mechanisms. The hUC-MSCs from each passage were characterized and evaluated for their stemness, migration, proliferation, and marker expression. Rats with OA were treated with hUC-MSCs from each passage, and the therapeutic effects were assessed based on knee swelling, discomfort, and pathological examination of the knee joint. Co-culture experiments were conducted to examine the ability of hUC-MSCs to stimulate type II collagen synthesis and inhibit MMP13 expression in chondrocytes. Telomere length and telomerase activity of hUC-MSCs from each passage were measured to investigate the reasons for the observed differences in clinical efficacy. The results revealed that P3 and P8 hUC-MSCs exhibited superior osteogenic and chondrogenic differentiation potential compared to P13, while P13 demonstrated stronger adipogenic differentiation. The wound healing rate was significantly higher in the P3 and P8 groups compared to P13. All hUC-MSC groups expressed high levels of CD90 and CD105, indicating their mesenchymal stem cell characteristics, while CD31 and CD45 were not expressed. CD105 expression was significantly reduced in the P13 group. In the treatment of rat osteoarthritis, there were no significant differences in knee swelling, discomfort, Mankin scores, and pathological findings between P3 and P8 hUC-MSC treatments. However, there was a significant difference between the 8th and 13th passages. Co-culture experiments showed that hUC-MSCs from P3 and P8 enhanced type II collagen synthesis and reduced MMP13 expression in chondrocytes. Although no significant difference was observed between the P3 and P8 groups, a significant difference was found between the P13 and P8 groups. Telomere length analysis revealed that P13 samples had significantly shorter telomeres compared to both P3 and P8. The telomerase activity was positive in P3 and P8 hUC-MSCs, indicating no significant difference between these passages, while it was negative in P13 hUC-MSCs. In conclusion, P3 and P8 hUC-MSCs exhibited superior therapeutic potential for knee osteoarthritis compared to P13, possibly due to their enhanced differentiation capacity and telomerase activity.
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Diferenciação Celular , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Cordão Umbilical , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Animais , Humanos , Cordão Umbilical/citologia , Ratos , Osteoartrite do Joelho/terapia , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/metabolismo , Masculino , Condrócitos/metabolismo , Condrócitos/citologia , Ratos Sprague-Dawley , Osteoartrite/terapia , Osteoartrite/patologia , Osteoartrite/metabolismo , Telomerase/metabolismo , Técnicas de Cocultura , Proliferação de Células , Osteogênese , CondrogêneseRESUMO
Polyamide plays a pivotal role in engineering thermoplastics. Constrained by the harsh conditions and arduous procedures for its industrial synthesis, developing facile synthesis of polyamides is still challengeable and holds profound significance. Herein, we successfully utilized water as one of the monomers to synthesize functional polyamides under ambient conditions. A powerful multicomponent polymerization of water, isocyanides, and chlorooximes was established in phosphate-buffered saline. Soluble and thermally stable polyamides with high weight-average molecular weights (up to 53900) were obtained in excellent yields (up to 95%). The polymerization exhibits unique polymerization-induced emission characteristics, successfully converting non-emissive monomers into unconventional emissive polymers. Notably, the resultant polyamides could undergo effective post-modification via the hydroxyl-yne click reaction. By incorporating various functional groups into the polyamide, its emission color could be fine-tuned from blue to green and to red. Remarkably, the refractive index (n) of the polyamide at 589 nm could be increased from 1.6173 to 1.7227 and the Δn could be unprecedentedly as high as 0.1054 for non-heavy atom-containing polymers after post-modification, and its micron-thick films exhibited excellent transparency in the visible region. Thus, this work not only establishes a powerful polymerization toward novel polyamides but also opens up an avenue for their versatile functionalization.
