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Type I interferon (IFN) is critical for controlling pathogen infection; however, its regulatory mechanisms in plasmacytoid cells (pDCs) still remain unclear. Here, we have shown that nucleic acid sensors cGAS-, STING-, MDA5-, MAVS-, or transcription factor IRF3-deficient mice produced high amounts of type I IFN-α and IFN-ß (IFN-α/ß) in the serum and were resistant to lethal plasmodium yoelii YM infection. Robust IFN-α/ß production was abolished when gene encoding nucleic acid sensor TLR7, signaling adaptor MyD88, or transcription factor IRF7 was ablated or pDCs were depleted. Further, we identified SOCS1 as a key negative regulator to inhibit MyD88-dependent type I IFN signaling in pDCs. Finally, we have demonstrated that pDCs, cDCs, and macrophages were required for generating IFN-α/ß-induced subsequent protective immunity. Thus, our findings have identified a critical regulatory mechanism of type I IFN signaling in pDCs and stage-specific function of immune cells in generating potent immunity against lethal YM infection.
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Imunidade Adaptativa/imunologia , Células Dendríticas/imunologia , Interferon Tipo I/imunologia , Malária/imunologia , Transdução de Sinais/imunologia , Animais , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Técnicas de Silenciamento de Genes , Camundongos , Camundongos Knockout , Plasmodium yoelii , Reação em Cadeia da PolimeraseRESUMO
Oversampled modulation (OM) and undersampled modulation (UM) are two commonly used optical camera communication (OCC) modulation schemes for high-speed communication in short-range and reliable communication at long distances, respectively. However, the relationship between these two schemes and the tradeoff in performance for arbitrary communication distances have not been thoroughly investigated. In this study, we analyze the impact of distance and modulation parameters on pixel efficiency and packet delivery rate performance, demonstrating the underlying unity of traditional OM and UM schemes. Furthermore, we propose a generalized modulation scheme that allows for achieving predefined link performance at a given distance by adjusting the modulation parameters, such as packet length and repetition counts. Simulation and experimental results show that the proposed generalized modulation scheme provides OCC with a unique distance-aware capability other than the traditional OM and UM schemes, which are two special cases focusing on effectiveness and reliability, respectively. This research enhances our understanding of OCC data modulation and establishes a theoretical foundation for achieving efficient and reliable OCC transmission in complex environments.
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Integration of multi-dimensional optical information enhances the recognition and anti-interference capabilities of the detection system, allowing for better adaptation to complex environments. Therefore, this technology represents a crucial developmental pathway for the future of infrared optical detectors. In this study, a dual-band polarization photodetector based on a two-dimensional α-MoO3 grating structure is proposed. The structure utilizes the special dispersion property of the α-MoO3 material to excite the localized plasmon resonance, which generates narrowband high absorption peaks with Q-factors as high as 110.24 and 92.65, with peaks close to 1 under TM and TE polarized waves, respectively. The direct measurement of multi-dimensional optical information including intensity, spectrum and polarization states is realized. By adjusting the structural parameters, polarization-dependent dual-band detection can be achieved. Meanwhile, the introduction of graphene material realizes the electronically tunable function of the device. This study provides unexplored strategies for realizing more efficient, flexible and versatile dual-band polarization wave detection.
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Energy metabolism is essential for insect development, reproduction and detoxification. Insects often reallocate energy and resources to manage external stress, balancing the demands of detoxification and reproduction. Glucose transport 4 (Glut4), a glucose transporter, is involved in glucose and lipid metabolism. However, the specific molecular mechanism of Glut4 in insect reproduction, and its role in the response to insecticide-induced oxidative stress remain unclear. In this study, LmGlut4 was identified and analyzed in Locusta migratoria. Silencing of LmGlut4 significantly reduced vitellogenin (Vg) biosynthesis in the fat body and Vg absorption by oocytes, ultimately hindering ovarian development and oocyte maturation. Knockdown of LmGlut4 also inhibited the biosynthesis of key insect hormones, such as juvenile hormone (JH), 20-hydroxyecdysone (20E) and insulin. Furthermore, LmGlut4 knockdown led to reduced triglyceride (TG) and glycogen content in the fat body and ovary, as well as decreased capacity for trehalose biosynthesis in adipocytes. Additionally, dsLmGlut4-treated locusts showed heightened sensitivity to deltamethrin, leading to increased triglyceride depletion during detoxification. This study sheds light on the biological function of LmGlut4 in the ovary and provides potential target genes for exploring biological pest management strategies.
