Transport of fluid through a pipe is essential for the operation of macroscale machines and microfluidic devices. Conventional fluids only flow in response to external pressure. We demonstrate that ...an active isotropic fluid, composed of microtubules and molecular motors, autonomously flows through meter-long three-dimensional channels. We establish control over the magnitude, velocity profile, and direction of the self-organized flows and correlate these to the structure of the extensile microtubule bundles. The inherently three-dimensional transition from bulk-turbulent to confined-coherent flows occurs concomitantly with a transition in the bundle orientational order near the surface and is controlled by a scale-invariant criterion related to the channel profile. The nonequilibrium transition of confined isotropic active fluids can be used to engineer self-organized soft machines.
Tumor progression with chemoresistance and local recurrence is commonly happened during treatment of esophageal squamous cell carcinoma (ESCC). Cancer stem cells (CSC) may respond for tumor ...progression. However, there are few reports regarding metabolism of esophageal CSCs with clinical correlation. In this work, we demonstrated that ESCC cell lines in spheroid culture display CSC phenotypes, including increased ALDH activity, chemoresistance and tumor initiation, which are dependent on Hsp27 activation. Esophageal CSCs also exhibit reprogrammed metabolic features particularly higher glycolysis and oxidative phosphorylation, which are regulated via the Hsp27–AKT–HK2 pathway. Moreover, HK2 is required for maintenance of CSC phenotypes. Inhibition of CSC metabolism reduces cell growth and tumor formation. Clinically, patients who underwent surgical resection for esophageal cancer, and displayed overexpression of both Hsp27 and HK2, had the worst prognosis of all expression types. In conclusion, stem cells features and aberrant metabolic reprogramming of esophageal CSCs depend on the Hsp27–AKT–HK2 pathway. Targeting Hsp27 and HK2 could be novel therapeutic strategy for treating esophageal cancer and warrants further investigation.
What's new?
Cancer stem cells (CSC) are suspected of contributing to chemoresistance in esophageal cancer, a role likely made possible by CSC metabolic plasticity and rapid adaptation to changes in tumor microenvironment. Here, human esophageal squamous cancer cells in spheroid culture were found to exhibit key CSC features, including elevated ALDH activity, glycolysis, and oxidative phosphorylation. Hsp27‐AKT‐HK2 pathway upregulation was required for CSC phenotype maintenance. In vivo, inhibition of CSC metabolism successfully blocked tumor growth. While Hsp27 and HK2 upregulation correlates with poor prognosis in patients, the data suggest that Hsp27‐AKT‐HK2 targeting and metabolic inhibition can potentially be used against esophageal cancer.
Active fluid droplets surrounded by oil can spontaneously develop circulatory flows. However, the dynamics of the surrounding oil and their influence on the active fluid remain poorly understood. To ...investigate interactions between the active fluid and the passive oil across their interface, kinesin-driven microtubule-based active fluid droplets were immersed in oil and compressed into a cylinder-like shape. The droplet geometry supported intradroplet circulatory flows, but the circulation was suppressed when the thickness of the oil layer surrounding the droplet decreased. Experiments with tracers and network structure analyses and continuum models based on the dynamics of self-elongating rods demonstrated that the flow transition resulted from flow coupling across the interface between active fluid and oil, with a millimeter-scale coupling length. In addition, two novel millifluidic devices were developed that could trigger and suppress intradroplet circulatory flows in real time: one by changing the thickness of the surrounding oil layer and the other by locally deforming the droplet. This work highlights the role of interfacial dynamics in the active fluid droplet system and shows that circulatory flows within droplets can be affected by millimeter-scale flow coupling across the interface between the active fluid and the oil.
Superconductivity in the PbO-type structure α-FeSe Hsu, Fong-Chi; Luo, Jiu-Yong; Yeh, Kuo-Wei ...
