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Several observational studies have reported an association between obesity and primary liver cancer (PLC), while the causality behind this association and the comparison of the risk effects of different obesity indicators on PLC remain unclear. In this study, we performed two-sample Mendelian randomization (MR) analyses to assess the associations of genetically determined liver fat, visceral adipose tissue (VAT), and body mass index (BMI) with the risk of PLC. The summary statistics of exposures were obtained from two genome-wide association studies (GWASs) based on the UK Biobank (UKB) imaging cohort and the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. GWAS summary statistics for PLC were obtained from FinnGen consortium R7 release data, including 304 PLC cases and 218 488 controls. Inverse-variance weighted (IVW) was used as the primary analysis, and a series of sensitivity analyses were performed to further verify the robustness of these findings. IVW analysis highlighted a significant association of genetically determined liver fat (OR per SD increase: 7.14; 95% CI: 5.10-9.99; P = 2.35E-30) and VAT (OR per SD increase: 5.70; 95% CI: 1.32-24.72; P = .020) with PLC but not of BMI with PLC. The findings were further confirmed by a series of MR methods. No evidence of horizontal pleiotropy between these associations existed. Our study suggested that genetically determined liver fat and VAT rather than BMI were associated with an increased risk of PLC, which suggested that visceral fat distribution is more predictive of the clinical risk of PLC than common in vitro measures.
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Estudo de Associação Genômica Ampla , Neoplasias Hepáticas , Adulto , Humanos , Análise da Randomização Mendeliana , Obesidade/complicações , Obesidade/genética , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Near-infrared (NIR) luminescent lanthanide materials hold great promise for bioanalysis, as they have anti-interference properties. The approach of efficient luminescence is sensitization through a reasonable chromophore to overcome the obstacle of the aqueous phase. The involvement of the surfactant motif is an innovative strategy to arrange the amphiphilic groups to be regularly distributed near the polymer to form a closed sensitized space. Herein, a lanthanide polymer (TCPP-PEI70K-FITC@Yb/SDBS) is designed in which the meso-tetra(4-carboxyphenyl)porphine (TCPP) ligand serves as both a sensitizer and photocatalytic switch. The surfactant sodium dodecyl benzenesulfonate (SDBS) wraps the photosensitive polymers to form a hydrophobic layer, which augments the light-harvesting ability and expedites its photocatalysis. TCPP-PEI70K-FITC@Yb/SDBS is subsequently applied as an amplified photocatalysis toolbox for universally regulating the generation of reactive oxygen species (ROS). Boosting 3,3',5,5'-tetramethylbenzidine (TMB) oxidation to produce blue products, a dual-mode biosensor is fabricated for improving the diagnosis of programmed death ligand-1-positive (PDL1) cancer exosomes. Exosomes were captured by Fe3O4 modified by the PDL1 aptamer, enabling replacement of alkaline phosphatase (ALP)-labeled multiple hybridized chains; then, the isolated ALP triggered a hydrolysis reaction to block the generation of oxTMB. Detection sensitivity improves by 1 order of magnitude through SDBS modulation, down to 104 particles/mL. The sensor performed well clinically in distinguishing cancer patients from healthy individuals, expanding physiological applications of near-infrared lanthanide luminescence.
