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IMPORTANCE: Porcine epidemic diarrhea (PED) caused by PED virus (PEDV) remains a big threat to the swine industry worldwide. Vaccination with live attenuated vaccine is a promising method to prevent and control PED, because it can elicit a more protective immunity than the killed vaccine, subunit vaccine, and so on. In this study, we found two obvious deletions in the genome of a high passage of AH2012/12. We further confirmed the second deletion which contains seven amino acids at the carboxy-terminus of the S2 gene and the start codon of ORF3 can reduce its pathogenicity in vivo. Animal experiments indicated that the recombinant PEDV with deleted carboxy-terminus of S gene showed higher IgG, IgA, neutralization antibodies, and protection effects against virus challenge than the killed vaccine. These data reveal that the engineering of the carboxy-terminus of the S2 gene may be a promising method to develop live attenuated vaccine candidates of PEDV.
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Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Animais , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Diarreia , Vírus da Diarreia Epidêmica Suína/genética , Vírus da Diarreia Epidêmica Suína/patogenicidade , Suínos , Doenças dos Suínos/virologia , Vacinas Atenuadas/genética , Vacinas de Produtos Inativados , Vacinas Virais/genética , VirulênciaRESUMO
Due to the suitable bandgap structure, efficient conversion rates of photon to electron, adjustable optical bandgap, high electron mobility/aspect ratio, low defects, and outstanding optical and electrical properties for device design, III-V semiconductors have shown excellent properties for optoelectronic applications, including photodiodes, photodetectors, solar cells, photocatalysis, etc. In particular, III-V nanostructures have attracted considerable interest as a promising photodetector platform, where high-performance photodetectors can be achieved based on the geometry-related light absorption and carrier transport properties of III-V materials. However, the detection ranges from Ultraviolet to Terahertz including broadband photodetectors of III-V semiconductors still have not been more broadly development despite significant efforts to obtain the high performance of III-V semiconductors. Therefore, the recent development of III-V photodetectors in a broad detection range from Ultraviolet to Terahertz, and future requirements are highly desired. In this review, the recent development of photodetectors based on III-V semiconductor with different detection range is discussed. First, the bandgap of III-V materials and synthesis methods of III-V nanostructures are explored, subsequently, the detection mechanism and key figures-of-merit for the photodetectors are introduced, and then the device performance and emerging applications of photodetectors are provided. Lastly, the challenges and future research directions of III-V materials for photodetectors are presented.
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OBJECTIVE: We aimed to investigate the prognostic factors of pediatric extracorporeal cardiopulmonary resuscitation (ECPR). METHODS: The retrospective study included a total of 77 pediatric cases (7 neonates and 70 children) who underwent ECPR after in-hospital and out-of-hospital cardiac arrest between July 2007 and December 2022. Primary endpoints were complications, while secondary endpoints included all-cause in-hospital mortality. RESULTS: Among the 45 cases experiencing complications, 4 neonates and 41 children had multiple simultaneous complications, primarily neurological issues in 25 cases. Additionally, organ failure occurred in 11 cases, and immunodeficiency was present in two cases. Furthermore, 9 cases experienced bleeding events, and 13 cases showed thrombosis. Patients with complications had lower weight, shorter ECMO durations, and longer CPR durations. Non-survivors had longer CPR durations and shorter durations of ECMO, ICU stay, and mechanical ventilation compared to survivors. Complications were more prevalent in non-survivors, particularly organ failure and bleeding events. CONCLUSION: Weight, CPR duration, and ECMO duration were associated with complications, suggesting areas for treatment optimization. The higher occurrence of complications in non-survivors underscores the importance of early detection and management to improve survival rates. Our findings suggest clinicians consider these factors in prognostic assessments to enhance the effectiveness of ECPR programs.
