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Objective: Ongoing symptoms which originated from coronavirus disease 2019 (COVID-19) infections threaten the health of a broad population of patients. With recent changes in COVID-19 control measures in China, medical staff members are currently experiencing a high level of stress. This study aimed to investigate the prevalence of ongoing symptomatic COVID-19 and explore the potential association between stress and ongoing COVID symptoms. Methods: From January 17th to February 2, 2023, primary medical staff members in Jiangsu Province were surveyed using a self-designed questionnaire. Univariate multinomial logistic analysis was used to illustrate the relationship between stress and ongoing symptoms after matching the low- and high-stress groups in a 1:1 ratio based on propensity scores. Results: Analysis revealed that 14.83 % (3785/25,516) of primary medical staff members infected with COVID-19 experienced ongoing symptoms, the most common of which included cough (9.51 %), dyspnea (9.51 %), sleep problems (4.40 %), anxiety (2.29 %), and reproductive system symptoms (1.89 %). In matched patients, higher stress levels were associated with a greater risk of ongoing symptoms than in patients without ongoing symptoms for 14 of the 15 reported symptoms in this study (odds ratios [ORs] > 1 and P < 0.05). Moreover, higher levels of stress were associated with a greater risk of more ongoing symptoms, and the overall ORs increased with the number of symptoms (ORs >1 and P < 0.05). Conclusion: To mitigate the possibility of experiencing ongoing symptoms, healthcare organizations and local authority agencies should institute helpful measures to decrease stress levels such as medical staff augmentation and enabling all staff to have a reasonable work-life balance.
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AIMS: This study aims to investigate the epidemiological characteristics of COVID-19 infection among healthcare workers, including the severity, duration of infection, post-infection symptoms and related influencing factors. METHODS: A self-administered questionnaire was utilized to assess the post-infection status of primary healthcare workers in Jiangsu Province. The questionnaire collected information on demographic characteristics, lifestyle habits, post-infection clinical manifestations, work environment and recovery time of the respondents. Customized outcome events were selected as dependent variables and logistic regression models were employed to analyse the risk factors. Phi-coefficient was used to describe the relationship between post-infection symptoms. RESULTS: The analysis revealed that several factors, such as female, older age, obesity, previous medical history, exposure to high-risk environments and stress, were associated with a higher likelihood of experiencing more severe outcomes. On the other hand, vaccination and regular exercise were found to contribute to an earlier resolution of the infection. Among the post-infection symptoms, cough, malaise and muscle aches were the most frequently reported. Overall, there was a weak association among symptoms persisting beyond 14 days, with only cough and malaise, malaise and dizziness and headache showing a stronger correlation. CONCLUSION: The study findings indicate that the overall severity of the first wave of infection, following the complete lifting of restrictions in China, was low. The impact on primary healthcare workers was limited, and the post-infection symptoms exhibited similarity to those observed in other countries. It is important to highlight that these conclusions are specifically relevant to the population infected with the Omicron variant. IMPACTS: This study helps to grasp the impacts of the first wave of COVID-19 infections on healthcare workers in China after the national lockdown was lifted. PATIENTS: Primary healthcare workers in Jiangsu Province, including doctors, nurses, pharmacists and other personnel from primary healthcare units such as community health service centres and health centres.
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Plasticized polyvinyl chloride (PVC) gel is a new soft and smart material, whose potential in electroactive variable stiffness can be used for vibration control in soft robotic systems. In this paper, a new semi-active vibration absorber is developed by stacking PVC gel actuator units. The absorption bandwidth of a single PVC gel absorber covers the range of three natural frequencies (76.5 Hz, 95 Hz, 124 Hz) of a rectangular steel plate in vibration attenuation. The maximum reduction percentage in acceleration amplitude is 63%. With stacked PVC gel actuator units, the absorption bandwidth can be shifted and obviously broadened.