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Elementos da Série dos Lantanídeos , Luz , Polímeros , Humanos , Elementos da Série dos Lantanídeos/química , Polímeros/química , Catálise , Exossomos/química , Exossomos/metabolismo , Raios Infravermelhos , Neoplasias/diagnóstico , Processos Fotoquímicos , Técnicas Biossensoriais , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismoRESUMO
Designing lanthanide luminescence lifetime sensors in the second near-infrared (NIR-II) window holds great potentials for physiological studies. However, the single lifetime signal is confined to one or two orders of magnitude of signal variation, which limits the sensitivity of lifetime probes. In this study, a lifetime cascade system, i.e., ZGO:Mn, Eu-DNA-1/TCPP-PEI70K@Yb-AptEpCAM, with a variety of signals (τm, τn, τµ, τm/τn and τm/τµ) is constructed for exosome identification using time-domain multiplexing. The sensitized ligand TCPP acts as both target-modulated switch and a bridge for connecting long lifetime ZGO:Mn, Eu-DNA-1 emitter to lanthanide Yb3+. This drives successive dual-path energy transfer and forms two D(donor)-A(acceptor) pairs. The lifetime variation is dominantly modulated by arranging TCPP as energy intermediate relay to covert milliseconds to nanoseconds to microseconds. It enables a broad lifetime range of six orders of magnitude. The presence of exosome specifically recognizes aptamers on TCPP-PEI70K@Yb-AptEpCAM to impede D-A pairs and reverse multiplexed response signals of the lifetime cascade system. The ratio lifetime signals τm/τn and τm/τµ achieve prominent exosome quantification and exosome type differentiation attributed to signal amplification. The cascade system relying on lifetime criteria can realize precise quantization and provide an effective strategy for subsequent physiological study.
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Exossomos , Elementos da Série dos Lantanídeos , Elementos da Série dos Lantanídeos/química , Exossomos/metabolismo , Exossomos/química , Humanos , Transferência de Energia , Neoplasias/metabolismoRESUMO
The Nrf2/Keap1 axis plays a complex role in viral susceptibility, virus-associated inflammation and immune regulation in host cells. However, whether or how the Nrf2/Keap1 axis is involved in the interactions between equine lentiviruses and their hosts remains unclear. Here, we demonstrate that the Nrf2/Keap1 axis was activated during EIAV infection. Mechanistically, EIAV-Rev competitively binds to Keap1 and releases Nrf2 from Keap1-mediated repression, leading to the accumulation of Nrf2 in the nucleus and promoting Nrf2 responsive genes transcription. Subsequently, we demonstrated that the Nrf2/Keap1 axis represses EIAV replication via two independent molecular mechanisms: directly increasing antioxidant enzymes to promote effective cellular resistance against EIAV infection, and repression of Rev-mediated RNA transport through direct interaction between Keap1 and Rev. Together, these data suggest that activation of the Nrf2/Keap1 axis mediates a passive defensive response to combat EIAV infection. The Nrf2/Keap1 axis could be a potential target for developing strategies for combating EIAV infection.
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Antivirais/farmacologia , Produtos do Gene rev/metabolismo , Vírus da Anemia Infecciosa Equina/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Antioxidantes/metabolismo , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. METHODS: Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. RESULTS: A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022-3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259-4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184-3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519-4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. CONCLUSIONS: NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Hepatectomia , Humanos , Colangiocarcinoma/cirurgia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Idoso , Curva ROC , Estudos Retrospectivos , Estimativa de Kaplan-Meier , Adulto , Fatores de RiscoRESUMO