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Transportador de Glucose Tipo 4 , Inseticidas , Locusta migratoria , Nitrilas , Ovário , Piretrinas , Interferência de RNA , Animais , Piretrinas/farmacologia , Feminino , Nitrilas/farmacologia , Ovário/metabolismo , Ovário/efeitos dos fármacos , Transportador de Glucose Tipo 4/metabolismo , Transportador de Glucose Tipo 4/genética , Locusta migratoria/genética , Locusta migratoria/efeitos dos fármacos , Locusta migratoria/metabolismo , Inseticidas/farmacologia , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Vitelogeninas/metabolismo , Vitelogeninas/genética , Metabolismo Energético/efeitos dos fármacos , Corpo Adiposo/metabolismo , Corpo Adiposo/efeitos dos fármacos , Hormônios Juvenis/metabolismo , Hormônios Juvenis/farmacologia , Oócitos/metabolismo , Oócitos/efeitos dos fármacos , Triglicerídeos/metabolismoRESUMO
BACKGROUND: Cymbidium sinense is an orchid that is typically used as a potted plant, given its high-grade ornamental characteristics, and is most frequently distributed in China and SE Asia. The inability to strictly regulate flowering in this economically important potted and cut-flower orchid is a bottleneck that limits its industrial development. Studies on C. sinense flowering time genes would help to elucidate the mechanism regulating flowering. There are very few studies on the genetic regulation of flowering pathways in C. sinense. Photoperiod significantly affects the flowering of C. sinense, but it was unknown how the CONSTANS gene family is involved in regulating flowering. RESULTS: In this study, eight CONSTANS-like genes were identified and cloned. They were divided into three groups based on a phylogenetic analysis. Five representative CsCOL genes (CsCOL3/4/6/8/9) were selected from the three groups to perform expression characterization and functional study. CsCOL3/4/6/8/9 are nucleus-localized proteins, and all five CsCOL genes were expressed in all organs, mainly in leaves followed by sepals. The expression levels of CsCOL3/4 (group I) were higher in all organs than other CsCOL genes. Developmental stage specific expression revealed that the expression of CsCOL3/4/9 peaked at the initial flowering stage. In contrast, the transcript level of CsCOL6/8 was highest at the pedicel development stage. Photoperiodic experiments demonstrated that the transcripts of the five CsCOL genes exhibited distinct diurnal rhythms. Under LD conditions, the overexpression of CsCOL3/4 promoted early flowering, and CsCOL6 had little effect on flowering time, whereas CsCOL8 delayed flowering of Arabidopsis thaliana. However, under SD conditions, overexpression of CsCOL4/6/8 promoted early flowering and the rosette leaves growth, and CsCOL3 induced flower bud formation in transgenic Arabidopsis. CONCLUSION: The phylogenetic analysis, temporal and spatial expression patterns, photoperiodic rhythms and functional study indicate that CsCOL family members in C. sinense were involved in growth, development and flowering regulation through different photoperiodic pathway. The results will be useful for future research on mechanisms pertaining to photoperiod-dependent flowering, and will also facilitate genetic engineering-based research that uses Cymbidium flowering time genes.