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BACKGROUND: DEHP, a common plasticizer known for its hormone-disrupting properties, has been associated with asthma. However, a significant proportion of adult asthma cases are "non-atopic", lacking a clear etiology. METHODS: In a case-control study conducted between 2011 and 2015, 365 individuals with current asthma and 235 healthy controls from Kaohsiung City were enrolled. The control group comprised individuals without asthma, Type 2 Diabetes Mellitus (T2DM), hypertension, or other respiratory/allergic conditions. The study leveraged asthma clusters (Clusters A to F) established in a prior investigation. Analysis involved the examination of urinary DEHP metabolites (MEHP and MEHHP), along with the assessment of oxidative stress, sphingolipid metabolites, and inflammatory biomarkers. Statistical analyses encompassed Spearman's rank correlation coefficients, multiple logistic regression, and multinomial logistic regression. RESULTS: Asthma clusters (E, D, C, F, A) exhibited significantly higher ORs of MEHHP exposures compared to the control group. When considering asthma-related comorbidities (T2DM, hypertension, or both), patients without comorbidities demonstrated significantly higher ORs of the sum of primary and secondary metabolites (MEHP + MEHHP) and MEHHP compared to those with asthma comorbidities. A consistent positive correlation between urinary HEL and DEHP metabolites was observed, but a consistent negative correlation between DEHP metabolites and selected cytokines was identified. CONCLUSION: The current study reveals a heightened risk of MEHHP and MEHP + MEHHP exposure in specific asthma subgroups, emphasizing its complex relationship with asthma. The observed negative correlation with cytokines suggests a new avenue for research, warranting robust evidence from epidemiological and animal studies.
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Asma , Diabetes Mellitus Tipo 2 , Dietilexilftalato , Dietilexilftalato/análogos & derivados , Hipertensão , Ácidos Ftálicos , Adulto , Animais , Humanos , Dietilexilftalato/toxicidade , Dietilexilftalato/urina , Exposição Ambiental , Estudos de Casos e Controles , Asma/induzido quimicamente , Asma/diagnóstico , Asma/epidemiologia , CitocinasRESUMO
Despite the development of HER2-targeted drugs, achieving favorable outcomes for patients with HR+/HER2+MBC remains challenging. This study utilized Bayesian Network Meta-analysis to compare the efficacy and safety of anti-HER2 combination regimens. The primary analysis focused on progression-free survival (PFS), while secondary analyses included objective response rate, overall survival (OS) and the incidence rate of grade 3/4 adverse events (AEs). A comprehensive search across seven databases identified 25 randomized controlled trials for inclusion in this meta-analysis. For patients eligible for endocrinotherapy, our findings revealed that dual-target combined endocrine therapy, such as Her2-mAb+Her2-mAb+Endo (HR = 0.38; 95%CrI: 0.16-0.88) and Her2-mAb+Her2-tki+Endo (HR = 0.45; 95%CrI: 0.23-0.89), significantly improved PFS compared to endocrine therapy alone. According to the surface under the cumulative ranking curves (SUCRAs), Her2-mAb+Her2-mAb+Endo and Her2-mAb+Her2-tki+Endo ranked highest in terms of PFS and OS, respectively. For patients unsuitable for endocrine therapy, anti-HER2 dual-target combined chemotherapy, such as Her2-mAb+Her2-mAb+Chem (HR = 0.76; 95%CrI: 0.6-0.96) and Her2-mAb+Her2-tki+Chem (HR = 0.48; 95%CrI: 0.29-0.81), demonstrated significant improvements in PFS compared to Her2-mAb+Chem. The results were the same when compared with Her2-tki+Chem. According to the SUCRAs, Her2-mAb+Her2-tki+Chem and Her2-mAb+Her2-mAb+Chem ranked highest for PFS and OS, respectively. Subgroup analyses consistently supported these overall findings, indicating that dual-target therapy was the optimal approach irrespective of treatment line.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Teorema de Bayes , Metanálise em Rede , Bases de Dados Factuais , Intervalo Livre de ProgressãoRESUMO
BACKGROUND: Timely medical intervention in severe cases of coronavirus disease 2019 (COVID-19) and better understanding of the disease's pathogenesis are essential for reducing mortality, but early classification of severe cases and its progression is challenging. OBJECTIVE: We investigated the levels of circulating phospholipid metabolites and their relationship with COVID-19 severity, as well as the potential role of phospholipids in disease progression. METHODS: We performed nontargeted lipidomic analysis of plasma samples (n = 150) collected from COVID-19 patients (n = 46) with 3 levels of disease severity, healthy individuals, and subjects with metabolic disease. RESULTS: Phospholipid metabolism was significantly altered in COVID-19 patients. Results of a panel of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) and of phosphatidylethanolamine and lysophosphatidylethanolamine (LPE) ratios were significantly correlated with COVID-19 severity, in which 16 phospholipid ratios were shown to distinguish between patients with severe disease, mild disease, and healthy controls, 9 of which were at variance with those in subjects with metabolic disease. In particular, relatively lower ratios of circulating (PC16:1/22:6)/LPC 16:1 and (PE18:1/22:6)/LPE 18:1 were the most indicative of severe COVID-19. The elevation of levels of LPC 16:1 and LPE 18:1 contributed to the changes of related lipid ratios. An exploratory functional study of LPC 16:1 and LPE 18:1 demonstrated their ability in causing membrane perturbation, increased intracellular calcium, cytokines, and apoptosis in cellular models. CONCLUSION: Significant Lands cycle remodeling is present in patients with severe COVID-19, suggesting a potential utility of selective phospholipids with functional consequences in evaluating COVID-19's severity and pathogenesis.