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Reanimação Cardiopulmonar , Oxigenação por Membrana Extracorpórea , Mortalidade Hospitalar , Humanos , Estudos Retrospectivos , Masculino , Feminino , Oxigenação por Membrana Extracorpórea/métodos , Lactente , China/epidemiologia , Pré-Escolar , Reanimação Cardiopulmonar/métodos , Recém-Nascido , Criança , Parada Cardíaca/terapia , Parada Cardíaca/mortalidade , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/mortalidade , AdolescenteRESUMO
A special data processing method for the terahertz frequency domain reflection spectroscopy system has been proposed to analyze the characteristics of a polar mixed liquid. This novel and practical measurement system is characterized by a simpler optical structure and a tunable output frequency range of 0.1-1 THz. By Hilbert transform, stationary wavelet transform, and time domain zero setting method, the reflection coefficient that has been eliminated by the noise and the Fabry-Pérot effect can be obtained by the self-reference calibration method. Then, the dielectric function of the ethanol/n-hexane and propanol/n-hexane mixtures with different mixture ratios can be extracted by this method. In addition, a significant deviation can be observed between the imaginary part of the measured dielectric function and the ideal calculated value. These results indicate that during the mixing process of polar and nonpolar liquids, the hydroxyl functional groups of alcohols significantly change the molecular arrangement pattern of the mixture. The arrangement pattern will result in the formation of the new permanent dipole moment. This study lays a solid foundation for future research on the microscopic mechanism of intermolecular interaction using terahertz frequency domain reflection spectroscopy.
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BACKGROUND: In patients undergoing mechanical thrombectomy (MT), adjunctive antithrombotic might improve angiographic reperfusion, reduce the risk of distal emboli and reocclusion but possibly expose patients to a higher intracranial hemorrhage risk. This study evaluated the safety and efficacy of combined MT plus eptifibatide for acute ischemic stroke. METHODS: This was a propensity-matched analysis of data from 2 prospective trials in Chinese populations: the ANGEL-ACT trial (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke) in 111 hospitals between November 2017 and March 2019, and the EPOCH trial (Eptifibatide in Endovascular Treatment of Acute Ischemic Stroke) in 15 hospitals between April 2019 and March 2020. The primary efficacy outcome was good outcome (modified Rankin Scale score 0-2) at 3 months. Secondary efficacy outcomes included the distribution of 3-month modified Rankin Scale scores and poor outcome (modified Rankin Scale score 5-6) and successful recanalization. The safety outcomes included any intracranial hemorrhage, symptomatic intracranial hemorrhage, and 3-month mortality. Mixed-effects logistic regression models were used to account for within-hospital clustering in adjusted analyses. RESULTS: Eighty-one combination arm EPOCH subjects were matched with 81 ANGEL-ACT noneptifibatide patients. Compared with the no eptifibatide group, the eptifibatide group had significantly higher rates of successful recanalization (91.3% versus 81.5%; P=0.043) and 3-month good outcomes (53.1% versus 33.3%; P=0.016). No significant difference was found in the remaining outcome measures between the 2 groups. All outcome measures of propensity score matching were consistent with mixed-effects logistic regression models in the total population. CONCLUSIONS: This matched-control study demonstrated that MT combined with eptifibatide did not raise major safety concerns and showed a trend of better efficacy outcomes compared with MT alone. Overall, eptifibatide shows potential as a periprocedural adjunctive antithrombotic therapy when combined with MT. Further randomized controlled trials of MT plus eptifibatide should be prioritized. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03844594 (EPOCH), NCT03370939 (ANGEL-ACT).
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/cirurgia , Eptifibatida , Humanos , Hemorragias Intracranianas/etiologia , Estudos Prospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Resultado do TratamentoRESUMO
A new slot-based antenna design capable of producing horizontal polarization for unmanned aerial vehicle (UAV) ground control station (GCS) applications is outlined in this paper. The proposed antenna consists of oversize coaxial cylinders, slots, and slot-feed assembly. Each of the four vertical slots, arranged periodically around the antenna's outer cylinder, emits a horizontally polarized broad beam of radiation, in phase, to produce an omnidirectional pattern. The antenna possesses a low-ripple ±0.5 dB in azimuth gain (yaw) due to its symmetric axis shape and an enclosed feed within itself, which does not radiate and interfere with the main azimuth pattern. This is crucial for a UAV GCS to symmetrically extend its coverage range in all directions against yaw planes. Simulation and measurement results reveal that the antenna maintains stable gain in the omnidirectional pattern (+0.5 dB) over the entire operational frequency band (2.55 GHz to 2.80 GHz), where S11 is lower than -10 dB. A further advantage of this configuration is its enhanced polarization purity of -40 dB over the full frequency band. The direct-current (DC) grounding approach used in this antenna is beneficial due to its electrostatic discharge (ESD) and lightning protection. Furthermore, its aerodynamic, self-supporting, and surface-mount structural shape makes this antenna a good and worthy choice for a UAV GCS.