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Proteínas de Arabidopsis , Arabidopsis , Filogenia , Fotoperíodo , Ritmo Circadiano , Proteínas de Arabidopsis/genética , Arabidopsis/metabolismo , Flores , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/metabolismoRESUMO
OBJECTIVE: To evaluate the diagnostic performance and cost-effectiveness of calcitonin assays in fine-needle aspiration washout fluid (FNA-CT) compared to fine-needle aspiration cytology (FNAC) for medullary thyroid carcinoma (MTC). METHODS: A total of 27,404 patients from three medical centres between January 2020 and May 2022 were screened for serum calcitonin (sCT). Of whom, 223 patients met endpoints and were enroled for analyses. Based on sCT levels, patients were divided into two groups (group 1: 10 pg/ml< sCT ≤100 pg/ml and group 2: sCT > 100 pg/ml). The diagnostic performance and cost-effectiveness of FNA-CT and FNAC were compared. RESULTS: Most patients (N = 25,228; 92.1%) with thyroid nodules had normal sCT levels. In group 1, 24 and 167 nodules were diagnosed as MTC and non-MTC lesions, respectively. FNA-CT showed better performance in diagnosing MTC than FNAC in terms of sensitivity (100.0% vs. 58.3%), negative predictive value (100.0% vs. 94.3%), and overall accuracy (100.0% vs. 94.7%). In group 2, 67 and 7 nodules were diagnosed as MTC and non-MTC lesions, respectively. The diagnostic performance of FNA-CT was superior to FNAC in terms of sensitivity (100.0% vs. 64.2%), negative predictive value (100.0% vs. 22.6%), and overall accuracy (100.0% vs. 67.6%). Furthermore, analysis from the decision tree model showed that FNA-CT was a cost-effective tool for diagnosing MTC lesions. CONCLUSIONS: FNA-CT can serve as an auxiliary and cost-effective approach for patients with indeterminate sCT levels to detect occult MTC lesions. FNA-CT can be recommended for patients with sCT >100 pg/ml to overcome the high false-negative rate of FNAC.
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Conservadores da Densidade Óssea , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Calcitonina/análise , Análise Custo-Benefício , Biópsia por Agulha Fina , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Hormônios e Agentes Reguladores de Cálcio , Tomografia Computadorizada por Raios XRESUMO
Long noncoding RNAs (lncRNAs) are regulatory RNAs involved in numerous biological processes. Many plant lncRNAs have been identified, but their regulatory mechanisms remain largely unknown. A resource that enables the investigation of lncRNA activity under various conditions is required because the co-expression between lncRNAs and protein-coding genes may reveal the effects of lncRNAs. This study developed JustRNA, an expression profiling resource for plant lncRNAs. The platform currently contains 1 088 565 lncRNA annotations for 80 plant species. In addition, it includes 3692 RNA-seq samples derived from 825 conditions in six model plants. Functional network reconstruction provides insight into the regulatory roles of lncRNAs. Genomic association analysis and microRNA target prediction can be employed to depict potential interactions with nearby genes and microRNAs, respectively. Subsequent co-expression analysis can be employed to strengthen confidence in the interactions among genes. Chromatin immunoprecipitation sequencing data of transcription factors and histone modifications were integrated into the JustRNA platform to identify the transcriptional regulation of lncRNAs in several plant species. The JustRNA platform provides researchers with valuable insight into the regulatory mechanisms of plant lncRNAs. JustRNA is a free platform that can be accessed at http://JustRNA.itps.ncku.edu.tw.
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MicroRNAs , RNA Longo não Codificante , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação da Expressão Gênica , Fatores de Transcrição/metabolismo , Perfilação da Expressão Gênica , RNA de Plantas/genéticaRESUMO
The exposure effect of cameras in optical camera communication (OCC) distorts the received light pulses and generates inter-symbol interference (ISI), which adversely affects the bit error rate (BER) performance. In this Letter, we derive an analytical expression of BER based on the pulse response model of the camera-based OCC channel and analyze the impact of exposure time on BER performance considering asynchronous transmission characteristics. Numerical simulations and experimental results demonstrate that a long exposure time is beneficial in a noise-dominant communication scenario, while a short exposure time is preferable when ISI is dominant. This Letter provides a comprehensive analysis of the influence of exposure time on BER performance, offering a theoretical foundation for the design and optimization of OCC systems.
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Dispositivos ÓpticosRESUMO
This study aims to assess urate-lowering therapy adherence and the relationship with medication beliefs, self-efficacy, depression, anxiety, and COVID-19 pandemic-related concerns in Chinese gout patients during the COVID-19 outbreak. 101 gout patients receiving urate-lowering therapy were involved to evaluate adherence, medication beliefs, self-efficacy, depression, anxiety, and COVID-19 pandemic-related concerns via a mobile app-based questionnaire. Statistical analysis was performed using SPSS 22.0. A total of 101 valid responses were included in the statistical analysis. The results showed that, the rate of adherence to urate-lowering therapy during the COVID-19 outbreak was 22.8% in Chinese patients with gout, higher than that in normal times (9.6%). Compared to the adherent group, non-adherent gout patients had shorter disease duration, lower self-efficacy, lower necessity about urate-lowering therapy score, higher concerns about urate-lowering therapy score, and smaller necessity-concerns differential. Depression and anxiety rates (3.0% and 5.0%, respectively) during the COVID-19 break were lower than that in normal times. Additionally, depression, anxiety, as well as COVID-19 pandemic-related concerns (27.7%) were not related to urate-lowering therapy adherence. In conclusion, adherence rate to urate-lowering therapy in Chinese gout patients during the COVID-19 outbreak was 22.8%, higher than normal times, but still very poor. Except for a little concern about being more susceptible to the virus, patients' mental state is relatively good. While the country puts great efforts into COVID-19 prevention and control, attention must also be paid to the medication management of patients with chronic diseases such as gout.