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COVID-19 , Fosfolipídeos , Humanos , Fosfolipídeos/metabolismo , Lisofosfatidilcolinas/metabolismoRESUMO
BACKGROUND: Adult asthma is phenotypically heterogeneous with unclear aetiology. We aimed to evaluate the potential contribution of environmental exposure and its ensuing response to asthma and its heterogeneity. METHODS: Environmental risk was evaluated by assessing the records of National Health Insurance Research Database (NHIRD) and residence-based air pollution (particulate matter with diameter less than 2.5 micrometers (PM2.5) and PM2.5-bound polycyclic aromatic hydrocarbons (PAHs)), integrating biomonitoring analysis of environmental pollutants, inflammatory markers and sphingolipid metabolites in case-control populations with mass spectrometry and ELISA. Phenotypic clustering was evaluated by t-distributed stochastic neighbor embedding (t-SNE) integrating 18 clinical and demographic variables. FINDINGS: In the NHIRD dataset, modest increase in the relative risk with time-lag effect for emergency (N=209 837) and outpatient visits (N=638 538) was observed with increasing levels of PM2.5 and PAHs. Biomonitoring analysis revealed a panel of metals and organic pollutants, particularly metal Ni and PAH, posing a significant risk for current asthma (ORs=1.28-3.48) and its severity, correlating with the level of oxidative stress markers, notably Nε-(hexanoyl)-lysine (r=0.108-0.311, p<0.05), but not with the accumulated levels of PM2.5 exposure. Further, levels of circulating sphingosine-1-phosphate and ceramide-1-phosphate were found to discriminate asthma (p<0.001 and p<0.05, respectively), correlating with the levels of PAH (r=0.196, p<0.01) and metal exposure (r=0.202-0.323, p<0.05), respectively, and both correlating with circulating inflammatory markers (r=0.186-0.427, p<0.01). Analysis of six phenotypic clusters and those cases with comorbid type 2 diabetes mellitus (T2DM) revealed cluster-selective environmental risks and biosignatures. INTERPRETATION: These results suggest the potential contribution of environmental factors from multiple sources, their ensuing oxidative stress and sphingolipid remodeling to adult asthma and its phenotypic heterogeneity.