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BACKGROUND: The aim of this study was to analyze and summarize the clinical characteristics of elderly patients with coronavirus disease 2019 (COVID-19) and compare the differences of young-old patients (60-74 years old) and old-old patients (≥75 years old). METHODS: In thisretrospective, multicenter study, the medical records of elderly patients who were diagnosed with COVID-19 in Hunan province, China, from January 21 to February 19, 2020 were reviewed. The characteristics of young-old patients and old-old patients were compared. RESULTS: Of the 105 elderly patientsconfirmed withCOVID-19, 81.0% were young-old patients, and 19.0% were old-old patients; 54.3% of elderly patients were females. Overall, 69.5% of elderly patients had underlying diseases, and the most common comorbidities included hypertension (43.8%), diabetes (25.7%), and cardiac disease (16.2%). Of the elderly patients, 22.9% were severe and 10.5% were critical severe cases. On admission, the most frequent symptoms in elderly patients included fever (66.7%), cough (64.8%), and fatigue (33.3%). Lymphopenia (31.4%), increased D-dimer (38.1%), depressed albumin (36.2%), elevated lactate dehydrogenase (41.0%), and a high level of C-reactive protein (79.0%) were common among elderly patients with COVID-19. The median prothrombin time (PT) and the activated partial thromboplastin time (APTT) were longer in old-old patients than young-old patients (PT median 12.3 vs. 13.1 s, p = 0.007; APTT median 39.0 vs. 33.5 s, p = 0.045). Young-old patients showed fewer complications (14.1%) than old-old patients (40.0%; p = 0.0014) and fewer received invasive ventilator support (3.5 vs. 25.0%, p = 0.006). As of March 11, 2020, 85.7% of elderly patients had been discharged, 3 deaths had occurred, and 11.4% were still hospitalized. CONCLUSIONS: Elderly patients usually have chronic medical illness and are likely to have a severe or critically severe condition. They could show atypical symptoms without fever or cough and multiple organ dysfunction. Old-old patients tend to have more complications than young-old patients during hospitalization. Careful nursing, observation, and systemic treatment are very important in elderly patients.
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Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Contagem de Células Sanguíneas , COVID-19 , China , Infecções por Coronavirus/epidemiologia , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Tempo de Tromboplastina Parcial , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , SARS-CoV-2 , Avaliação de SintomasRESUMO
This paper presents a new shape (s-shape monopole) of a super wideband antenna using stepped meander lines, a quarter waveguide transformer feeding line, and a defected ground structure (DGS). The antenna will be used for multiple wireless communication applications like WIMAX/WLAN/ISM/UWB, and also for several wireless communication applications. The total dimensions of the proposed antenna are 35 mm × 35 mm × 1.57 mm or 0.36 λo × 0.36 λo × 0.016 λo, which are the corresponding electrical dimensions with free-space wavelength (λo) at the lower operating frequency. The antenna is designed and simulated into two steps: the first (Antenna 1) covers a bandwidth of 18.2 GHz, while the second (Antenna 2, using DGS) covers a super wide bandwidth of 37.82 GHz (3.08-40.9 GHz). The measured fractional bandwidth and bandwidth ratio of the antenna are 174.68% and 13.009:1, respectively, which is operating from 3.09-40.2 GHz. The maximum calculated gain and efficiency are 5.9 dBi and 92.7%, respectively. The time-domain performance is good due to the calculation of the system fidelity factor, group delay, and its linear and constant phase variation.
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In this paper, an extremely sensitive microwave sensor is designed based on a complementary symmetric S shaped resonator (CSSSR) to evaluate dielectric characteristics of low-permittivity material. CSSSR is an artificial structure with strong and enhanced electromagnetic fields, which provides high sensitivity and a new degree of freedom in sensing. Electromagnetic simulation elucidates the effect of real relative permittivity, real relative permeability, dielectric and magnetic loss tangents of the material under test (MUT) on the resonance frequency and notch depth of the sensor. Experiments are performed at room temperature using low-permittivity materials to verify the concept. The proposed design provides differential sensitivity between 102% to 95% as the relative permittivity of MUT varies from 2.1 to 3. The percentage error between simulated and measured results is less than 0.5%. The transcendental equation has been established by measuring the change in the resonance frequency of the fabricated sensor due to interaction with the MUT.