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Foaming agents as a combination of several components are usually used as soil conditioning during earth pressure balance shield (EPBS) tunnelling. These residues in waste EPBS muck lead to a series of new challenges for in-situ recycling, i.e., foams overflow flocculation tank. This study investigates the effects of residual foaming agent components and defoamers on defoaming-flocculation-filterpress characteristics of EPBS muck using an improved flocculation and filterpress system. Residual foam height (Hf), defoaming ratio (DFR), antifoaming ratio (AFR), total suspended substance (TSS), turbidity, moisture content (MC), and zeta potential (ZP) were selected as characterization indices. The microstructure of filterpress cakes was analyzed using a scanning electron microscope. Results demonstrate that an enhancement within 0.0-1.0wt.% for sodium fatty alcohol polyoxyethylene ether sulfate (AES) and alpha olefin sulfonate (AOS) significantly reduces DFR and AFR. The MC and ZP decline, while the Hf and turbidity enhance. The combinations of nonionic surfactants alkyl polyglycoside (APG) and fatty alcohol-polyoxyethylene ether (AEO) in a concentration range of 0.0-1.0wt.% with 0.2wt.% AES causes the Hf, DFR, AFR, turbidity, and ZP to exhibit absolutely different variations. The MC with the growth in both APG and AEO presents a trend of first decreasing and then increasing. By increasing foam stabilizers sodium carboxymethyl cellulose (CMC) and guar gum (GG) within 0.02-0.10wt.%, the AFR, TSS, and ZP enhance in varying degrees, while the Hf, DFR, and MC gradually reduce. With the increase of defoamers hydroxyl silicone oil-glycerol polyoxypropylene ether (H-G) and dimethyl silicone oil-glycerol polyoxypropylene ether (D-G) within 0.002-0.010wt.%, the DFR and AFR are significantly improved, while the TSS, turbidity, MC, and ZP display varying degrees of reduction. Moreover, defoaming-flocculation-filterpress mechanisms of EPBS muck are explored to provide a useful reference for actual in-situ recycling projects.
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Floculação , Pressão , Solo/química , Tensoativos/químicaRESUMO
The µTAS/LOC, a highly integrated microsystem, consolidates multiple bioanalytical functions within a single chip, enhancing efficiency and precision in bioanalysis and biomedical operations. Microfluidic centrifugation, a key component of LOC devices, enables rapid capture and enrichment of tiny objects in samples, improving sensitivity and accuracy of detection and diagnosis. However, microfluidic systems face challenges due to viscosity dominance and difficulty in vortex formation. Acoustic-based centrifugation, particularly those using surface acoustic waves (SAWs), have shown promise in applications such as particle concentration, separation, and droplet mixing. However, challenges include accurate droplet placement, energy loss from off-axis positioning, and limited energy transfer from low-frequency SAW resonators, restricting centrifugal speed and sample volume. In this work, we introduce a novel ring array composed of eight Lamb wave resonators (LWRs), forming an Ultra-Fast Centrifuge Tunnel (UFCT) in a microfluidic system. The UFCT eliminates secondary vortices, concentrating energy in the main vortex and maximizing acoustic-to-streaming energy conversion. It enables ultra-fast centrifugation with a larger liquid capacity (50 µL), reduced power usage (50 mW) that is one order of magnitude smaller than existing devices, and greater linear speed (62 mm/s), surpassing the limitations of prior methods. We demonstrate successful high-fold enrichment of 2 µm and 10 µm particles and explore the UFCT's potential in tissue engineering by encapsulating cells in a hydrogel-based micro-organ with a ring structure, which is of great significance for building more complex manipulation platforms for particles and cells in a bio-compatible and contactless manner.
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Centrifugação , Humanos , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas , AcústicaRESUMO
Particles, ranging from submicron to nanometer scale, can be broadly categorized into biological and non-biological types. Submicron-to-nanoscale bioparticles include various bacteria, viruses, liposomes, and exosomes. Non-biological particles cover various inorganic, metallic, and carbon-based particles. The effective manipulation of these submicron to nanoparticles, including their separation, sorting, enrichment, assembly, trapping, and transport, is a fundamental requirement for different applications. Acoustofluidics, owing to their distinct advantages, have emerged as a potent tool for nanoparticle manipulation over the past decade. Although recent literature reviews have encapsulated the evolution of acoustofluidic technology, there is a paucity of reports specifically addressing the acoustical manipulation of submicron to nanoparticles. This article endeavors to provide a comprehensive study of this topic, delving into the principles, apparatus, and merits of acoustofluidic manipulation of submicron to nanoparticles, and discussing the state-of-the-art developments in this technology. The discourse commences with an introduction to the fundamental theory of acoustofluidic control and the forces involved in nanoparticle manipulation. Subsequently, the working mechanism of acoustofluidic manipulation of submicron to nanoparticles is dissected into two parts, dominated by the acoustic wave field and the acoustic streaming field. A critical analysis of the advantages and limitations of different acoustofluidic platforms in nanoparticles control is presented. The article concludes with a summary of the challenges acoustofluidics face in the realm of nanoparticle manipulation and analysis, and a forecast of future development prospects.