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COVID-19 , Gota , Humanos , Ácido Úrico , Supressores da Gota/uso terapêutico , Estudos Transversais , Autoeficácia , Depressão/epidemiologia , População do Leste Asiático , Pandemias , Adesão à Medicação , Gota/tratamento farmacológico , Gota/epidemiologia , Ansiedade/epidemiologiaRESUMO
Photocatalysis is a hopeful technology to solve various environmental problems, but it is still a technical task to produce large-scale photocatalysts in a simple and sustainable way. Here, nano-flower ß-Bi2O3/TiO2 composites were prepared via a facile solvothermal method, and the photocatalytic performances of ß-Bi2O3/TiO2 composites with different Bi/Ti molar ratios were studied. The nano-flower Bi2O3/TiO2 composites were studied by SEM, XRD, XPS, BET, and PL. The PL result proved that the construction of staggered heterojunction enhanced the separation efficiency of carriers. The degradation RhB was applied to study the photocatalytic performances of prepared materials. The results showed that the degradation efficiency of RhB increased from 61.2% to 99.6% when the molar ratio of Bi/Ti was 2.1%. It is a mesoporous approach to enhance photocatalytic properties by forming heterojunction in Bi2O3/TiO2 composites, which increases the separation efficiency of the generated carriers and improves photocatalytic properties. The photoactivity of the Bi2O3/TiO2 has no evident changes after the fifth recovery, indicating that the Bi2O3/TiO2 composite has distinguished stability.
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Bismuto , Titânio , CatáliseRESUMO
The asynchronous nature of optical camera communication makes uncertain sampling a fundamental and inevitable problem that degrades data transmission performance. Based on a parametric model describing the exposure effect of the camera-based channel as the source of uncertain sampling, a simple channel equalization method and implementation are proposed in this paper to mitigate the uncertain sampling by exploiting the space-time relationship of the transmitted spatial delayed pulse width modulation waveform on multiple light sources. In addition, the rate of equalization error caused by under-sampling and over-exposure is analyzed for different duty cycles and exposure times. Numerical simulation and experiment results demonstrate the availability and reliability in mitigating uncertain sampling by the proposed channel equalization.
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Goaf filling is an effective method of preventing goaf disasters in mines. If the filling material can mineralize and absorb a large amount of CO2, then the goaf will provide a huge amount of space for carbon storage, which will help to achieve carbon peaking and carbon neutrality. The purpose of this article is to prepare a kind of porous particle with high porosity and a large specific surface area that can be used to fill the mined-out area and adsorb a large amount of CO2 by using the mineralized solid waste as the aggregate. Taking the compressive strength and CO2 adsorption capacity as the objective function, a chemical foaming method and an orthogonal experiment were used to determine the optimal ratio of porous particles. The results showed that when the masses of carbide slag, oleic acid, cetyltrimethylammonium bromide, sodium hypochlorite, and water were 19.5, 0.3, 0.07, 1.35, and 15 g, respectively, the pore sizes of the prepared porous particles had a gradient distribution, i.e., micropores, mesopores, and macropores accounted for 18.75, 80.93, and 0.32%, respectively. In addition, the compressive strength reached 79.4 N, and the static CO2 adsorption capacity was 117.43 cm3/g. The superimposed calculation of the adsorption capacity and mineralization capacity showed that 1 ton of solid waste can theoretically store approximately 0.66 ton of CO2. The pseudo-first-order kinetic model can well fit the adsorption process of an adsorbent for CO2, which proves that the adsorption process of adsorbent for CO2 is a physical adsorption mechanism. The porous particles prepared based on solid waste are harmless and simple in the preparation process. They can fill the underground space of mines after adsorbing CO2 and realize the integration of solid waste utilization, carbon storage, and underground space disaster management, with significant social, economic, and ecological benefits.
