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Perception of pathogen-associated molecular patterns (PAMPs) by plant cell surface-localized pattern-recognition receptors (PRRs) triggers the first line of plant innate immunity. In Arabidopsis thaliana, the receptor-like cytoplasmic kinase BRASSINOSTEROID-SIGNALING KINASE1 (BSK1) physically associates with PRR FLAGELLIN SENSING2 and plays an important role in defense against multiple pathogens. However, how BSK1 transduces signals to activate downstream immune responses remains elusive. Previously, through whole-genome phosphorylation analysis using mass spectrometry, we showed that phosphorylation of the mitogen-activated protein kinase (MAPK) MPK15 was affected in the bsk1 mutant compared with the wild-type plants. Here, we demonstrated that MPK15 is important for powdery mildew fungal resistance. PAMPs and fungal pathogens significantly induced the phosphorylation of MPK15 Ser-511, a key phosphorylation site critical for the functions of MPK15 in powdery mildew resistance. BSK1 physically associates with MPK15 and is required for basal and pathogen-induced MPK15 Ser-511 phosphorylation, which contributes to BSK1-mediated fungal resistance. Taken together, our data identified MPK15 as a player in plant defense against powdery mildew fungi and showed that BSK1 promotes fungal resistance in part by enhancing MPK15 Ser-511 phosphorylation. These results uncovered a mechanism of BSK1-mediated disease resistance and provided new insight into the role of MAPK phosphorylation in plant immunity.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/química , Brassinosteroides/metabolismo , Resistência à Doença/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Moléculas com Motivos Associados a Patógenos/metabolismo , Fosforilação , Doenças das Plantas/microbiologia , Imunidade Vegetal/genética , Proteínas Serina-Treonina Quinases/genéticaRESUMO
G-quadruplex (G4)/hemin DNAzyme is a promising candidate to substitute horseradish peroxidase in biosensing systems, especially for the detection of nucleic acids. However, the relatively suboptimal catalytic capacity limits its potential applications. This makes it imperative to develop an ideal signal for the construction of highly sensitive biosensing platforms. Herein, we integrated a novel chimeric peptide-DNAzyme (CPDzyme) with the ligase chain reaction (LCR) for the cost-efficient and highly sensitive detection of nucleic acids. By employing microRNA (miRNA) and single-nucleotide polymorphism detection as the model, we designed a G4-forming sequence on the LCR probe with a terminally labeled amino group. Subsequently, asymmetric hemin with carboxylic arms allowed assembly with the LCR products and peptide to form CPDzyme, followed by the magnetic separation of the extraneous components and chemiluminescence detection. Compared with the conventional G4/hemin signaling-based method, the LCR-CPDzyme system demonstrated 3 orders of magnitude improved sensitivity, with accurate quantification of as low as 25 aM miRNA and differentiation of 0.1% of mutant DNA from the pool containing a large amount of wild-type DNA. The proposed LCR-CPDzyme strategy is a potentially powerful method for in vitro diagnostics and serves as a reference for the development of other ligation- or hybridization-based nucleic acid amplification assays.
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Técnicas Biossensoriais , DNA Catalítico , Quadruplex G , MicroRNAs , DNA Catalítico/metabolismo , Hemina , DNA/genética , MicroRNAs/genética , Técnicas Biossensoriais/métodos , Peptídeos/genéticaRESUMO
Disease diagnostics and surveillance increasingly highlight the importance of portable, cost-effective, and sensitive point-of-care (POC) detection of nucleic acids. Here, we report a CRISPR/Cas13a-responsive and RNA-bridged DNA hydrogel capillary sensor for the direct and visual detection of specific RNA with high sensitivity. The capillary sensor was simply prepared by loading RNA-cross-linking DNA hydrogel film (â¼0.2 mm ± 0.02 mm) at the end of a capillary. When CRISPR/Cas13a specifically recognizes the target RNA, the RNA bridge in the hydrogel film is cleaved by the trans-cleavage activity of CRISPR/Cas13a, increasing the permeability of the hydrogel film. Different concentrations of target RNA activate different amounts of Cas13a, cleaving different amounts of the RNA bridge in the hydrogel and causing corresponding changes in the permeability of the hydrogel. Therefore, samples containing different amounts of the target RNA travel to different distances in the capillary. Visual reading of the distance provides quantitative detection of the RNA target without the need for any nucleic acid amplification or auxiliary equipment. The technique was successfully used for the determination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in clinical nasopharyngeal (NP) swab and saliva samples. Easily quantifiable distance using a ruler eliminates the need for any optical or electrochemical detection equipment, making this assay potentially useful for POC and on-site applications.