BACKGROUND: In China, both percutaneous microwave/radiofrequency ablation liver partition plus portal vein embolization (PALPP) and transarterial chemoembolization (TACE) plus portal vein embolization (PVE) have been utilized in planned hepatectomy. However, there is a lack of comparative studies on the effectiveness of these two techniques for cases with insufficient future liver remnant (FLR). METHODS: Patients were categorized into either the PALPP group or the TACE + PVE group. Clinical data, including FLR growth rate, complications, secondary resection rate, and overall survival rate, were compared and analyzed for both groups retrospectively. RESULTS: Between December 2014 and October 2021, a total of 29 patients underwent TACE + PVE (n = 12) and PALPP (n = 17). In the TACE + PVE group, 7 patients successfully underwent two-stage hepatectomy, while in the PALPP group, 13 patients underwent the procedure (two-stage resection rate: 58.3% vs. 76.5%, P = 0.42). There were no significant differences in postoperative complications of one-stage procedures (11.8% vs. 8.3%, P > 0.05) and second-stage resection complication (0% vs. 46.2%, P = 0.05) between the TACE + PVE and PALPP groups. However, the PALPP group demonstrated a shorter time to FLR volume growth for second-stage resection (18.5 days vs. 66 days, P = 0.001) and KGR (58.5 ml/week vs. 7.7 ml/week, P = 0.001). CONCLUSIONS: Compared with TACE + PVE, PALPP results in a more significant increase in FLR volume and a higher rate of two-stage resection without increasing postoperative complications.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Hepatectomia , Neoplasias Hepáticas , Micro-Ondas , Veia Porta , Ablação por Radiofrequência , Humanos , Hepatectomia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/cirurgia , Quimioembolização Terapêutica/métodos , Ablação por Radiofrequência/métodos , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/cirurgia , Idoso , Adulto , Fígado/cirurgia , Fígado/irrigação sanguínea , Embolização Terapêutica/métodos , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Taxa de Sobrevida , China/epidemiologia , Terapia CombinadaRESUMO
OBJECTIVE: Immune checkpoint inhibitors (ICIs), specifically targeting the programmed cell death protein-1 or its ligand (PD-1/PD-L1), have been extensively used in the treatment of a spectrum of malignancies, although the predictive biomarkers remain to be elucidated. This study aims to investigate the association between baseline circulating levels of cytokines and the creatinine/cystatin C ratio (CCR) with the treatment outcomes of ICIs in patients with advanced cancer. METHODS: The pre-treatment circulating levels of 10 cytokines (PD-L1, CTLA4, CXCL10, LAG3, HGF, CCL2, MIG, GRANB, IL-18, and IL-6) were measured via automated capillary-based immunoassay platform in the serum of 65 advanced cancer patients treated with anti-PD-1/PD-L1-based systemic therapy and 10 healthy volunteers. The levels of cytokines and CCR were quantified and categorized into high and low groups based on the median value. The associations of serum cytokines and CCR with response to treatment, survival, and immune-related adverse events were assessed. RESULTS: Elevated circulating levels of 6 cytokines (PD-L1, CXCL10, HGF, CCL2, MIG, and IL-6) were observed in cancer patients compared with that in healthy volunteers. The correlation coefficients between cytokines, CCR and nutritional risk index were also calculated. In the cancer cohort (N = 65), low circulating HGF (P = 0.023, P = 0.029), low IL-6 (P = 0.002, P < 0.001), and high CCR (P = 0.031, P = 0.008) were associated with significantly improved progression-free survival (PFS) and overall survival (OS). Multi-variable COX analyses adjusted for clinicopathological factors revealed that low HGF, low IL-6, and high CCR were independent favorable prognostic factors for PFS (P = 0.028, P = 0.010, and P = 0.015, respectively) and OS (P = 0.043, P = 0.003, and P = 0.026, respectively). Grade 2 irAEs occurred more frequently in patients with low levels of circulating CCL2 and LAG3. CONCLUSIONS: Pre-treatment circulating levels of serum IL-6, HGF, and CCR may serve as independent predictive and prognostic biomarkers in advanced cancer patients treated with ICIs-based systemic therapy. These findings might help to identify potential patients who would benefit from these therapies.