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Toxocara canis is a parasitic zoonose that is distributed worldwide and is one of the two pathogens causing toxocariasis. After infection, it causes serious public health and safety problems, which pose significant veterinary and medical challenges. To better understand the regulatory effects of T. canis infection on the host immune cells, murine macrophages (RAW264.7) were incubated with recombinant T. canis C-type lectin 4 (rTc-CTL-4) protein in vitro. The quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to analyze the nucleotide-binding oligomerization domain-containing protein 1/2 (NOD1/2), receptor-interacting protein 2 (RIP2), nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), and mitogen-activated protein kinase (MAPK) on mRNA level and protein expression level in macrophages. Our results indicated that 10 µg/mL rTc-CTL-4 protein could modulate the expression of NOD1, NOD2, and RIP2 at both the transcriptional and translational levels. The protein translation levels of NF-κB, P-p65, p38, and P-p38 in macrophages were also modulated by rTc-CTL-4 protein. Macrophages were co-incubated with rTc-CTL-4 protein after siRNA silencing of NOD1, NOD2, and RIP2. The expression levels of NF-κB, P-p65, p38, and P-p38 were significantly changed compared with the negative control groups (Neg. Ctrl.). Taken together, rTc-CTL-4 protein seemed to act on NOD1/2-RIP2-NF-κB and MAPK signaling pathways in macrophages and might activate MAPK and NF-κB signaling pathways by regulating NOD1, NOD2, and RIP2. The insights from the above studies could contribute to our understanding of immune recognition and regulatory mechanisms of T. canis infection in the host animals.
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NF-kappa B , Toxocara canis , Animais , Camundongos , NF-kappa B/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Toxocara canis/metabolismo , Transdução de Sinais/fisiologia , MacrófagosRESUMO
Undifferentiated pleomorphic sarcoma (UPS) is a highly aggressive malignant soft tissue tumor with a poor prognosis; however, the identity and heterogeneity of tumor populations remain elusive. Here, eight major cell clusters were identified through the RNA sequencing of 79,569 individual cells of UPS. UPS originates from mesenchymal stem cells (MSCs) and features undifferentiated subclusters. UPS subclusters were predicted to exist in two bulk RNA datasets, and had a prognostic value in The Cancer Genome Atlas (TCGA) dataset. The functional heterogeneity of malignant UPS cells and the immune microenvironment were characterized. Additionally, the fused cells were innovatively detected by expressing both monocyte/macrophage markers and other subcluster-associated genes. Based on the ligand-receptor interaction analysis, cellular interactions with epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) were abundant. Furthermore, 73% of patients with UPS (48/66) showed positive EGFR expression, which was associated with a poor prognosis. EGFR blockade with cetuximab inhibited tumor growth in a patient-derived xenograft model. Our transcriptomic studies delineate the landscape of UPS intratumor heterogeneity and serve as a foundational resource for further discovery and therapeutic exploration.
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Receptores ErbB , Sarcoma , Análise de Célula Única , Humanos , Animais , Receptores ErbB/genética , Receptores ErbB/metabolismo , Camundongos , Sarcoma/patologia , Sarcoma/genética , Prognóstico , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto , Cetuximab/farmacologia , Cetuximab/uso terapêutico , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão GênicaRESUMO
The rapid growth of artificial intelligence is revolutionizing classical engineering society, offering novel approaches to material and structural design and analysis. Among various scientific machine learning techniques, physics-informed neural network (PINN) has been one of the most researched subjects, for its ability to incorporate physics prior knowledge into model training. However, the intrinsic continuity requirement of PINN demands the adoption of domain decomposition when multiple materials with distinct properties exist. This greatly complicates the gradient computation of design features, restricting the application of PINN to structural shape optimization. To address this, we present a novel framework that employs neural network coordinate projection for shape optimization within PINN. This technique allows for direct mapping from a standard shape to its optimal counterpart, optimizing the design objective without the need for traditional transition functions or the definition of intermediate material properties. Our method demonstrates a high degree of adaptability, allowing the incorporation of diverse constraints and objectives directly as training penalties. The proposed approach is tested on magnetostatic problems for iron core shape optimization, a scenario typically plagued by the high permeability contrast between materials. Validation with finite-element analysis confirms the accuracy and efficiency of our approach. The results highlight the framework's capability as a viable tool for shape optimization in complex material design tasks.