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Sistemas CRISPR-Cas , DNA , Hidrogéis , SARS-CoV-2 , Humanos , Hidrogéis/química , DNA/química , DNA/análise , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Sistemas Automatizados de Assistência Junto ao Leito , RNA Viral/análise , Técnicas Biossensoriais , COVID-19/diagnóstico , COVID-19/virologia , RNA/análiseRESUMO
Carbon monoxide (CO) functions as a significant endogenous cell signaling molecule and is strongly associated with many physiological and pathological processes. However, conventional fluorescence imaging in the visible and near-infrared (NIR) I regions suffers autofluorescence background and photon scattering, hindering the accurate detection of CO in vivo. In addition, the complexity of physiological environments leads to fluctuating fluorescence emission. To solve these problems, herein, the NIR-II fluorescent nanoprobe NP-Pd for in vivo ratiometric bioimaging of CO is developed. In the presence of CO, NP-Pd exhibits responsive enhancement in absorption at 808 nm, which amplifies the fluorescence signal of down-conversion nanoparticles (DCNP) at 1060 nm under 808 nm excitation, while the fluorescence signal of DCNP at 1525 nm under 980 nm excitation remains unchanged and serves as an internal standard. Through this orthogonally ratiometric fluorescence strategy, accurate CO bioimaging and precise diagnosis of acute liver injury diseases are achieved in the mouse model experiments, providing a novel tool for the in vivo detection of CO-related diseases.
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Nuclear pore complex (NPC) is composed of multiple nucleoporins (Nups). A plethora of studies have highlighted the significance of NPC in plant immunity. However, the specific roles of individual Nups are poorly understood. NUCLEAR PORE ANCHOR (NUA) is a component of NPC. Loss of NUA leads to an increase in SUMO conjugates and pleiotropic developmental defects in Arabidopsis thaliana. Herein, we revealed that NUA is required for plant defense against multiple pathogens. NUCLEAR PORE ANCHOR associates with the transcriptional corepressor TOPLESS-RELATED1 (TPR1) and contributes to TPR1 deSUMOylation. Significantly, NUA-interacting protein EARLY IN SHORT DAYS 4 (ESD4), a SUMO protease, specifically deSUMOylates TPR1. It has been previously established that the SUMO E3 ligase SAP AND MIZ1 DOMAIN-CONTAINING LIGASE 1 (SIZ1)-mediated SUMOylation of TPR1 represses the immune-related function of TPR1. Consistent with this notion, the hyper-SUMOylated TPR1 in nua-3 leads to upregulated expression of TPR1 target genes and compromised TPR1-mediated disease resistance. Taken together, our work uncovers a mechanism by which NUA positively regulates plant defense responses by coordination with ESD4 to deSUMOylate TPR1. Our findings, together with previous studies, reveal a regulatory module in which SIZ1 and NUA/ESD4 control the homeostasis of TPR1 SUMOylation to maintain proper immune output.