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Biomarcadores Tumorais , Creatinina , Citocinas , Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Masculino , Feminino , Neoplasias/tratamento farmacológico , Neoplasias/sangue , Pessoa de Meia-Idade , Idoso , Citocinas/sangue , Prognóstico , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Creatinina/sangue , Biomarcadores Tumorais/sangue , Adulto , Idoso de 80 Anos ou mais , Antígeno B7-H1/sangue , Estudos de Casos e ControlesRESUMO
Equine infectious anemia (EIA) is a contagious disease of horses caused by the equine infectious anemia virus (EIAV). The clinical signs at the acute phase include intermittent high fever, thrombocytopenia, hemorrhage, edema, and anemia. The clinical signs at chronic and relapsing subclinical levels include emaciation and progressive weakness. Surviving horses become lifelong carriers because of the integration of the viral genome into that of the host, and these horses can produce and transmit the virus to other animals. This increases the difficulty of imposing practical control measures to prevent epidemics of this disease. Serological tests measuring the antibodies in equine sera are considered to be a reliable tool for the long-term monitoring of EIA. However, the standard serological tests for EIV either have low sensitivity (e.g., agar gel immunodiffusion test, AGID) or are time consuming to perform (e.g., ELISA and western blotting). The development of a rapid and simple method for detecting the disease is therefore critical to control the spread of EIA. In this study, we designed and developed a colloidal gold immunochromatographic (GICG) test strip to detect antibodies against EIAV based on the double-antigen sandwich. Both the p26 and gp45 proteins were used as the capture antigens, which may help to improve the positive detection rate of the strip. We found that the sensitivity of the test strip was 8 to 16 times higher than those of two commercially available ELISA tests and 128 to 256 times higher than AGID, but 8 to 16 times lower than that of western blotting. The strip has good specificity and stability. When serum samples from experimental horses immunized with the attenuated EIAV vaccine (n = 31) were tested, the results of the test strip showed 100% coincidence with those from NECVB-cELISA and 70.97% with AGID. When testing clinical serum samples (n = 1014), the test strip surprisingly provided greater sensitivity and a higher number of "true positive" results than other techniques. Therefore, we believe that the GICG test strip has demonstrated great potential in the field trials as a simple and effective tool for the detection of antibodies against EIAV. KEY POINTS: ⢠A colloidal gold immunochromatographic (GICG) fast test strip was developed with good specificity, sensitivity, stability, and repeatability ⢠The test strip can be used in point-of-care testing for the primary screening of EIAV antibodies ⢠Both the p26 and gp45 proteins were used as the capture antigens, giving a high positive detection rate in the testing of experimentally infected animal and field samples.
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Vírus da Anemia Infecciosa Equina , Animais , Cavalos , Anticorpos Antivirais , Ensaio de Imunoadsorção Enzimática , Western Blotting , Coloide de OuroRESUMO
OBJECTIVE: To analyze the interrelation between radiation dose and radiation-induced nasopharyngeal ulcer (RINU) in locoregional recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). METHODS: Clinical data were collected from 363 patients with locoregional recurrent NPC who received re-irradiated with definitive IMRT from 2009 to 2017. Twenty-nine patients were diagnosed with RINU. Univariate and multivariate analyses were used to re-evaluate the first and second radiotherapy plans and to identify predictive dosimetric factors. RESULTS: All dosimetric parameters were notably associated with the progression to RINU (p < 0.01) using paired samples Wilcoxon signed rank tests. Multivariate analysis showed that EQD2_ [Formula: see text]D80 (dose for 80 percent volume of the unilateral nasopharynx lesion) was an independent prognostic factor for RINU (p = 0.001). The area under the ROC curve for EQD2_ [Formula: see text]D80 was 0.846 (p < 0.001), and the cutoff point of 137.035 Gy could potentially be the dose tolerance of the nasopharyngeal mucosa. CONCLUSIONS: The sum of equivalent dose in 2 Gy fractions (EQD2) in the overlapping volumes between initial and re-irradiated nasopharyngeal mucosal tissue can be effective in predicting the hazard of developing RINU in NPC patients undergoing radical reirradiation with IMRT and we propose a EQD2_ [Formula: see text]D80 threshold of 137.035 Gy for the nasopharynx.