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Synthetic aperture Ladar (SAL) is an extension of synthetic aperture technology in the optical frequency band. Owing to the short wavelength of lasers, the system has high-resolution, high-data-rate, and refined imaging capabilities, which has potential in high-resolution observation fields such as ground observation and space target observation. However, the short wavelength of lasers also makes SAL severely sensitive to vibrations even on the micron order which cause azimuth defocusing and range cell migration. To address this problem, we establish a de-chirp signal model under vibration environment, and propose a vibration error estimation and compensation method using triangular interferometric signals. According to the symmetrical characteristics of triangular frequency modulated continuous wave (T-FMCW) and the time-frequency information introduced by the azimuthal vibration phase, we use a two-stage interferometry method to estimate instantaneous frequency introduced by the vibration errors that cause range cell migration. For the scenarios without obvious range cell migration, we use a one-stage interferometry method to estimate the instantaneous frequency. Subsequently, we establish a vibration compensation filter using the estimated instantaneous frequency to compensate for the vibration errors. We use two experiments to verify the effectiveness and superiority of the proposed method. The results show that the proposed method effectively eliminates range cell migration and azimuthal phase errors introduced by vibration errors, producing SAL imaging results with higher resolution than the conventional spectral correlation method.
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Earth pressure balance (EPB) shield is increasingly employed in metro tunnel construction, and causes a series of environmental, safety, and resource waste problems due to the disposal of a considerable amount of muck. In situ recycling of EPB shield muck is an effective solution, whereas the foam is generated by residual foaming agents used as the muck conditioning material during tunnelling, which often adsorbs clay particles and overflows the flocculation tank. To achieve defoaming and antifoaming during the reuse of muck, this study prepared novel eco-friendly silicone oil-polyether defoamers by condensation, compounding, and shear emulsification. Defoaming and antifoaming performances of different defoamers were tested using a modified Ross-Miles method and a scale model of field flocculation systems. The results indicated that a high efficiency in defoam and antifoam was characterized by chemical grafting of nano-SiO2 from silicone oils, uniform distribution and large size of grains, low viscosity, and surface tension. The defoamer dosage of 0.002-0.004 wt% near critical micelle concentration (CMC) for each defoamer is reasonable. Overall, the prepared hydroxyl silicone oil-glycerol polyoxypropylene ether (H-G) defoamer compared with other silicone oil-polyether defoamers and commercial defoamers presents the highest defoaming and antifoaming efficiency. Considering the effects of EPB shield muck, the H-G defoamer is least affected by the compound materials and increasing concentration of the commercial foaming agent. Nevertheless, the stability of the H-G emulsion system is weaker than that of the dimethyl silicone oil-glycerol polyoxypropylene ether (D-G) emulsion system after 1 month of sealed storage.
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Antiespumantes , Polímeros , Propilenoglicóis , Óleos de Silicone , Antiespumantes/química , Antiespumantes/farmacologia , Óleos de Silicone/química , Emulsões/química , Glicerol , Tensoativos , ÉteresRESUMO
BACKGROUND: Visceral sarcoma is a rare malignancy with a poor prognosis. However, there is no recommended prognostic staging system for the malignant disease. METHOD: We analyzed the data of patients diagnosed with primary soft tissue sarcoma (STS) of the abdomen and thoracic visceral organs between 2006 and 2017 at our hospital. Prognostic factors (size, tumor grade, and lymph node metastasis) were analyzed in our cohort (n = 203) and the SEER validation cohort (n = 5826). RESULTS: Tumor size, grade, and lymph node metastasis were important prognostic factors for visceral sarcoma in both our and the SEER cohorts. Based on these prognostic factors, we established a new staging system for visceral sarcoma, by which patients could be stratified into clinically meaningful and non-overlapping stages in both our cohort and the SEER validation series. Moreover, the area under the curve (AUC) value of the staging system for 5-year survival was 0.84 (95% CI: 0.78-0.89) in our series and 0.80 (95% CI: 0.79-0.81) in SEER series, respectively. In addition, compared with the widely used FIGO staging system for female genital sarcoma, the visceral sarcoma staging system could more effectively and reliably stratify patients into four different prognostic groups. CONCLUSIONS: The visceral sarcoma staging system is applicable for STS of the abdomen and thoracic visceral organs and is better than the current FIGO staging system for female genital sarcoma and should be incorporated into the AJCC Cancer Staging Manual.