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Proteínas de Arabidopsis , Arabidopsis , Imunidade Vegetal , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Ligases/metabolismo , Poro Nuclear/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , SumoilaçãoRESUMO
This study aimed to evaluate the clinical efficacy of percutaneous coaxial large-channel endoscopic lumbar interbody fusion (PCLE-LIF) and transforaminal lumbar interbody fusion (TLIF) in the treatment of degenerative lumbar spinal stenosis. The clinical data of patients with degenerative lumbar spinal stenosis who underwent PCLE-LIF (experimental group) and TLIF (control group) surgery from September 2019 to September 2021 were retrospectively analyzed. We collected clinical data and compared the two groups in terms of perioperative parameters, treatment response rate, inflammatory response markers, postoperative complications, postoperative pain, and functional recovery. The results showed that the treatment outcomes in the experimental group were significantly better than those in the control group. Specifically, perioperative parameters and inflammatory response markers in the experimental group were significantly better than those in the control group, with statistically significant differences (P < 0.05). The overall treatment response rate in the experimental group was significantly higher than that in the control group (P < 0.05). Meanwhile, the incidence of postoperative complications in the experimental group was lower than that in the control group, postoperative VAS pain scores and ODI functional scores were lower, and postoperative JOA functional scores were higher than those in the control group, with statistically significant differences (P < 0.05). In conclusion, PCLE-LIF appears to be a promising technique with better clinical outcomes in the treatment of degenerative lumbar spinal stenosis.
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Endoscopia , Vértebras Lombares , Fusão Vertebral , Estenose Espinal , Humanos , Estenose Espinal/cirurgia , Estudos Retrospectivos , Masculino , Feminino , Fusão Vertebral/métodos , Fusão Vertebral/efeitos adversos , Fusão Vertebral/instrumentação , Vértebras Lombares/cirurgia , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Endoscopia/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Recuperação de Função Fisiológica , Dor Pós-Operatória/etiologia , Degeneração do Disco Intervertebral/cirurgiaRESUMO
PURPOSE: To develop a deep learning model to accurately detect anterior cruciate ligament (ACL) ruptures on magnetic resonance imaging (MRI) and to evaluate its effect on the diagnostic accuracy and efficiency of clinicians. METHODS: A training dataset was built from MRIs acquired from January 2017 to June 2021, including patients with knee symptoms, irrespective of ACL ruptures. An external validation dataset was built from MRIs acquired from January 2021 to June 2022, including patients who underwent knee arthroscopy or arthroplasty. Patients with fractures or prior knee surgeries were excluded in both datasets. Subsequently, a deep learning model was developed and validated using these datasets. Clinicians of varying expertise levels in sports medicine and radiology were recruited, and their capacities in diagnosing ACL injuries in terms of accuracy and diagnosing time were evaluated both with and without artificial intelligence (AI) assistance. RESULTS: A deep learning model was developed based on the training dataset of 22,767 MRIs from 5 centers and verified with external validation dataset of 4,086 MRIs from 6 centers. The model achieved an area under the receiver operating characteristic curve of 0.987 and a sensitivity and specificity of 95.1%. Thirty-eight clinicians from 25 centers were recruited to diagnose 3,800 MRIs. The AI assistance significantly improved the accuracy of all clinicians, exceeding 96%. Additionally, a notable reduction in diagnostic time was observed. The most significant improvements in accuracy and time efficiency were observed in the trainee groups, suggesting that AI support is particularly beneficial for clinicians with moderately limited diagnostic expertise. CONCLUSIONS: This deep learning model demonstrated expert-level diagnostic performance for ACL ruptures, serving as a valuable tool to assist clinicians of various specialties and experience levels in making accurate and efficient diagnoses. LEVEL OF EVIDENCE: Level III, retrospective comparative case series.