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Neoplasias Nasofaríngeas , Lesões por Radiação , Radiodermite , Radioterapia de Intensidade Modulada , Reirradiação , Humanos , Carcinoma Nasofaríngeo/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Neoplasias Nasofaríngeas/patologia , Úlcera/etiologia , Dosagem Radioterapêutica , Lesões por Radiação/etiologia , Estudos Retrospectivos , Nasofaringe/patologia , Radiodermite/etiologiaRESUMO
BACKGROUND & AIMS: Complications after laparoscopic liver resection (LLR) are important factors affecting the prognosis of patients, especially for complex hepatobiliary diseases. The present study aimed to evaluate the value of a three-dimensional (3D) printed dry-laboratory model in the precise planning of LLR for complex hepatobiliary diseases. METHODS: Patients with complex hepatobiliary diseases who underwent LLR were preoperatively enrolled, and divided into two groups according to whether using a 3D-printed dry-laboratory model (3D vs. control group). Clinical variables were assessed and complications were graded by the Clavien-Dindo classification. The Comprehensive Complication Index (CCI) scores were calculated and compared for each patient. Multivariable analysis was performed to determine the risk factors of postoperative complications. RESULTS: Sixty-two patients with complex hepatobiliary diseases underwent the precise planning of LLR. Among them, thirty-one patients acquired the guidance of a 3D-printed dry-laboratory model, and others were only guided by traditional enhanced CT or MRI. The results showed no significant differences between the two groups in baseline characters. However, compared to the control group, the 3D group had a lower incidence of intraoperative blood loss, as well as postoperative 30-day and major complications, especially bile leakage (all P < 0.05). The median score on the CCI was 20.9 (range 8.7-51.8) in the control group and 8.7 (range 8.7-43.4) in the 3D group (mean difference, -12.2, P = 0.004). Multivariable analysis showed the 3D model was an independent protective factor in decreasing postoperative complications. Subgroup analysis also showed that a 3D model could decrease postoperative complications, especially for bile leakage in patients with intrahepatic cholelithiasis. CONCLUSION: The 3D-printed models can help reduce postoperative complications. The 3D-printed models should be recommended for patients with complex hepatobiliary diseases undergoing precise planning LLR.
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Laparoscopia , Hepatopatias , Complicações Pós-Operatórias , Impressão Tridimensional , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Hepatopatias/cirurgia , Idoso , Doenças Biliares/prevenção & controle , Doenças Biliares/cirurgia , Doenças Biliares/etiologia , Hepatectomia/métodos , Hepatectomia/efeitos adversos , Adulto , Estudos Retrospectivos , Estudos de CoortesRESUMO
Bottom-up synthesized graphene nanoribbons (GNRs) are increasingly attracting interest due to their atomically controlled structure and customizable physical properties. In recent years, a range of GNR-based field-effect transistors (FETs) has been fabricated, with several demonstrating quantum-dot (QD) behavior at cryogenic temperatures. However, understanding the relationship between the cryogenic charge-transport characteristics and the number of the GNRs in the device is challenging, as the length and location of the GNRs in the junction are not precisely controlled. Here, we present a methodology based on a dual-gate FET that allows us to identify different scenarios, such as single GNRs, double or multiple GNRs in parallel, and a single GNR interacting with charge traps. Our dual-gate FET architecture therefore offers a quantitative approach for comprehending charge transport in atomically precise GNRs.
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BACKGROUND: Postoperative complications are vital factors affecting the prognosis of patients with hepatocellular carcinoma (HCC), especially for complex hepatectomy. The present study aimed to compare perioperative complications between laparoscopic and robotic complex hepatectomy (LCH vs. RCH). METHODS: Patients with solitary HCC after complex hepatectomy were collected from a multicenter database. Propensity score-matched (PSM) analysis was adopted to control confounding bias. Multivariable analysis was performed to determine the prognostic factors. RESULTS: 436 patients were included. After PSM, 43 patients were included in both the LCH and RCH groups. The results showed that compared to LCH, RCH had lower rates of blood loss and transfusion, and lower postoperative 30-day and major morbidity, and post-hepatectomy liver failure (PHLF) (all P < 0.05). Additionally, the length of hospital stay was shorter in the RCH group (P = 0.026). Multivariable analysis showed RCH is an independent protective factor for reducing the 30-day morbidity, major morbidity and PHLF. CONCLUSION: RCH has advantages over LCH in the minimally invasive treatment of complex HCC, as it can reduce the incidence of postoperative morbidity. Therefore, RCH should be considered for patients with HCC who require complex hepatectomy.