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Estadiamento de Neoplasias , Programa de SEER , Sarcoma , Humanos , Feminino , Sarcoma/patologia , Sarcoma/mortalidade , Masculino , Pessoa de Meia-Idade , Idoso , Prognóstico , Adulto , Metástase Linfática , Gradação de Tumores , Adulto Jovem , Adolescente , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Neoplasias Abdominais/patologia , Neoplasias Abdominais/mortalidadeRESUMO
Ferroptosis is associated with the occurrence and development of many diseases, which is the result of an imbalance in cellular metabolism and oxidation-reduction balance. Therefore, it is an effective therapeutic strategy that simultaneously regulating the intracellular oxidation-reduction system. Herein, a click reaction of alkynylamide with thiol groups in the presence of amine or in PBS (pH = 7.4) is developed, which can react efficiently with thiol substances, such as cysteine (Cys), glutathione (GSH), and bovine serum albumin (BSA). Notably, MBTB-PA, an aggregation-induced emission (AIE) photosensitizer with an alkynylamide unit, is synthesized and its intracellular behavior is visualized in situ by fluorescence imaging, demonstrating its excellent ability to target the endoplasmic reticulum. Furthermore, MBTB-PA reacted with proteins in tumor cells, consumed reducing substances, and triggered intracellular oxidative stress, resulting in cell death. Based on this reaction therapy strategy, click reaction is combined with photodynamic therapy to achieve effective killing of tumor cells by simultaneously raising the intracellular oxidative state and reducing the reductive state. This work not only develops an application of click reaction of alkynamide with thiol in bioconjugation and anti-tumor therapy, but also provides feasible ideas for organic reactions in the exploration of organisms.
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Química Click , Compostos de Sulfidrila , Compostos de Sulfidrila/química , Humanos , Linhagem Celular Tumoral , Animais , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêuticoRESUMO
Mononuclear nonheme iron(II) and 2-oxoglutarate (Fe/2OG)-dependent oxygenases and halogenases are known to catalyze a diverse set of oxidative reactions, including hydroxylation, halogenation, epoxidation, and desaturation in primary metabolism and natural product maturation. However, their use in abiotic transformations has mainly been limited to C-H oxidation. Herein, we show that various enzymes of this family, when reconstituted with Fe(II) or Fe(III), can catalyze Mukaiyama hydration-a redox neutral transformation. Distinct from the native reactions of the Fe/2OG enzymes, wherein oxygen atom transfer (OAT) catalyzed by an iron-oxo species is involved, this nonnative transformation proceeds through a hydrogen atom transfer (HAT) pathway in a 2OG-independent manner. Additionally, in contrast to conventional inorganic catalysts, wherein a dinuclear iron species is responsible for HAT, the Fe/2OG enzymes exploit a mononuclear iron center to support this reaction. Collectively, our work demonstrates that Fe/2OG enzymes have utility in catalysis beyond the current scope of catalytic oxidation.