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BACKGROUND: Metagenomic next-generation sequencing (mNGS) has made a revolution in the mode of pathogen identification. We decided to explore the diagnostic value of blood and bronchoalveolar lavage fluid (BALF) as mNGS samples in pneumonia. METHODS: We retrospectively reviewed 467 mNGS results and assessed the diagnostic performance of paired blood and BALF mNGS in 39 patients with pneumonia. RESULTS: For bacteria and fungi, 16 patients had culture-confirmed pathogen diagnosis, while 13 patients were culture-negative. BALF mNGS was more sensitive than blood mNGS (81.3% vs. 25.0%, p=0.003), and the specificity in BALF and blood mNGS was not statistically significant different (76.9% vs. 84.6%, p=0.317). For 10 patients without culture test, treatments were changed in 2 patients. For viruses, Epstein-Barr virus was positive in blood mNGS in 9 patients. Human adenovirus was detected in both BALF and blood mNGS in 3 patients. CONCLUSION: Our study suggests that BALF mNGS is more sensitive than blood mNGS in detecting bacteria and fungi, but blood also has advantages to identify the pathogens of pneumonia, especially for some viruses.
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Microwave undulators have great potential to be used in short-wavelength free-electron lasers. In this paper, the properties of a corrugated waveguide and its performance as an undulator cavity for a UK X-ray free-electron laser were systematically studied. The equations presented in this paper allow a fast estimation of the dimensions of the corrugated waveguide. An undulator cavity operating at 36â GHz designed for the HE11 and HE12 modes was investigated and the performance of both modes compared.
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Retrospective analysis was performed at an affiliated university children's hospital with consecutive patients receiving a venoarterial extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock from July 2007 to May 2018. Fifty-six patients underwent VA-ECMO for refractory cardiogenic shock with the median age of 39.0 (1.5, 103.5) months were included. Median ECMO duration was 87 h, and the median length of hospital stay was 22 days. Successful ECMO weaning rate was 68%. Thirty-day mortality in this cohort was 39% (22/56), among which the mortality of fulminant myocarditis and postcardiotomy cardiogenic shock (PCS) were 23% (6/26) and 52% (12/23), respectively. Multivariate Cox proportional hazard regression analysis identified prolonged prothrombin time (PT) > 6 s and elevated lactate level 24 h after ECMO initiation were associated with 30-day mortality.Conclusions: Pediatric VA-ECMO for refractory cardiogenic shock appears to be a satisfactory salvage therapy to various fatal diseases in this retrospective study. Prolonged PT > 6 s and elevated lactate level 24 h were significant predictors of 30-day mortality. What is Known: ⢠VA-ECMO is a salvage therapy for refractory cardiogenic shock in pediatrics. What is New: ⢠Prothrombin time > 6 s was a significant predictor of 30-day mortality. ⢠Elevated lactate level 24 h was a significant predictor of 30-day mortality.
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Oxigenação por Membrana Extracorpórea/mortalidade , Mortalidade Hospitalar , Complicações Pós-Operatórias/mortalidade , Choque Cardiogênico/mortalidade , Criança , Pré-Escolar , Oxigenação por Membrana Extracorpórea/métodos , Feminino , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Ácido Láctico/sangue , Tempo de Internação , Masculino , Miocardite/mortalidade , Miocardite/terapia , Complicações Pós-Operatórias/terapia , Modelos de Riscos Proporcionais , Protrombina/metabolismo , Estudos Retrospectivos , Terapia de Salvação/métodos , Terapia de Salvação/mortalidade , Choque Cardiogênico/terapia , Fatores de TempoRESUMO
The objective of this study is to establish reliable markers for mortality in children with refractory cardiogenic shock who underwent extracorporeal membrane oxygenation. A retrospective observational cohort study was performed at academic children's hospital for forty-three consecutive pediatric patients who required veno-arterial extracorporeal membrane oxygenation (ECMO) support with refractory cardiogenic shock from January 2011 to October 2017. 30-day mortality in this cohort was 39.5% (17/43), and successful ECMO weaning rate was 69.8%. Blood lactate was elevated before ECMO implantation and the lactate peak concentration had significant differences between survivors and non-survivors, 8.4 ± 4.3 vs 13.9 ± 6.6 mmol/L. AUC to ROC curve analysis of lactate peak was 0.745 (p < 0.05), and the best cut-off value was 14.2 mmmol/L (sensitivity: 53%, specificity: 92%). The length of lactate level > 5 mmol/L was the most significant connection to 30-day mortality. Its AUC was 0.722 (p < 0.05), and the best cut-off value was 3.3 h (sensitivity: 67%, specificity: 80%). Non-survivors had significantly higher lactate levels during 0-6 h of ECMO support, compared to survivors, which also persisted at 7-12-h, 13-24-h, and 25-48-h ECMO. However, lactate clearance at 12 h, 24 h, 48 h revealed no significant differences between survivors and non-survivors based on 30-day mortality. Lactate peak and the duration of high lactate concentration before ECMO were reliable markers for 30-day mortality of pediatric patients with refractory cardiogenic shock. Static lactate values after ECMO implantation were associated with mortality while dynamic lactate value was not. Ensuring adequate ECMO support after cannulation and early diagnostic and intervention should be implemented to normalize the lactate level.