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Lesões do Ligamento Cruzado Anterior , Aprendizado Profundo , Humanos , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Lesões do Ligamento Cruzado Anterior/cirurgia , Ligamento Cruzado Anterior , Estudos Retrospectivos , Inteligência Artificial , Imageamento por Ressonância Magnética/métodosRESUMO
PURPOSE: This systematic review and meta-analysis aimed to evaluate the safety of outpatient and inpatient Unicompartmental Knee Arthroplasty (UKA) based on the incidence of adverse events. METHOD: A systematic search of the literature was performed in October 2022 on PubMed, Web of Science, Cochrane library, and Embase. The Meta package for R was used to perform the meta-analysis. RESULT: Five studies with a total of 26,301 patients were included. 5813 patients (22.1%) were treated with outpatient UKA, and 20,488 patients (77.9%) were treated with inpatient UKA. There were no statistically significant differences in the incidence of total complications (RR = 1.36, 95% CI = 0.64-2.89, Z = 0.79, P = 0.43), readmission (RR = 1.02, 95% CI = 0.40-2.60, Z = 0.05, P = 0.96), and venous thrombosis (RR = 1.43, 95% CI = 0.96-2.11, Z = 1.78, P = 0.08). Incidence rates were lower in outpatient UKA regarding urinary tract infection (RR = 1.48, 95% CI = 1.07-2.04, Z = 2.40, P = 0.02), pulmonary embolus (RR = 7.48, 95% CI = 1.80-31.17, Z = 2.76, P < 0.01), and transfusion (RR = 2.77, 95% CI = 1.63-4.71, Z = 3.78, P < 0.01). CONCLUSION: In summary, outpatient UKA shows lower incidences of hospital-acquired complications such urinary tract infection, pulmonary embolus, and transfusion. It's worth noting that the incidences of total complications, readmission, and venous thrombosis in outpatient UKA were not higher than the incidences of inpatient UKA, suggestting that outpatient UKA can be considered a safe alternative to inpatient UKA.
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Artroplastia do Joelho , Complicações Pós-Operatórias , Humanos , Artroplastia do Joelho/métodos , Artroplastia do Joelho/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Ambulatórios/efeitos adversos , Procedimentos Cirúrgicos Ambulatórios/métodos , Segurança do Paciente , Incidência , Readmissão do Paciente/estatística & dados numéricosRESUMO
Chimeric peptide-DNAzyme (CPDzyme) is a novel artificial peroxidase that relies on the covalent assembly of DNA, peptides, and an enzyme cofactor in a single scaffold. An accurate control of the assembly of these different partners allows for the design of the CPDzyme prototype G4-Hemin-KHRRH, found to be >2000-fold more active (in terms of conversion number kcat) than the corresponding but non-covalent G4/Hemin complex and, more importantly, >1.5-fold more active than the corresponding native peroxidase (horseradish peroxidase) when considering a single catalytic center. This unique performance originates in a series of gradual improvements, thanks to an accurate selection and arrangement of the different components of the CPDzyme, in order to benefit from synergistic interactions between them. The optimized prototype G4-Hemin-KHRRH is efficient and robust as it can be used under a wide range of non-physiologically relevant conditions [organic solvents, high temperature (95 °C), and in a wide range of pH (from 2 to 10)], thus compensating for the shortcomings of the natural enzymes. Our approach thus opens broad prospects for the design of ever more efficient artificial enzymes.
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DNA Catalítico , Quadruplex G , Peroxidase do Rábano Silvestre/metabolismo , Hemina , Peroxidase/metabolismo , Peroxidases , DNA Catalítico/metabolismo , PeptídeosRESUMO
The target-dependent endonuclease activity (also known as the trans-cleavage activity) of CRISPR-Cas systems has stimulated great interest in the development of nascent sensing strategies for nucleic acid diagnostics. Despite many attempts, the majority of the sensitive CRISPR-Cas diagnostics strategies mainly rely on nucleic acid preamplification, which generally needs complex probes/primers designs, multiple experimental steps, and a longer testing time, as well as introducing the risk of false-positive results. In this work, we propose the CRISPR-Cas-Driven Single Micromotor (Cas-DSM), which can directly detect the nucleic acid targets at a single-molecule level with high specificity. We have demonstrated that the Cas-DSM is a reliable and practical method for the quantitative detection of DNA/RNA in various complex clinical samples as well as in individual cells without any preamplification processes. Due to the excellent features of the CRISPR/Cas system, including constant temperature, simple design, high specificity, and flexible programmability, the Cas-DSM could serve as a simple and universal platform for nucleic acid detection. More importantly, this work will provide a breakthrough for the development of next-generation amplification-free CRISPR/Cas sensing toolboxes.