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INTRODUCTION: A genome-wide association analysis revealed a rheumatoid arthritis (RA)-risk-associated genetic locus on chromosome 9, which contained the tumor necrosis factor receptor-associated factor 1 (TRAF1). However, the detail mechanism by TRAF1 signaled to fibroblast-like synoviocytes (FLSs) apoptosis remains to be fully understood. MATERIALS AND METHODS: Synovial tissue of 10 RA patients and osteoarthritis patients were obtained during joint replacement surgery. We investigated TRAF1 level and FLSs apoptosis percentage in vivo and elucidated the mechanism involved in the regulation of apoptotic process in vitro. RESULTS: We proved the significant increase of TRAF1 level in FLSs of RA patients and demonstrated that TRAF1 level correlated positively with DAS28 score and negatively with FLSs apoptosis. Treatment with siTRAF1 was able to decrease MMPs levels and the phosphorylated forms of JNK/NF-κB in vitro. Moreover, JNK inhibitor could attenuate expression of MMPs and increase percentage of apoptosis in RA-FLSs, while siTRAF1 could not promote apoptosis when RA-FLSs were pretreated with JNK activator. CONCLUSIONS: High levels of TRAF1 in RA synovium play an important role in the synovial hyperplasia of RA by suppressing apoptosis through activating JNK/NF-kB-dependent signaling pathways in response to the engagement of CD40.
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Artrite Reumatoide , Antígenos CD40/metabolismo , Sinoviócitos , Apoptose , Artrite Reumatoide/metabolismo , Proliferação de Células , Células Cultivadas , Fibroblastos/metabolismo , Estudo de Associação Genômica Ampla , Humanos , MAP Quinase Quinase 4/metabolismo , NF-kappa B/metabolismo , Membrana Sinovial/patologia , Sinoviócitos/metabolismo , Fator 1 Associado a Receptor de TNF/genética , Fator 1 Associado a Receptor de TNF/metabolismoRESUMO
The characteristics of a rolling shutter in a commonly used complementary metal-oxide-semiconductor (CMOS) camera are important for the demodulation of an undersampled OOK symbol in optical camera communication (OCC). Therefore, a parametric model is proposed to analytically characterize the rolling shutter transfer function that converts the intensity of the light source to the brightness of the output image using several parameters. To validate the model, an effective sampling technique was used to measure the rolling shutter effect using a low-frame-rate CMOS camera. The model and results provided insights into the threshold adaptation and error performance analysis of OCC using undersampled modulation.
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PURPOSE: To compare the effects of deep learning image reconstruction (DLIR) and adaptive statistical iterative reconstruction V (ASiR-V) on image quality in low-dose computed tomography (CT) of paranasal sinuses in children. METHODS: Low-dose CT scans of the paranasal sinuses in 25 pediatric patients were retrospectively evaluated. The raw data were reconstructed with three levels of DLIR (high, H; medium, M; and low, L), filtered back projection (FBP), and ASiR-V (30% and 50%). Image noise was measured in both soft tissue and bone windows, and the signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) of the images were calculated. Subjective image quality at the ethmoid sinus and nasal cavity levels of the six groups of reconstructed images was assessed by two doctors using a five-point Likert scale in a double-blind manner. RESULTS: The patients' mean dose-length product and effective dose were 36.65 ± 2.44 mGy·cm and 0.17 ± 0.03 mSv, respectively. (1) Objective evaluation: 1. Soft tissue window: The difference among groups in each parameter was significant (P < 0.05). Pairwise comparisons showed that the H group' s parameters were significantly better (P < 0.05) than those of the 50% post-ASiR-V group. 2. Bone window: No significant between-group differences were found in the noise of the petrous portion of the temporal bone or its SNR or in the noise of the pterygoid processes of the sphenoids or their SNRs (P > 0.05). Significant differences were observed in the background noise and CNR (P < 0.05). As the DLIR intensity increased, image noise decreased and the CNR improved. The H group exhibited the best image quality. (2) Subjective evaluation: Scores for images of the ethmoid sinuses were not significantly different among groups (P > 0.05). Scores for images of the nasal cavity were significantly different among groups (P < 0.05) and were ranked in descending order as follows: H, M, L, 50% post-ASiR-V, 30% post-ASiR-V, and FBP. CONCLUSION: DLIR was superior to FBP and post-ASiR-V in low-dose CT scans of pediatric paranasal sinuses. At high intensity (H), DLIR provided the best reconstruction effects.