Assuntos
Carcinoma Hepatocelular , Hepatectomia , Laparoscopia , Neoplasias Hepáticas , Complicações Pós-Operatórias , Pontuação de Propensão , Procedimentos Cirúrgicos Robóticos , Humanos , Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Masculino , Laparoscopia/efeitos adversos , Feminino , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Idoso , Bases de Dados Factuais , Tempo de Internação , Fatores de Risco , Fatores de Tempo , Medição de Risco , AdultoRESUMO
Exosomes are recognized as noteworthy biomarkers playing unprecedented roles in intercellular communication and disease diagnosis and treatment. It is a prerequisite to obtain high-purity exosomes for the comprehension of exosome biochemistry and further illustration of their functionality/mechanisms. However, the isolation of nanoscale exosomes from endogenous proteins is particularly challenging for small-volume biological samples. Herein, a Dean-flow-coupled elasto-inertial microfluidic chip (DEIC) was developed. It consists of a spiral microchannel with dimensional confined concave structures and facilitates elasto-inertial separation of exosomes with lower protein contaminants from cell culture medium and human serum. The presence of 0.15% (w/v) poly-(oxyethylene) controls the elastic lift force acting on suspended nanoscale particles and makes it feasible for field-free purification of integrity exosomes with a 70.6% recovery and a 91.4% removal rate for proteins. As a proof of concept, the technique demonstrated the individual-vesicle-level biomarker (EpCAM and PD-L1) profiling in combination with simultaneous aptamer-mediated analysis to disclose the sensibility for immune response. Overall, DEIC enables the collection of high-purity exosomes and exhibits potential in integration with downstream analyses of exosomes.
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Exossomos , Humanos , Exossomos/química , Microfluídica/métodos , Técnicas de Cultura de Células , Proteínas/análiseRESUMO
Na3 V2 (PO4 )2 O2 F (NVPOF) is widely accepted as advanced cathode material for sodium-ion batteries with high application prospects ascribing to its considerable specific capacity and high working voltage. However, challenges in the full realization of its theoretical potential lie in the novel structural design to accelerate its Na+ diffusivity. Herein, considering the important role of polyanion groups in constituting Na+ diffusion tunnels, boron (B) is doped at the P-site to obtain Na3 V2 (P2- x Bx O8 )O2 F (NVP2- x Bx OF). As evidenced by density functional theory modeling, B-doping induces a dramatic decrease in the bandgap. Delocalization of electrons on the O anions in BO4 tetrahedra is observed in NVP2- x Bx OF, which dramatically lowers the electrostatic resistance experienced by Na+ . As a result, the Na+ diffusivity in the NVP2- x Bx OF cathode has accelerated up to 11 times higher, which secures a high rate property (67.2 mAh g-1 at 60 C) and long cycle stability (95.9% capacity retention at 108.6 mAh g-1 at 10 C after 1000 cycles). The assembled NVP1.90 B0.10 OF//Se-C full cell demonstrates exceptional power/energy density (213.3 W kg-1 @ 426.4 Wh kg-1 and 17970 W kg-1 @ 119.8 Wh kg-1 ) and outstanding capability to withstand long cycles (90.1% capacity retention after 1000 cycles at 105.3 mAh g-1 at 10 C).
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Salmonella enterica subsp. enterica serovar Abortusequi is a major pathogen in horse and donkey herds, causing abortion in pregnant equids and resulting in enormous economic losses. A rapid and reliable method is urgently needed to detect S. Abortusequi in herds where the disease is suspected. To achieve this goal, a TaqMan-based real-time PCR assay targeting the gene for the flagellin protein phase 2 antigen FljB was developed. This real-time PCR assay had high specificity, sensitivity, and reproducibility. The detection limit of the assay was 30 copies/µL of standard plasmid and 10 CFU/µL of bacterial DNA. Furthermore, 540 clinical samples, including 162 tissue, 192 plasma, and 186 vaginal swab samples collected between 2018 and 2021 in China, were tested to assess the performance of the developed assay. Compared to the gold standard method of bacterial isolation, the real-time PCR assay exhibited 100% positive agreement for all tissue, plasma and vaginal swab tests. Additionally, this assay detected DNA from S. Abortusequi from 56.7% (34/60) culture-negative tissue and 22.9% (41/179) culture-negative vaginal swab samples from infected equids. Receiver operating characteristic analysis demonstrated that the results of the developed real-time PCR assays were in significant agreement with those of the culture method. The real-time PCR assay can be completed within 45 min of extraction of DNA from samples. Our results show that this assay could serve as a reliable tool for the rapid detection of S. Abortusequi in tissue, plasma, and vaginal swab clinical samples.