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Técnicas Biossensoriais , Ácidos Nucleicos , Sistemas CRISPR-Cas/genética , RNA , Biomarcadores , Primers do DNARESUMO
A simultaneous magnetic field and temperature sensing scheme based on cascaded microwave photonic filters (MPFs) with high resolution is proposed and experimentally demonstrated. A polarization maintaining fiber bonded with a giant magnetostrictive material acts both as a magnetic field sensing probe and an important unit of a dispersion-induced MPF. A 500 m single mode fiber in a two-tap MPF is used to perform temperature compensation. The power fading frequency of the dispersion-induced MPF and the dip frequency of the two-tap MPF are selected to monitor the magnetic field and temperature changes. When temperature changes, both power fading frequency and dip frequency will change. While only power fading frequency shifts as magnetic field changes. Consequently, dual parameter sensing can be achieved by monitoring the characteristic microwave frequencies of the two MPFs. The temperature cross-sensitivity is well resolved in this way. In the experiment, the microwave frequency changes 5.84â MHz as external magnetic field increases by 1â mT. The corresponded theoretical resolution can reach 0.17 nT, which is only limited by the minimum resolution of vector network analyzer.
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A novel photonic method for multi-format chirped signal generation with a high switching rate based on a dual-polarization binary phase shift keying (DP-BPSK) modulator is proposed and demonstrated. An up-chirp signal and a binary code signal are used to drive one of the sub-dual-drive Mach-Zehnder modulators (sub-DDMZMs) integrated in the DP-BPSK modulator. Another integrated sub-DDMZM is driven by a down-chirp signal and another binary code signal. By carefully tuning the DC biases of the DP-BPSK modulator, the format of the output chirped signal is controlled by the binary code signals. A proof-of-concept experiment is performed and multi-format chirped signals with a high switching rate are generated. Due to the high switching rate, simple structure, and high adjustability, the proposed multi-format chirped signal generator may find potential applications in multifunctional radar systems, wireless communication systems, and dual-function radar-communication systems.
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BACKGROUND: Radiomics-based preoperative evaluation of lymph node metastasis (LNM) and histological grade (HG) might facilitate the decision-making for pancreatic cancer and further efforts are needed to develop effective models. PURPOSE: To develop multiparametric MRI (MP-MRI)-based radiomics models to evaluate LNM and HG. STUDY TYPE: Retrospective. POPULATION: The pancreatic cancer patients from the main center (n = 126) were assigned to the training and validation sets at a 4:1 ratio. The patients from the other center (n = 40) served as external test sets. FIELD STRENGTH/SEQUENCE: A 3.0 T and 1.5 T/T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast enhancement T1-weighted imaging. ASSESSMENT: A total of 10,686 peritumoral and intratumoral radiomics features were extracted which contained first-order, shape-based, and texture features. The following three-step method was applied to reduce the feature dimensionality: SelectKBest (a function from scikit-learn package), least absolute shrinkage and selection operator (LASSO), and recursive feature elimination based on random forest (RFE-RF). Six classifiers (random forest, logistic regression, support vector machine, K-nearest neighbor, decision tree, and XGBOOST) were trained and selected based on their performance to construct the clinical, radiomics, and combination models. STATISTICAL TESTS: Delong's test was used to compare the models' performance. P value less than 0.05 was considered significant. RESULTS: Twelve significant features for LNM and 11 features for HG were obtained. Random forest and logistic regression performed better than the other classifiers in evaluating LNM and HG, respectively, according to the surgical pathological results. The best performance was obtained with the models that combined peritumoral and intratumoral features with area under curve (AUC) values of 0.944 and 0.892 in the validation and external test sets for HG and 0.924 and 0.875 for LNM. DATA CONCLUSION: Radiomics holds the potential to evaluate LNM and HG of pancreatic cancer. The combination of peritumoral and intratumoral features will make models more accurate. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.