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Poluentes Atmosféricos , Poluição do Ar , Asma , Diabetes Mellitus Tipo 2 , Hidrocarbonetos Policíclicos Aromáticos , Adulto , Humanos , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Esfingolipídeos , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Material Particulado/toxicidade , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Monitoramento Ambiental/métodosRESUMO
Introduction: In times of epidemic outbreaks, healthcare workers (HCWs) emerge as a particularly vulnerable group. This cross-sectional study endeavors to assess the COVID-19 infection rate among the primary HCWs in Jiangsu Province subsequent to the implementation of adjusted epidemic prevention and control strategies. Methods: From January 17 to February 2, 2023, an extensive survey was conducted among primary HCWs in Jiangsu Province, employing a self-designed questionnaire. Logistic regression analysis was utilized to identify the factors associated with COVID-19 infection. Results: The overall infection rate among primary HCWs stood at 81.05%, with a 95% confidence interval (CI) of 80.61-81.48%. Among those afflicted, cough, fatigue, and fever emerged as the three most prevalent symptoms, each with an incidence rate exceeding 80%. In the context of multivariate logistic regression, an elevated risk of COVID-19 infection was observed in correlation with female gender (adjusted odds ratio [aOR] = 1.12, 95% CI: 1.04-1.21), possessing a bachelor's degree or higher (aOR = 1.32, 95% CI: 1.23-1.41), accumulating over 10 years of work experience (aOR = 1.28, 95% CI: 1.11-1.47), holding a middle-level cadre position (aOR = 1.22, 95% CI: 1.11-1.35), assuming the role of a unit leader (aOR = 1.30, 95% CI: 1.11-1.54), and working in a fever clinic for 1 to 10 days per month (aOR = 1.42, 95% CI: 1.29-1.57). Conversely, advanced age (aOR = 0.76, 95% CI: 0.70-0.82), being underweight (aOR = 0.78, 95% CI: 0.69-0.90), current smoking (aOR = 0.64, 95% CI: 0.57-0.71), receiving 4 doses of COVID-19 vaccine (aOR = 0.49, 95% CI: 0.37-0.66), and pregnancy or perinatal status (aOR = 0.85, 95% CI: 0.72-0.99) were associated with a diminished risk of infection. Conclusion: Following the implementation of adjusted policies, a substantial proportion of primary HCWs in Jiangsu province contracted COVID-19. Female gender and younger age emerged as risk factors for COVID-19 infection, while no discernible link was established between professions and COVID-19 susceptibility. The receipt of COVID-19 vaccines demonstrated efficacy in curtailing the infection rate, underscoring the significance of bolstering prevention knowledge and heightening self-protective awareness among primary HCWs.
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COVID-19 , Gravidez , Humanos , Feminino , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos Transversais , China/epidemiologia , Febre , Pessoal de SaúdeRESUMO
AIMS: Peripherally inserted central catheters (PICCs) are becoming common and effective in acute and critical care settings recently. Burn patients need special considerations because of restricted insertion sites, burn wounds, hyper coagulation, high infection rates and others. However, the safety of PICCs in burn patients are not well elucidated and no related protocol has been formed. This study aims to investigate the thrombosis and infections of PICCs in burn patients. METHODS: This was a single center retrospective study and a systematic review. All the burn patients with PICCs between January 1, 2018 and December 31, 2020 were included. A systematic search of Medline, PubMed, EMBASE and Web of Science was performed from inception to 4 June 2021 following PRISMA guidelines. Upper extremity vein thrombosis (UEVT) and central line-associated bloodstream infection (CLABSI) were the main outcome. RESULTS: A total of 85 successful PICCs in 78 patients were included. Most patients were male (79.5%), adults(80.8%) and injured by flame(74.4%). The mean TBSA was 50.3% and 76.9% of patients had TBSA more than 30%. Most PICCs were punctured once (60.0%) and inserted less than 30 days after injury (80.0%) through basilar vein (70.6%). The overall line days were 2195 days and the mean line days was 25.8 ± 18.3 days. Six PICCs were complicated by UEVT (7.1%) in 21.2 ± 17.3 days after insertion. Patients with UEVT had significantly higher rate of bacteremia and later insertions than those without UEVT. One patient developed CLABSI and the CLABSI rate was 1.2% and 0.5 per 1000 line days. Six PICCs had catheter colonization. No significant risk factors were identified. Five articles involving 293 patients and 319 PICCs were ultimately evaluated in systematic review. The overall incidence of UEVT was 3.2% and CLABSI was 6.9% in burn populations. CONCLUSION: PICCs in burn patients had acceptable incidence of UEVT and CLABSI with relative long line durations. A standardized PICC guideline for burn patients is required to further improve the feasibility and safety of PICCs.