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Salmonelose Animal , Salmonella enterica , Gravidez , Feminino , Animais , Cavalos/genética , Salmonella enterica/genética , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Salmonelose Animal/diagnóstico , Salmonelose Animal/microbiologia , Salmonella/genética , DNA Bacteriano/genética , Sensibilidade e EspecificidadeRESUMO
Equine infectious anemia virus (EIAV) and HIV are both members of the Lentivirus genus and are similar in major virological characters. EIAV endangers the horse industry. In addition, EIAV can also be used as a model for HIV research. The maturation of the lentiviral Env protein, which is necessary for viral entry, requires Env to be folded in the endoplasmic reticulum (ER). It is currently unclear how this process is regulated. Mitochondrion-associated endoplasmic reticulum membrane (MAM) is a specialized part of the close connection between the ER and mitochondria, and one of the main functions of MAM is to promote oxidative protein production in the ER. SYNJ2BP is one of the key proteins that make up the MAM, and we found that SYNJ2BP is essential for EIAV replication. We therefore constructed a SYNJ2BP knockout HEK293T cell line in which the number of MAMs is significantly reduced. Moreover, overexpression of SYNJ2BP could increase the number of MAMs. Our study demonstrates that SYNJ2BP can improve the infectivity of the EIAV virus with elevated production of the viral Env protein through increased MAM formation. Interestingly, SYNJ2BP was able to improve the production of not only EIAV Env but also HIV. Further investigation showed that MAMs can provide more ATP and calcium ions, which are essential factors for Env production, to the ER and can also reduce ER stress induced by HIV or EIAV Envs to increase the Env production level in cells. These results may help us to understand the key production mechanisms of lentiviral Env. IMPORTANCE Lentiviral Env proteins, which are rich in disulfide bonds, need to be fully folded in the ER; otherwise, misfolded Env proteins will induce ER stress and be degraded by ER-associated protein degradation (ERAD). To date, it is still unclear about Env production mechanism in the ER. MAM is the structure of closely connection between the ER and mitochondria. MAMs play important roles in the calcium steady state and oxidative stress, especially in the production of oxidative protein. For the first time, we found that SYNJ2BP can promote the production of lentiviral Env proteins by providing the ATP and calcium ions required for oxidative protein production in the ER and by reducing ER stress through facilitating formation of MAMs. These studies shed light on how MAMs improve lentiviral Env production, which will lay the foundation for the study of replication mechanisms in other lentiviruses from the perspective of the cellular organelle microenvironment.
Assuntos
Infecções por HIV , Vírus da Anemia Infecciosa Equina , Cavalos , Humanos , Animais , Produtos do Gene env/metabolismo , Cálcio/metabolismo , Células HEK293 , Vírus da Anemia Infecciosa Equina/genética , Vírus da Anemia Infecciosa Equina/metabolismo , Retículo Endoplasmático/metabolismo , Mitocôndrias/metabolismo , Infecções por HIV/metabolismo , Trifosfato de Adenosina/metabolismo , Dissulfetos/metabolismo , Proteínas de Membrana/metabolismoRESUMO
Quantum illumination is a quantum optical sensing technique, which employs an entangled source to detect low-reflectivity object immersed in a bright thermal background. Hybrid cavity-optomagnonics system promises to work as quantum illumination because a yttrium iron garnet (YIG) sphere can couple to microwave field and optical field. In this paper, we propose a scheme to enhance the entanglement between the output fields of the microwave and optical cavities by considering the intrinsic Kerr nonlinearity of the YIG. We investigate the difference between intrinsic Kerr nonlinearity and optomagnonical parametric-type coupling on improving entanglement. Our result show that the large value optomagnonical parametric-type coupling does not mean the large entanglement, nevertheless, the large value of Kerr nonlinearity does monotonously improve the entanglement for our group of parameters. Consequently, under feasible parameters of current experiment, the signal-to-noise ratio and probability of detection error can be improved after considering the magnon Kerr nonlinearity.