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Metástase Linfática , Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias Pancreáticas , Humanos , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Imageamento por Ressonância Magnética , Metástase Linfática/patologia , Radiômica , Estudos RetrospectivosRESUMO
BACKGROUND: Low-molecular-weight heparin (LMWH) and fondaparinux sodium (FPX) are routinely used to prevent deep vein thrombosis (DVT) after total knee arthroplasty (TKA). In this study, we compared the effects of these agents in preventing post-TKA DVT. METHODS: Clinical data of patients who underwent unilateral TKA for unicompartmental knee osteoarthritis at the Ningxia Medical University General Hospital between September 2021 and June 2022 were retrospectively analyzed. Based on the anticoagulation agent used, the patients were divided into LMWH and FPX groups (34 and 37 patients, respectively). Changes in perioperative coagulation-related indicators, d-dimer and platelet count, perioperative complete blood count, amount of blood loss, lower-limb DVT, pulmonary embolism, and allogeneic blood transfusion were determined. RESULTS: Intergroup differences in d-dimer or fibrinogen (FBG) levels before and 1 or 3 days after surgery were not significant (all p > 0.05); within-group pairwise comparisons indicated significant differences (all, p < 0.05). Intergroup differences in preoperative prothrombin time (PT), thrombin time, activated partial PT, and international normalized ratio were not significant (all p > 0.05), whereas significant differences were detected on postoperative days 1 and 3 (all p < 0.05). Intergroup differences in platelet counts before and 1 or 3 days after surgery were not significantly different (all p > 0.05). Pairwise comparisons of hemoglobin and hematocrit levels between patients in the same group before and 1 or 3 days after surgery revealed significant differences in both groups (all p < 0.05); however, intergroup differences were not significant (all p > 0.05). Although intergroup differences in visual analog scale (VAS) scores before and 1 or 3 days after surgery were not significant (p > 0.05), we detected significant intragroup differences in VAS scores before and 1 or 3 days after surgery (p < 0.05). The treatment cost ratio was significantly lower in the LMWH group than in the FPX group (p < 0.05). CONCLUSION: Both LMWH and FPX can effectively prevent DVT after TKA. There are some suggestive signals that FPX may have more beneficial pharmacological effects and clinical significance, while LMWH is cheaper and therefore more economical.
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Artroplastia do Joelho , Heparina de Baixo Peso Molecular , Humanos , Heparina de Baixo Peso Molecular/uso terapêutico , Fondaparinux/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Anticoagulantes/uso terapêutico , Estudos RetrospectivosRESUMO
Aberrant transmembrane protein (TMEM) expression is implicated in tumor progression, but its functional role in hepatocellular carcinoma (HCC) is unclear. Thus, we aim to characterize the functional contributions of TMEM in HCC. In this study, four novel TMEM-family genes (TMEMs), TMEM106C, TMEM201, TMEM164, and TMEM45A, were screened to create a TMEMs signature. These candidate genes are distinguished between patients with varying survival statuses. High-risk HCC patients had a significantly worse prognosis and more advanced clinicopathological characteristics in both the training and validation groups. The GO and KEGG analyses unveiled that the TMEMs signature might play a crucial role in cell-cycle-relevant and immune-related pathways. We found that the high-risk patients had lower stromal scores and a more immunosuppressive tumor microenvironment with massive infiltration of macrophages and Treg cells, whereas the low-risk group had higher stromal scores and gamma delta T-cell infiltration. Moreover, the expression level of suppressive immune checkpoints increased as the TMEM-signature scores increased. Furthermore, the in vitro experiments validated TMEM201, one feature of the TMEMs signature, and facilitated HCC proliferation, survival, and migration. The TMEMs signature provided a more precise prognostic evaluation of HCC and reflected the immunological status of HCC. Of the TMEMs signature studied, TMEM201 was found to significantly promote HCC progression.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteínas de Membrana , Humanos , Carcinogênese , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Ciclo Celular , Relevância Clínica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Microambiente Tumoral/genética , Proteínas de Membrana/genéticaRESUMO