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Aprendizado Profundo , Seios Paranasais , Algoritmos , Criança , Método Duplo-Cego , Humanos , Processamento de Imagem Assistida por Computador , Seios Paranasais/diagnóstico por imagem , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
OBJECTIVES: The objective of this study is to investigate leaching residual monomer and biological effects of four types of conventional and computer-aided design/computer-aided manufacturing (CAD/CAM) dental polymers on human gingival fibroblasts (HGFs). MATERIALS AND METHODS: A total of 540 disk-shaped specimens were fabricated from four different materials (n=135 per group): compression-molding polymethylmethacrylate (PMMA) (conventional denture polymer), CAD/CAM PMMA (CAD/CAM denture polymer), bis-acrylic composite resin (conventional temporary polymer), and CAD/CAM PMMA (CAD/CAM temporary polymer). Specimens were eluted in cell culture medium for 72 h at 37°C, and the residual monomer in eluates subsequently was measured by high-performance liquid chromatography (HPLC). The biological effects of material eluates on HGFs were analyzed by CCK-8 assay, flow cytometry, real-time quantitative PCR, Western blotting, and enzyme-linked immunosorbent assay (ELISA) to identify cell death patterns and its biological mechanism. RESULTS: Methyl methacrylate (MMA) was detected only in compression-molding PMMA, and by-products were detected in bis-acrylic composite resin. The cell proliferation of CAD/CAM denture polymer or CAD/CAM temporary polymer was greater than that of compression-molding PMMA or bis-acrylic composite resin at 72 h in culture. No apoptosis and necrosis were detected in CAD/CAM dental polymers. Apoptosis was detected only in bis-acrylic composite resin and further confirmed by the upregulation of Bax and cleaved Caspase-3, as well as the downregulation of Bcl-2 gene. And no significant variation in inflammatory cytokines secretion was observed in all materials. CONCLUSIONS: CAD/CAM dental polymers (including temporary and denture polymers) have favorable biocompatibility due to lower residual monomer, which provides scientific evidence to the controversy of biocompatibility of conventional and CAD/CAM dental polymers. CLINICAL RELEVANCE: The use of CAD/CAM dental polymers is recommended in the fabrication of temporary restorations and dentures due to their favorable biocompatibility.
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Desenho Assistido por Computador , Polímeros , Resinas Compostas/farmacologia , Materiais Dentários/química , Materiais Dentários/farmacologia , Humanos , Teste de Materiais , Polímeros/química , Polímeros/farmacologia , Polimetil Metacrilato/farmacologia , Propriedades de SuperfícieRESUMO
PURPOSE: An investigation of arthroscopic surgery combined with coverage of the microfractured wound surface with platelet-rich plasma (PRP) and fibrin gels (FG) to treat knee cartilage defects. METHODS: Between February 2017 and February 2020, 145 patients with knee cartilage defects were treated. Only isolated full-thickness cartilage defects were included, and 28 patients (12 men and 16 women) were included in this study. They were all treated with arthroscopic surgery on subchondral bones, filled with PRP and thrombin, and sealed with FG. The knee pain visual analogue scale (VAS) scores were measured after the patients climbed ten stairs up and down, and the Western Ontario and McMaster Universities osteoarthritis index and the area of cartilage defects were measured through the pre-operative and post-operative follow-up. The complication incidences were also observed. RESULTS: All patients were followed up for ten to 15 months (median 12 months). The knee pain VAS scores decreased from 6.57 ± 1.07 pre-operatively to 2.09 ± 1.35 at the last follow-up. The WOMAC osteoarthritis index decreased from 44.32 ± 3.95 (mean ± sd) pre-operatively to 16.57 ± 2.20 by the last follow-up. The cartilage defect decreased from 2.93 ± 0.65 cm2 pre-operatively to 1.09 ± 0.69 cm2 at the last follow-up. All scores showed statistically significant improvements after surgery (p < 0.05). No complications were observed. CONCLUSION: The combination therapy of arthroscopic surgery and covering the microfractured wound surface with PRP and FG can repair knee cartilage defects, relieve pain, and improve function, and is a safe and effective treatment.