RESUMO
We demonstrate 112 orbital angular momentum (OAM) modes amplification based on a designed and fabricated 7-ring-core erbium-doped fiber (7RC-EDF). The differential mode gain (DMG) of all the intra-core OAM modes in 7RC-EDF is effectively reduced. The DMG of intra-core modes can be suppressed by the high overlap between the signal modes and pump fundamental mode resulting from the designed structures of the ring core assisted by a trench. The differential gain of the inter-core can be controlled by the power of the core-pump configuration as well. With an experimentally optimized scheme of the pump power of each core, a record low-DMG of 2.8 dB among the 112 OAM modes (16-OAM-mode per core in the 7-core) is achieved at a wavelength of 1550 nm. The obtained favorable performance of the 112 OAM modes based on 7RC-EDF indicates it may promote a long-haul high-density OAM modes multiplexed transmission.
RESUMO
In this work, Ti3 Al1-x Six C2 (x=0, 0.2, 0.4, and 0.6) with Al/Si solid solution structure are synthesized, and the effects of Si on their oxidation behaviors at 1000 °C are evaluated. The addition of Si not only contributes to the formation of Ti5 Si3 impurity but also affects the composition of the oxide scale. Particularly, the incorporation of Si in the TiO2 lattice is demonstrated, which alters the formation energy of the (110) plane in TiO2 , thus leading to the preferential growth of Si-doped TiO2 to dendritic congeries. Moreover, the Si addition is believed to affect mass transportation during the oxidation process, which accelerates the formation of a continuous Al2 O3 layer in the oxide scale. With an optimized Si content, the oxidation of Ti3 Al1-x Six C2 is restrained. However, with excess Si content, the continuity of the resulting Al2 O3 layer is destroyed, thus the oxidation rate rises again.
RESUMO
Equine infectious anemia (EIA) is an important viral disease characterized by persistent infection in equids worldwide. Most EIA cases are life-long virus carriers with low antibody reactions and without the appearance of clinical symptoms. A serological test with high sensitivity and specificity is required to detect inapparent infection. In this study, a B-cell common epitope-based blocking ELISA (bELISA) was developed using a monoclonal antibody together with the EIAV p26 protein labelled with HRP. The test has been evaluated against the standard and with field serum samples globally. This bELISA test can be completed within 75 min, and the sensitivity is higher than those of either the AGID or one commercial cELISA kit. This bELISA assay was 8-16 times more analytically sensitive than AGID, and 2 to 4 times more analytically sensitive than one cELISA kit by testing three sera from the USA, Argentina, and China, respectively. The 353 serum samples from Argentina were tested, in comparison with AGID, the diagnostic sensitivity and specificity of our bELISA assay were 100% (154/154) and 97.0% (193/199), respectively, and the accuracy of the bELISA test was 98.3%. The bELISA test developed in this study is a rapid, sensitive, specific method for the detection of EIAV infection, and could be a promising candidate for use in the monitoring of the EIA epidemic worldwide. KEY POINTS: ⢠A universal epitope-based blocking enzyme-linked immunosorbent assay (bELISA) was developed for detection of antibodies to EIAV. ⢠The bELISA assay can be used to test EIAV serum samples from different regions of the world including North America, South America, Europe, and Asia. ⢠The bELISA assay was evaluated in three different international labs and showed a better performance than other commercial kits.