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Ferro , Oxigenases , Oxigenases/metabolismo , Ferro/metabolismo , Ácidos Cetoglutáricos/metabolismo , Oxirredução , Catálise , HidrogênioRESUMO
Optical aberrations of optical systems cause significant degradation of imaging quality. Aberration correction by sophisticated lens designs and special glass materials generally incurs high cost of manufacturing and the increase in the weight of optical systems, thus recent work has shifted to aberration correction with deep learning-based post-processing. Though real-world optical aberrations vary in degree, existing methods cannot eliminate variable-degree aberrations well, especially for the severe degrees of degradation. Also, previous methods use a single feed-forward neural network and suffer from information loss in the output. To address the issues, we propose a novel aberration correction method with an invertible architecture by leveraging its information-lossless property. Within the architecture, we develop conditional invertible blocks to allow the processing of aberrations with variable degrees. Our method is evaluated on both a synthetic dataset from physics-based imaging simulation and a real captured dataset. Quantitative and qualitative experimental results demonstrate that our method outperforms compared methods in correcting variable-degree optical aberrations.
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BACKGROUND: Fine-needle aspiration (FNA) cytology is a rapid, inexpensive, and uncomplicated method. However, its role in the assessment of soft tissue lesions (STL) remains controversial, and its ability to guide surgical treatment remains unclear. This study investigated the positive predictive value (PPV) of FNA for detecting malignancy and its guiding role in the surgical treatment of STL. METHODS: We retrospectively reviewed 514 patients with STL who underwent preoperative FNA and surgical resection between March 2015 and August 2021. Imaging assessments confirmed that radical surgery was possible. The FNA results were compared with the final postoperative histopathology. RESULTS: Of the 514 patients with STL, 496 (mean age, 48.9 years; range, 21-91 years) were eligible for analysis, the male to female ratio was 111:100. According to the 496 FNA results, 90 (18.2%) were positive for malignancy, 84 (16.9%) were suspicious for malignancy, 80 (16.1%) were spindle cell present, and 242 (48.8%) were negative for malignant cells. Compared with postoperative histopathology, FNA correctly detected all 90 malignant lesions and 203 of the 242 benign lesions. A total of 39 false-negative results were obtained. FNA showed an accuracy of 88.3%, sensitivity of 69.8%, specificity of 100%, negative predictive value (NPV) of 83.9%, and PPV of 100%. In the other seven validation cohorts (n = 1157), FNA had a consistently high PPV, with values all more than 93%. CONCLUSION: Our results demonstrate that FNA has a high PPV for detecting malignancy. For patients with resectable lesions and malignant FNA, the core needle biopsy (CNB) step can be omitted with multidisciplinary evaluation, and subsequent radical surgery can be performed.
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Neoplasias , Adulto , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Biópsia por Agulha Fina/métodos , Estudos Retrospectivos , Sensibilidade e Especificidade , China , Biópsia com Agulha de Grande CalibreRESUMO
The research on pharmacology usually focuses on the structure-activity relationships of drugs, such as antibiotics, to enhance their activity, but often ignores their optical properties. However, investigating the photophysical properties of drugs is of great significance because they could be used to in situ visualize their positions and help us to understand their working metabolism. In this work, we identified a class of commercialized antibiotics, such as levofloxacin, norfloxacin, and moxifloxacin (MXF) hydrochloride, featuring the unique aggregation-induced emission (AIE) characteristics. By taking advantage of their AIE feature, antibiotic metabolism in cells could be in situ visualized, which clearly shows that the luminescent aggregates accumulate in the lysosomes. Moreover, after a structure-activity relationship study, we found an ideal site of MXF to be modified with a triphenylphosphonium and an antibiotic derivative MXF-P was prepared, which is able to specifically differentiate bacterial species after only 10 min of treatment. Moreover, MXF-P shows highly effective broad-spectrum antibacterial activity, excellent therapeutic effects and biosafety for S. aureus-infected wound recovery. Thus, this work not only discovers the multifunctionalities of the antibiotics but also provides a feasible strategy to make the commercialized drugs more powerful.
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It is well-known that bacterial infections will induce a variety of diseases in the clinic. In particular, the emergence of drug-resistant bacteria has increased the threat to human health. The development of multiple modes of therapy will effectively fight against drug-resistant bacterial infections. In this work, we covalently attached an AIE photosensitizer to the antibiotic of moxifloxacin hydrochloride (MXF-HCl) and synthesized an antibiotic derivative, MXF-R, with pharmacological activity and photodynamic activation. In infected cells, MXF-R showed enhanced fluorescence after it specifically binds to bacteria; thus, in situ visualization of the bacteria was realized. Notably, through chemo- and photodynamic therapy, MXF-R exhibited better antibacterial activity than its parent antibiotic in rapid sterilization, and it achieved effective killing for moxifloxacin resistant bacteria. In addition, MXF-R shows a broad-spectrum antibacterial effect and could be used in the recovery therapy of infected wounds in mice, demonstrative of a significant therapeutic effect and good biological safety. Thus, as a promising multifunctional antibacterial agent, MXF-R will have tremendous potential in in situ visualization study and killing of drug-resistant bacteria. This work provides an innovative strategy for solving critical disease through the combination of materials and biomedical sciences.