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Queimaduras , Cateterismo Venoso Central , Trombose , Adulto , Humanos , Masculino , Feminino , Cateterismo Venoso Central/efeitos adversos , Estudos Retrospectivos , Queimaduras/epidemiologia , Queimaduras/terapia , Queimaduras/etiologia , Trombose/epidemiologia , Trombose/etiologia , CatéteresRESUMO
Introduction: Green sea turtles are endangered marine reptiles. Carapacial ulcers will develop on juvenile green sea turtles during artificial rescue, seriously affecting their health and potentially leading to death. Methods: To determine the pathogens causing ulcerative carapacial disease, we performed 16S and ITS high-throughput sequencing, and microbial diversity analysis on samples from carapacial ulcers, healthy carapaces, feces, and seawater of juvenile green sea turtles. Results: Our analysis showed that changes in microbial diversity of green sea turtle feces and seawater were not significantly associated with ulcerative carapacial disease. Discussion: Psychrobacter sp. is the dominant species in the carapacial ulcers of green sea turtles. The bacterium is present in both healthy turtles and seawater where carapacial ulcers did not occur and decreasing seawater temperatures are likely responsible for the infection of juvenile green turtles with Psychrobacter sp. This is the first study on carapacial ulcers in captive juvenile green sea turtles. Our research provides theoretical guidance for the prevention and control of carapacial ulcers in captive juvenile green sea turtles.
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The aryl hydrocarbon receptor (AhR) is a ligand-binding protein that responds to environmental aromatic hydrocarbons and stimulates the transcription of downstream phase I enzyme-related genes by binding the cis element of dioxin-responsive elements (DREs)/xenobiotic-responsive elements. Dimethyl sulfoxide (DMSO) is a well-known organic solvent that is often used to dissolve phase I reagents in toxicology and oxidative stress research experiments. In the current study, we discovered that 0.1% DMSO significantly induced the activation of the AhR promoter via DREs and produced reactive oxygen species, which induced apoptosis in mouse embryonic fibroblasts (MEFs). Moreover, Jun dimerization protein 2 (Jdp2) was found to be required for activation of the AhR promoter in response to DMSO. Coimmunoprecipitation and chromatin immunoprecipitation studies demonstrated that the phase I-dependent transcription factors, AhR and the AhR nuclear translocator, and phase II-dependent transcription factors such as nuclear factor (erythroid-derived 2)-like 2 (Nrf2) integrated into DRE sites together with Jdp2 to form an activation complex to increase AhR promoter activity in response to DMSO in MEFs. Our findings provide evidence for the functional role of Jdp2 in controlling the AhR gene via Nrf2 and provide insights into how Jdp2 contributes to the regulation of ROS production and the cell spreading and apoptosis produced by the ligand DMSO in MEFs.
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Dibenzodioxinas Policloradas , Receptores de Hidrocarboneto Arílico , Animais , Dimetil Sulfóxido/farmacologia , Fibroblastos/metabolismo , Ligantes , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Dibenzodioxinas Policloradas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismoRESUMO
Hypervirulent Klebsiella pneumoniae (hvKP) with a high mucus phenotype, can cause liver abscess and extrahepatic invasive infection. The morbidity of hvKP infections has increased recently. Here we describe a case report of septicemia caused by hvKP due to the term septic arthritis of right knee joint in a 29-year-old male. The patient was persistent fever with a peak temperature at 40.6 °C. However, based on the drug sensitivity, the treatment failed frequently. The patient did not improve clinically on susceptible monotherapy antimicrobial. Combination therapy with meropenem and rifampicin (RFP) lead to clinical improvement and discharge.
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Electroactive PVC gel is a new artificial muscle material with good performance that can mimic the movement of biological muscle in an electric field. However, traditional manufacturing methods, such as casting, prevent the broad application of this promising material because they cannot achieve the integration of the PVC gel electrode and core layer, and at the same time, it is difficult to create complex and diverse structures. In this study, a multi-material, integrated direct writing method is proposed to fabricate corrugated PVC gel artificial muscle. Inks with suitable rheological properties were developed for printing four functional layers, including core layers, electrode layers, sacrificial layers, and insulating layers, with different characteristics. The curing conditions of the printed CNT/SMP inks under different applied conditions were also discussed. The structural parameters were optimized to improve the actuating performance of the PVC gel artificial muscle. The corrugated PVC gel with a span of 1.6 mm had the best actuating performance. Finally, we printed three layers of corrugated PVC gel artificial muscle with good actuating performance. The proposed method can help to solve the inherent shortcomings of traditional manufacturing methods of PVC gel actuators. The printed structures have potential applications in many fields, such as soft robotics and flexible electronic devices.