House dust mites (HDMs) are a potent allergen source that are commonly found in human living environments. While HDMs are known to induce allergic diseases in humans, such as asthma, its other biological activities related to human health are less understood. Our laboratory recently purified the HDM protein PDI (protein disulfide isomerase). In this study, we assess the role of PDI in contributing to immune regulation. Using mass spectrometry, we analyzed the complexes of DEC205 and HDM extracts, and the role of PDI in the induction of tolerogenic dendritic cells (DCs) was assessed in human cell culture experiments and verified in a murine model. We found that more than 20 HDM-derived proteins, including PDI, bound to DCs by forming complexes with DEC205. Additionally, DEC205-mediated the endocytosis of PDI. HDM-derived PDI (HDM-PDI) promoted Foxp3 expression in DCs. HDM-PDI-primed DCs also showed tolerogenic properties that induced regulatory T cell development, indicating that the primed DCs were tolerogenic DCs. Our results suggested that the PDI/DEC205/TIEG1/Foxp3 signal pathway activation was involved in the HDM-PDI-induced Foxp3 expression in DCs. Finally, we found that HDM-PDI competitively counteracted the Th2 cytokines to restore DC's tolerogenicity, and administration of HDM-PDI could suppress experimental asthma. In conclusion, our data suggest that HDM-PDI contributes to immune regulation by inducing tolerogenic DC development. Administration of HDM-PDI can alleviate experimental asthma. These findings demonstrate that HDM-PDI has translational potential to be used in the treatment of immune disorders such as asthma.
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Células Dendríticas/imunologia , Hipersensibilidade/terapia , Isomerases de Dissulfetos de Proteínas/metabolismo , Pyroglyphidae/enzimologia , Sistema Respiratório/imunologia , Animais , Citocinas/metabolismo , Células Dendríticas/metabolismo , Hipersensibilidade/imunologia , Hipersensibilidade/metabolismo , CamundongosRESUMO
High-performance demodulation of Sagnac effect is of great importance for rotation rate measurement in inertial navigation system. In this paper, we propose a flexible measurement of rotation rate based on a phase-controlled microwave photonic filter (MPF), which incorporates an orthogonal double-sideband (ODSB) modulator, a Sagnac loop, a linearly chirped fiber Bragg grating (LCFBG), a polarizer, and a photodetector. The ODSB modulator is used to generate optical carrier (OC) and first-order sidebands with mutually orthogonal polarizations. For the MPF, its central frequency can be tuned through changing the phase difference between the OC and first-order sidebands thanks to the dispersion of the LCFBG. Therefore, if the OC and first-order sidebands are separated by a polarization beam splitter and then travel along the Sagnac loop in opposite directions, the rotation-induced phase difference between them will lead to a shift on the frequency response of the MPF. Thus, two ways can be adopted to detect the rotation rate of the Sagnac loop for different applications: monitoring the frequency response shift of the MPF and measuring the power variation at a certain frequency. Besides, the measurement sensitivity can be easily adjusted to satisfy specific requirements by tuning a polarization controller or choosing a different operating frequency. An experiment is performed to validate the proposed scheme. The results show that the maximum frequency shift of the MPF can reach 1.7 GHz at a rotation rate of 1 rad/s, and a scale factor of 0.016 mW/(rad/s) is obtained at 4 GHz.