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Doenças das Cartilagens , Cartilagem Articular , Fraturas de Estresse , Osteoartrite do Joelho , Plasma Rico em Plaquetas , Artroscopia , Doenças das Cartilagens/cirurgia , Cartilagem Articular/cirurgia , Feminino , Fibrina , Géis , Humanos , Imageamento por Ressonância Magnética , Masculino , Osteoartrite do Joelho/cirurgia , Osteoartrite do Joelho/terapia , Dor , Resultado do TratamentoRESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to be a major public health challenge globally. The identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived T-cell epitopes is of critical importance for peptide vaccines or diagnostic tools of COVID-19. METHODS: In this study, several SARS-CoV-2-derived human leukocyte antigen (HLA)-I binding peptides were predicted by NetMHCpan-4.1 and selected by Popcover to achieve pancoverage of the Chinese population. The top 5 ranked peptides derived from each protein of SARS-CoV-2 were then evaluated using peripheral blood mononuclear cells from unexposed individuals (negative for SARS-CoV-2 immunoglobulin G). RESULTS: Seven epitopes derived from 4 SARS-CoV-2 proteins were identified. It is interesting to note that most (5 of 7) of the SARS-CoV-2-derived peptides with predicted affinities for HLA-I molecules were identified as HLA-II-restricted epitopes and induced CD4+ T cell-dependent responses. These results complete missing pieces of pre-existing SARS-CoV-2-specific T cells and suggest that pre-existing T cells targeting all SARS-CoV-2-encoded proteins can be discovered in unexposed populations. CONCLUSIONS: In summary, in the current study, we present an alternative and effective strategy for the identification of T-cell epitopes of SARS-CoV-2 in healthy subjects, which may indicate an important role in the development of peptide vaccines for COVID-19.
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Vacinas contra COVID-19/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Epitopos de Linfócito T/imunologia , Vacinas de Subunidades Antigênicas/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular , Humanos , Leucócitos Mononucleares/imunologia , SARS-CoV-2RESUMO
Adoptive transfer of T cells genetically engineered with a T cell receptor (TCR) is a promising cancer treatment modality that requires the identification of TCRs with good characteristics. Most T cell cloning methods involve a stringent singularization process, which necessitates either tedious hands-on operations or high cost. We present an efficient and nonstringent cloning approach based on existing techniques. We hypothesize that after elimination of most nonspecific T cells, a clonotype with high quality could outcompete other clonotypes and finally form a predominant population. This TCR identification method can be used to clone virus-specific TCRs efficiently from cancer patients and is easily adoptable by any laboratory.
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Imunoterapia Adotiva/métodos , Neoplasias/imunologia , Neoplasias/terapia , Vírus Oncogênicos/fisiologia , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T/imunologia , Viroses/imunologia , Linhagem Celular , Células Clonais , Citometria de Fluxo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T/transplanteRESUMO
Stringent control of NF-κB and mitogen-activated protein kinase (MAPK) signaling is critical during innate immune responses. TGF-ß activated kinase-1 (TAK1) is essential for NF-κB activation in T and B cells but has precisely the opposite activity in myeloid cells. Specific deletion of TAK1 (Map3k7(ΔM/ΔM)) led to development of splenomegaly and lymphomegaly associated with neutrophilia. Compared with wild-type cells, TAK1-deficient neutrophils enhanced the phosphorylation of the kinases IKK, p38, and JNK and the production of interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), and reactive oxygen species (ROS) after lipopolysaccharide (LPS) stimulation. Map3k7(ΔM/ΔM) mice were significantly more susceptible to LPS-induced septic shock and produced higher amounts of IL-1ß, IL-6, and TNF-α in plasma than do wild-type mice. Specific ablation of p38 rescued the phenotype and functional properties of Map3k7(ΔM/ΔM) mice. Our findings identify a previously unrecognized role of TAK1 as a negative regulator of p38 and IKK activation in a cell type-specific manner.