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Oral infectious diseases and tooth staining, the main challenges of dental healthcare, are inextricably linked to microbial colonization and the formation of pathogenic biofilms. However, dentistry has so far still lacked simple, safe, and universal prophylactic options and therapy. Here, we report copper-doped carbon dots (Cu-CDs) that display enhanced catalytic (catalase-like, peroxidase-like) activity in the oral environment for inhibiting initial bacteria (Streptococcus mutans) adhesion and for subsequent biofilm eradication without impacting the surrounding oral tissues via oxygen (O2) and reactive oxygen species (ROS) generation. Especially, Cu-CDs exhibit strong affinity for lipopolysaccharides (LPS) and peptidoglycans (PGN), thus conferring them with excellent antibacterial ability against Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli), such that they can prevent wound purulent infection and promoting rapid wound healing. Additionally, the Cu-CDs/H2O2 system shows a better performance in tooth whitening, compared with results obtained with other alternatives, e.g., CDs and clinically used H2O2, particularly its negligible enamel and dentin destruction. It is anticipated that the biocompatible Cu-CDs presented in this work are a promising nano-mouthwash for eliminating oral pathogenic biofilms, prompting wound healing as well as tooth whitening, highlighting their significance in oral health management.
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Cobre , Infecção dos Ferimentos , Humanos , Cobre/farmacologia , Carbono , Peróxido de Hidrogênio , Staphylococcus aureus , Biofilmes , Antibacterianos/farmacologia , Escherichia coli , Coloração e RotulagemRESUMO
Photodynamic therapy as an emerging phototheranostic approach holds great potential for antibacterial treatment, but is limited by compromised reactive oxygen species (ROS) generation in an aggregate and hypoxic microenvironment. Herein, we report a molecular cationization approach to boost the ROS, especially type I ROS generation of aggregation-induced emission (AIE) photosensitizers for photodynamic treatment of drug-resistant bacteria. Such cationization reinforces the electron-accepting ability of the cationic moiety, promotes intersystem crossing (ISC), and increases electron separation and transfer processes. The resultant CTBZPyI exhibits largely enhanced ROS generation ability with predominant hydroxyl radical generation over its neutral counterpart in aggregate. Moreover, cationization also confers CTBZPyI with the bacterial binding ability and a moderate bacterial inactivation ability in the dark. Further light irradiation leads to superb antibacterial performance, which largely promotes the healing process of a MRSA-infected wound. Such a cationization strategy is expected to be a general strategy for the design of highly effective type I photosensitizers for bacterial infection treatment.
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Fotoquimioterapia , Fármacos Fotossensibilizantes , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Antibacterianos/farmacologia , Bactérias/metabolismoRESUMO
Circular synthetic aperture radar (CSAR), which can observe the region of interest for a long time and from multiple angles, offers the opportunity for moving-target detection (MTD). However, traditional MTD methods cannot effectively solve the problem of high probability of false alarm (PFA) caused by strong clutter. To mitigate this, a novel, three-step scheme combining clutter background extraction, multichannel clutter suppression, and the degree of linear consistency of radial velocity interferometric phase (DLRVP) test is proposed. In the first step, the spatial similarity of the scatterers and the correlation between sub-aperture images are fused to extract the strong clutter mask prior to clutter suppression. In the second step, using the data remaining after elimination of the background clutter in Step 1, an amplitude-based detector with higher processing gain is utilized to detect potential moving targets. In the third step, a novel test model based on DLRVP is proposed to further reduce the PFA caused by isolated strong scatterers. After the above processing, almost all false alarms are excluded. Measured data verified that the PFA of the proposed method is only 20% that of the comparison method, with improved detection of slow and weakly moving targets and with better robustness.