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Biomarcadores/sangue , Oxigenação por Membrana Extracorpórea/métodos , Ácido Láctico/sangue , Choque Cardiogênico/sangue , Área Sob a Curva , Criança , Pré-Escolar , Estudos de Coortes , Oxigenação por Membrana Extracorpórea/efeitos adversos , Feminino , Mortalidade Hospitalar , Hospitais Pediátricos , Humanos , Lactente , Masculino , Curva ROC , Estudos Retrospectivos , Choque Cardiogênico/mortalidade , Choque Cardiogênico/terapia , Sobreviventes , Resultado do Tratamento , Desmame do Respirador/efeitos adversos , Desmame do Respirador/métodosRESUMO
The paper presents a highly efficient, low cost, ultra-wideband, microstrip monopole antenna for microwave imaging and wireless communications applications. A new structure (z-shape, ultra-wideband (UWB) monopole) is designed, which consists of stepped meander lines to achieve super-wide bandwidth and high efficiency. Three steps are used to design the proposed structure for the purpose to achieve high efficiency and wide bandwidth. The antenna bandwidth is enhanced by varying the length of meander line slots, optimization of the feeding line and with the miniaturization of the ground width. The simulated and measured frequency bands are 2.7-22.5 GHz and 2.8-22.7 GHz (156% fractional bandwidth), respectively. The dimensions of the antenna are 38 mm × 35 mm × 1.57 mm, and its corresponding electrical size is 2.41 λg × 2.22 λg × 0.09 λg, where guided wavelength λg is at the center frequency (12.75 GHz). This antenna achieved a high bandwidth ratio (8.33:1). The realized gain is varying from 1.6-6.4 dBi, while that of efficiency is 70% to 93% for the whole band. Radiation patterns are measured at four operating frequencies. It has an acceptable group delay, fidelity factor, and phase variation results that satisfy the limit of ultra-wideband in the form of the time domain.
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OBJECTIVE: To investigate the effect and mechanism of glucosides of chaenomeles speciosa (GCS) on ischemia/reperfusion-induced brain injury in mouse model. METHODS: Fifty 8-week C57BL/C mice were randomly divided into five groups with 10 in each group:sham group, model group, GCS 30 mg/kg group, GCS 60 mg/kg group and GCS 90 mg/kg group, and the GCS was administrated by gavage (once a day) for 14 d. HE staining was performed to investigate the cell morphology; the Zea-Longa scores were measured for neurological activity; TUNEL staining was performed to investigate the cell apoptosis; ELISA was used to detected the oxidative stress and inflammation; Western Blot was performed to investigate the key pathway and neurological functional molecules. RESULTS: Compared with the sham group, the brain tissues in model group were seriously damaged, presenting severe cell apoptosis, oxidative stress and inflammation, associated with increased NF-κB P65 and TNF-α levels as well as decreased myelin associate glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (OMgp)levels (all P<0.01). Compared with the model group, the brain tissues in GCS groups were ameliorated, and cell apoptosis, oxidative stress and inflammation were inhibited, associated with decreased NF-κB P65 and TNF-α levels as well as increased MAG and OMgp levels (all P<0.01), which were more markedly in GCS 60 mg/kg group. CONCLUSIONS: GCS can inhibit the NF-κB P65 and TNF-α, reduce the oxidative stress and inflammation, decrease the cell apoptosis in mouse ischemia/reperfusion-induced brain injury model, and 60 mg/kg GCS may be the optimal dose.