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Soft robots are able to generate large and compliant deformation in an unconstructed environment, but their operation capability is limited by low stiffness. Thus, developing the function of variable stiffness while preserving its compliance is a challenging issue. This study proposes a new variable stiffness artificial muscle, as a complementary component for soft robots, using the principle of fringe electric field adhesion. Taking inspiration from the mechanism of multi-layer structures in biological muscles, the artificial muscle is composed of patterned conductive layers and interlayers and is 3D printable by direct ink writing (DIW). To further demonstrate the application, a vibration absorber by stacking this artificial muscle is proposed, whose natural frequency is tunable by the varying stiffness. The advantages of the fringe electric field-enabled variable stiffness (FEVS) artificial muscles include lightweight and irrelevance of the stiffness to the thickness of the interlayer, which can be beneficial to soft robots to achieve variable stiffness and semi-active vibration attenuation without extra weighting load.
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Robótica , Vibração , Eletricidade , MúsculosRESUMO
COVID-19 pandemic is sweeping the globe. Any outpatient or new inpatient especial in burn department during the pandemic should be as a potential infectious source of COVID-19. It is very important to manage the patients and wards carefully and correctly to prevent epidemic of the virus in burn centers. This paper provides some strategies regarding management of burn ward during the epidemic of COVID-19 or other respiratory infectious diseases.
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Queimaduras/terapia , Infecções por Coronavirus , Atenção à Saúde/organização & administração , Controle de Infecções/métodos , Pandemias , Pneumonia Viral , COVID-19 , HumanosRESUMO
Twisted and coiled polymer actuators (TCAs) are a kind of efficient artificial muscles, which have good prospects for application in soft robots, bionic devices, and biological, medical, and other high-tech fields. However, the inability to dynamically sense and adjust the strain of the actuator will lead to uncertainty in the accuracy of deformation and strain, resulting in imprecise target action. Herein, TCAs with strain self-sensing ability (TCASA) are prepared by integrating the stretchable optomechanical film (SOMF) sensors into TCAs, which provides a simple strategy for dynamical strain sensing. These SOMFs have a wide range of color changes during deformation of TCAs, and the strain is perceived by observing the color change according to the corresponding relationship between color change and strain. Furthermore, the proposed TCASA maintain excellent cycling stability of strain self-sensing during cyclic tests (200 cycles) and excellent strain self-sensing performance to perform strain control compared to TCAs without SOMFs. The results indicate that the proposed structure is a promising soft actuator with excellent strain self-sensing ability, which is well suited for soft robots, bionic devices, biological and medical fields, smart wearable technologies, and so forth, especially when controlled, repetitive deformations are required.
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BACKGROUND: Epidemiologic evidence suggests that exposure to particulate matter of 2.5 µm or less in diameter (PM2.5) aggravates asthma. OBJECTIVE: We sought to investigate the underlying mechanisms between PM2.5 exposure and asthma severity. METHODS: The relationship between PM2.5 exposure and asthma severity was investigated in an asthma model with CD4+ T cell-specific aryl hydrocarbon receptor (AhR)-null mice. Effects of PM2.5 and polycyclic aromatic hydrocarbons (PAHs) on differentiation of TH17/regulatory T (Treg) cells were investigated by using flow cytometry and quantitative RT-PCR. Mechanisms were investigated by using mRNA sequencing, chromatin immunoprecipitation, bisulfite sequencing, and glycolysis rates. RESULTS: PM2.5 impaired differentiation of Treg cells, promoted differentiation of TH17 cells, and aggravated asthma in an AhR-dependent manner. PM2.5 and one of its prominent PAHs, indeno[1,2,3-cd]pyrene (IP), promoted differentiation of TH17 cells by upregulating hypoxia-inducible factor 1α expression and enhancing glycolysis through AhRs. Exposure to PM2.5 and IP enhanced glutamate oxaloacetate transaminase 1 (Got1) expression through AhRs and accumulation of 2-hydroxyglutarate, which inhibited ten-eleven translocation methylcytosine dioxygenase 2 activity, resulting in hypermethylation in the forkhead box P3 locus and impaired differentiation of Treg cells. A GOT1 inhibitor, (aminooxy)acetic acid, ameliorated asthma by shifting differentiation of TH17 cells to Treg cells. Similar regulatory effects of exposure to PM2.5 or IP on TH17/Treg cell imbalance were noted in human T cells, and in a case-control design PAH exposure appeared to be a potential risk factor for asthma. CONCLUSIONS: The AhR-hypoxia-inducible factor 1α and AhR-GOT1 molecular pathways mediate pulmonary responses on exposure to PM2.5 through their ability to disturb the balance of TH17/Treg cells.