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In this paper, we propose and demonstrate a novel, to the best of knowledge, filter-free photonics-assisted microwave frequency translator with a tunable phase shift and amplitude. The pivotal component of the proposed scheme is an integrated dual-polarization quadrature phase shift keying (DP-QPSK) modulator, which is applied to generate a polarization orthogonal carrier-suppressed single sideband modulation signal and frequency shifted optical carrier signal. The polarization-multiplexed optical signal outputs from the DP-QPSK modulator is then sent to a photodetector (PD) via a polarization controller (PC) and a polarizer to implement photoelectric conversion. The electrical signal output from the PD is the desired frequency translated microwave signal, and the amount of frequency shift is determined by the frequency of the sawtooth wave applied to the DP-QPSK modulator. In addition, since the PC can be used to adjust the polarization angle and introduce a phase difference between the two orthogonally polarized optical signals, the phase shift and amplitude of the obtained translated signal can also be easily tuned. A theoretical analysis and simulation experiment are carried out to verify the feasibility of the proposed scheme. The simulation results show that the novel scheme can realize frequency translation with a 360° continuously tunable phase shift and adjustable amplitude for both a single-tone signal and linearly frequency modulated signal with a 50 MHz bandwidth. The spurious suppression ratios of the single-tone signal and LFM signal after frequency translation are larger than 48 and 30 dB, respectively.
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BACKGROUND: The optimal width of resection margin (RM) for hepatocellular carcinoma (HCC) remains controversial. This study aimed to investigate the value of imaging tumor capsule (ITC) and imaging tumor size (ITS) in guiding RM width for patients with HCC. METHODS: Patients who underwent hepatectomy for HCC in our center were retrospectively reviewed. ITC (complete/incomplete) and ITS (≤ 3 cm/> 3 cm) were assessed by preoperative magnetic resonance imaging (MRI). Using subgroup analyses based on ITC and ITS, the impact of RM width [narrow RM (< 5 mm)/wide RM (≥ 5 mm)] on recurrence-free survival (RFS), overall survival (OS), and RM recurrence was analyzed. RESULTS: A total of 247 patients with solitary HCC were included. ITC and ITS were independent predictors for RFS and OS in the entire cohort. In patients with ITS ≤ 3 cm, neither ITC nor RM width showed a significant impact on prognosis, and the incidence of RM recurrence was comparable between the narrow RM and wide RM groups (15.6% vs. 4.3%, P = 0.337). In patients with ITS > 3 cm and complete ITC, the narrow RM group exhibited comparable RFS, OS, and incidence of RM recurrence with the wide RM group (P = 0.606, 0.916, and 0.649, respectively). However, in patients with ITS > 3 cm and incomplete ITC, the wide RM group showed better RFS and OS and a lower incidence of RM recurrence compared with the narrow RM group (P = 0.037, 0.018, and 0.046, respectively). CONCLUSIONS: As MRI-based preoperative markers, conjoint analysis of ITC with ITS aids in determining RM width for solitary HCC patients. Narrow RM is applicable in patients with ITS ≤ 3 cm regardless of ITC status and in those with ITS > 3 cm and complete ITC. Wide RM is preferred in those with ITS > 3 cm and incomplete ITC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Margens de Excisão , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Hepatectomia/efeitos adversos , Hepatectomia/métodos , PrognósticoRESUMO
Agricultural robots are one of the important means to promote agricultural modernization and improve agricultural efficiency. With the development of artificial intelligence technology and the maturity of Internet of Things (IoT) technology, people put forward higher requirements for the intelligence of robots. Agricultural robots must have intelligent control functions in agricultural scenarios and be able to autonomously decide paths to complete agricultural tasks. In response to this requirement, this paper proposes a Residual-like Soft Actor Critic (R-SAC) algorithm for agricultural scenarios to realize safe obstacle avoidance and intelligent path planning of robots. In addition, in order to alleviate the time-consuming problem of exploration process of reinforcement learning, this paper proposes an offline expert experience pre-training method, which improves the training efficiency of reinforcement learning. Moreover, this paper optimizes the reward mechanism of the algorithm by using multi-step TD-error, which solves the probable dilemma during training. Experiments verify that our proposed method has stable performance in both static and dynamic obstacle environments, and is superior to other reinforcement learning algorithms. It is a stable and efficient path planning method and has visible application potential in agricultural robots.