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Lesões Encefálicas , Glucosídeos , Rosaceae , Fator de Necrose Tumoral alfa , Animais , Encéfalo/efeitos dos fármacos , Lesões Encefálicas/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Distribuição Aleatória , Rosaceae/química , Fator de Necrose Tumoral alfa/genéticaRESUMO
To explore the relationship between the clinical manifestations and functional magnetic resonance images of delayed encephalopathy after carbon monoxide intoxication. Six patients received the MRI were diagnosed with delayed encephalopathy after carbon monoxide (CO) poisoning. Clinical manifestations were observed in each patient. MRI revealed multiple lesions. The majority of the lesions were located in the globus pallidus, sub cortical white matter, and basal ganglia. The cognitive injury, akinetic mutism, fecal and uroclepsia, forced crying, forced laughing and extra pyramidal syndromes such as chorea and parkinsonism were manifested in clinic. Cognitive impairment improved greatly while involuntary movements only improved slightly after several months. Meanwhile brain MRI suggested remarkable improvement. Neuroimaging directly correlated with the clinical manifestations.
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Encefalopatias/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Intoxicação por Monóxido de Carbono/diagnóstico por imagem , Transtornos Cognitivos/diagnóstico por imagem , Cognição , Neuroimagem Funcional/métodos , Imageamento por Ressonância Magnética , Idoso , Encefalopatias/induzido quimicamente , Encefalopatias/fisiopatologia , Encefalopatias/psicologia , Intoxicação por Monóxido de Carbono/complicações , Intoxicação por Monóxido de Carbono/fisiopatologia , Intoxicação por Monóxido de Carbono/psicologia , China , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Discinesia Induzida por Medicamentos/diagnóstico por imagem , Discinesia Induzida por Medicamentos/etiologia , Discinesia Induzida por Medicamentos/fisiopatologia , Discinesia Induzida por Medicamentos/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de TempoRESUMO
Rationale: Autophagy dysregulation is known to be a mechanism of doxorubicin (DOX)-induced cardiotoxicity (DIC). Mitochondrial-Endoplasmic Reticulum Contacts (MERCs) are where autophagy initiates and autophagosomes form. However, the role of MERCs in autophagy dysregulation in DIC remains elusive. FUNDC1 is a tethering protein of MERCs. We aim to investigate the effect of DOX on MERCs in cardiomyocytes and explore whether it is involved in the dysregulated autophagy in DIC. Methods: We employed confocal microscopy and transmission electron microscopy to assess MERCs structure. Autophagic flux was analyzed using the mCherry-EGFP-LC3B fluorescence assay and western blotting for LC3BII. Mitophagy was studied through the mCherry-EGFP-FIS1 fluorescence assay and colocalization analysis between LC3B and mitochondria. A total dose of 18 mg/kg of doxorubicin was administrated in mice to construct a DIC model in vivo. Additionally, we used adeno-associated virus (AAV) to cardiac-specifically overexpress FUNDC1. Cardiac function and remodeling were evaluated by echocardiography and Masson's trichrome staining, respectively. Results: DOX blocked autophagic flux by inhibiting autophagosome biogenesis, which could be attributed to the downregulation of FUNDC1 and disruption of MERCs structures. FUNDC1 overexpression restored the blocked autophagosome biogenesis by maintaining MERCs structure and facilitating ATG5-ATG12/ATG16L1 complex formation without altering mitophagy. Furthermore, FUNDC1 alleviated DOX-induced oxidative stress and cardiomyocytes deaths in an autophagy-dependent manner. Notably, cardiac-specific overexpression of FUNDC1 protected DOX-treated mice against adverse cardiac remodeling and improved cardiac function. Conclusions: In summary, our study identified that FUNDC1-meditated MERCs exerted a cardioprotective effect against DIC by restoring the blocked autophagosome biogenesis. Importantly, this research reveals a novel role of FUNDC1 in enhancing macroautophagy via restoring MERCs structure and autophagosome biogenesis in the DIC model, beyond its previously known regulatory role as an mitophagy receptor.