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Aspartato Aminotransferase Citoplasmática/imunologia , Asma/imunologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/imunologia , Material Particulado/toxicidade , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Animais , Aspartato Aminotransferase Citoplasmática/genética , Asma/induzido quimicamente , Asma/genética , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Modelos Animais de Doenças , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Camundongos , Camundongos Mutantes , Tamanho da Partícula , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/imunologia , Linfócitos T Reguladores/patologia , Células Th17/patologiaRESUMO
Aryl hydrocarbon receptor (AhR), a cellular chemical sensor, controls cellular homeostasis, and sphingosine-1-phosphate (S1P), a bioactive intermediate of sphingolipid metabolism, is believed to have a role in immunity and inflammation, but their potential crosstalk is currently unknown. We aimed to determine whether there is a functional linkage between AhR signaling and sphingolipid metabolism. We showed that AhR ligands, including an environmental polycyclic aromatic hydrocarbon (PAH), induced S1P generation, and inhibited S1P lyase (S1PL) activity in resting cells, antigen/IgE-activated mast cells, and mouse lungs exposed to the AhR ligand alone or in combination with antigen challenge. The reduction of S1PL activity was due to AhR-mediated oxidation of S1PL at residue 317, which was reversible by the addition of an antioxidant or in cells with knockdown of the ORMDL3 gene encoding an ER transmembrane protein, whereas C317A S1PL mutant-transfected cells were resistant to the AhR-mediated effect. Furthermore, analysis of AhR ligand-treated cells showed a time-dependent increase of the ORMDL3-S1PL complex, which was confirmed by FRET analysis. This change increased the S1P levels, which in turn, induced mast cell degranulation via S1PR2 signaling. In addition, elevated levels of plasma S1P were found in children with asthma compared to non-asthmatic subjects. These results suggest a new regulatory pathway whereby the AhR-ligand axis induces ORMDL3-dependent S1P generation by inhibiting S1PL, which may contribute to the expression of allergic diseases.
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Aldeído Liases/metabolismo , Hipersensibilidade/metabolismo , Mastócitos/imunologia , Animais , Células Cultivadas , Humanos , Imunoglobulina E/metabolismo , Lisofosfolipídeos/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais , Esfingosina/análogos & derivados , Esfingosina/metabolismoRESUMO
Direct writing techniques for the printing of colloidal multiwalled carbon nanotubes (CNTs) embedded in polydimethylsiloxane (PDMS) were developed herein to fabricate complex structures including woodpiles, tetragonal scaffolds, and gradient mesh structures. The multiwalled CNTs served as a conductive filler and thickening agent for the printing ink. A suitable rheological behavior was obtained by mixing the CNTs with PDMS dissolved in an isopropyl alcohol solvent. A 7 wt % CNT loading in the PDMS was optimum for printing gap-spanning features at a nozzle moving speed of 20 mm/s. The printed structures, including a woodpile and gradient mesh structure, were capable of detecting changes in external mechanical pressure. Printed CNT/PDMS strips exhibit electrical actuation with good mechanical performance (strain of 8.9%) at a low actuation voltage (60 V). The performance characterization and application display demonstrated the possibility of developing custom complex CNT/PDMS structures for a broad range of applications, including soft robots and flexible electronic devices.
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In this article, published online 23 March 2018, the affiliation 10 of Zhou Y was incorrect. The affiliation should be "Children's Hospital and Institute of Biomedical Sciences, Fudan University. Key Laboratory of Neonatal Disease, Ministry of Health, 201102, Shanghai, China." The authors regret the errors.