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Autofagia , Cardiotoxicidade , Doxorrubicina , Retículo Endoplasmático , Proteínas de Membrana , Proteínas Mitocondriais , Miócitos Cardíacos , Animais , Doxorrubicina/efeitos adversos , Doxorrubicina/farmacologia , Camundongos , Autofagia/efeitos dos fármacos , Cardiotoxicidade/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitofagia/efeitos dos fármacos , Masculino , Autofagossomos/metabolismo , Autofagossomos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Modelos Animais de DoençasRESUMO
A novel terahertz polarization isolator using a two-dimensional square lattice tellurium rod array is numerically investigated at the interesting band of 0.22 THz in this short paper. The isolator is designed by inserting six hexagonal tellurium rods into a fully polarized photonic crystals waveguide with high efficiency of -0.34 dB. The TE and TM photonic band gaps of the 7 × 16 tellurium photonic crystals are computed based on the plane wave expansion method, which happen to coincide at the normalized frequency domain from 0.3859(a/λ) to 0.4033(a/λ), corresponding to the frequency domain from 0.2152 to 0.2249 THz. The operating bandwidth of the tellurium photonic crystals waveguide covers 0.2146 to 0.2247 THz, calculated by the finite element method. The six hexagonal tellurium rods with smaller circumradii of 0.16a serve to isolate transverse electric waves and turn a blind eye to transverse magnetic waves. The polarization isolation function and external characteristic curves of the envisaged structure are numerically simulated, which achieves the highest isolation of -33.49 dB at the central frequency of 0.2104 THz and the maximum reflection efficiency of 98.95 percent at the frequency of 0.2141 THz. The designed isolator with a unique function and high performance provides a promising approach for implementing fully polarized THz devices for future 6G communication systems.
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Porcine deltacoronavirus (PDCoV), a cross-species transmissible enterovirus, frequently induces severe diarrhea and vomiting symptoms in piglets, which not only pose a significant menace to the global pig industry but also a potential public safety risk. In a previous study, we isolated a vaccine candidate, PDCoV CZ2020-P100, by passaging a parental PDCoV strain in vitro, exhibiting attenuated virulence and enhanced replication. However, the factors underlying these differences between primary and passaged strains remain unknown. In this study, we present the transcriptional landscapes of porcine kidney epithelial cells (LLC-PK1) cells infected with PDCoV CZ2020-P1 strain and P100 strain using the RNA-sequencing. We identified 105 differentially expressed genes (DEGs) in P1-infected cells and 295 DEGs in P100-infected cells. Enrichment analyses indicated that many DEGs showed enrichment in immune and inflammatory responses, with a more and higher upregulation of DEGs enriched in the P100-infected group. Notably, the DEGs were concentrated in the MAPK pathway within the P100-infected group, with significant upregulation in EphA2 and c-Fos. Knockdown of EphA2 and c-Fos reduced PDCoV infection and significantly impaired P100 replication compared to P1, suggesting a novel mechanism in which EphA2 and c-Fos are highly involved in passaged virus replication. Our findings illuminate the resemblances and distinctions in the gene expression patterns of host cells infected with P1 and P100, confirming that EphA2 and c-Fos play key roles in high-passage PDCoV replication. These results enhance our understanding of the changes in virulence and replication capacity during the process of passaging.
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RATIONALE: Recurrent laryngeal papillomatosis (RLP) is a common benign tumor in the larynx of children, which is characterized by high recurrence rate and rapid growth, leading to clinical symptoms such as hoarseness and difficulty breathing. Low-temperature plasma radiofrequency ablation (RFA) is the main treatment, but ventilation problems are often encountered during surgery. PATIENT CONCERNS: We report a case of a 2-year-old child with RLP who underwent low-temperature plasma RFA with the assistance of a laryngoscope. However, the surgery had to be temporarily stopped due to ventilation difficulties and difficulty in maintaining blood oxygen saturation during the procedure. DIAGNOSIS: The child was diagnosed with RLP. INTERVENTIONS: The child underwent low-temperature plasma RFA supported by laryngoscopy assisted by ECMO. OUTCOMES: Despite ventilation problems during surgery, the use of ECMO support helped maintain good oxygen saturation in the child and provided a clear surgical field, enabling the tumor to be quickly and cleanly removed. Therefore, the use of ECMO provided critical support during the surgery. LESSONS: This case highlights the importance of airway management during laryngeal papillomatosis surgery. A thorough airway assessment should be performed before anesthesia, and early use of ECMO can reduce harm to the child and ensure the child's safety.