Proceedings of the National Academy of Sciences - PNAS,
09/2008, Letnik:
105, Številka:
38
Journal Article
Recenzirano
Odprti dostop
The recent discovery of superconductivity with relatively high transition temperature (Tc) in the layered iron-based quaternary oxypnictides LaO₁₋xFx FeAs by Kamihara et al. Kamihara Y, Watanabe T, ...Hirano M, Hosono H (2008) Iron-based layered superconductor LaO1-xFx FeAs (x = 0.05-0.12) with Tc = 26 K. J Am Chem Soc 130:3296-3297. was a real surprise and has generated tremendous interest. Although superconductivity exists in alloy that contains the element Fe, LaOMPn (with M = Fe, Ni; and Pn = P and As) is the first system where Fe plays the key role to the occurrence of superconductivity. LaOMPn has a layered crystal structure with an Fe-based plane. It is quite natural to search whether there exists other Fe based planar compounds that exhibit superconductivity. Here, we report the observation of superconductivity with zero-resistance transition temperature at 8 K in the PbO-type α-FeSe compound. A key observation is that the clean superconducting phase exists only in those samples prepared with intentional Se deficiency. FeSe, compared with LaOFeAs, is less toxic and much easier to handle. What is truly striking is that this compound has the same, perhaps simpler, planar crystal sublattice as the layered oxypnictides. Therefore, this result provides an opportunity to better understand the underlying mechanism of superconductivity in this class of unconventional superconductors.
To explore the association between the non-apnea sleep disorder (NSD) and autoimmune diseases.
Cohort study.
Nationwide database research.
84,996 adult patients with NSD diagnoses recorded in the ...Taiwan National Health Insurance Research Database between 2000 and 2003, after excluding those with antecedent autoimmune diseases. A comparison cohort of 84,996 participants was formed by age-, gender-, income-, and urbanization-matched controls.
None.
The two cohorts were followed up for occurrence of autoimmune diseases, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and systemic sclerosis (SSc). A Cox proportional hazards regression model was used for muti-variate adjustment. In patients with NSD, the overall risk for incident autoimmune diseases was significantly higher than in controls (adjusted hazard ratio HR = 1.47, 95% confidence interval CI = 1.41-1.53). With regard to individual diseases, the risks for SLE, RA, AS and SS among NSD patients were also significantly higher than in controls (HR 95% CI for SLE, RA, AS, and SS were 1.81 1.50-2.18, 1.45 1.36-1.54, 1.53 1.38-1.70, and 1.51 1.43-1.60, respectively), whereas the increased risk for SSc did not reach statistical significance (HR: 1.36 0.82-2.26).
Patients with non-apnea sleep disorder were associated with a higher risk for developing autoimmune diseases.
Intermittent hypoxia (IH), characterized as cyclic episodes of short-period hypoxia followed by normoxia, occurs in many physiological and pathophysiological conditions such as pregnancy, athlete, ...obstructive sleep apnea, and asthma. Hypoxia can induce autophagy, which is activated in response to protein aggregates, in the proteotoxic forms of cardiac diseases. Previous studies suggested that autophagy can protect cells by avoiding accumulation of misfolded proteins, which can be generated in response to ischemia/reperfusion (I/R) injury. The objective of the present study was to determine whether IH-induced autophagy can attenuate endoplasmic reticulum (ER) stress and cell death. In this study, H9c2 cell line, rat primary cultured cardiomyocytes, and C57BL/6 male mice underwent IH with an oscillating O
concentration between 4 and 20% every 30 min for 1-4 days in an incubator. The levels of LC3, an autophagy indicator protein and CHOP and GRP78 (ER stress-related proteins) were measured by Western blotting analyses. Our data demonstrated that the autophagy-related proteins were upregulated in days 1-3, while the ER stress-related proteins were downregulated on the second day after IH. Treatment with H
O
(100 μM) for 24 h caused ER stress and increased the level of ER stress-related proteins, and these effects were abolished by pre-treatment with IH condition. In response to the autophagy inhibitor, the level of ER stress-related proteins was upregulated again. Taken together, our data suggested that IH could increase myocardial autophagy as an adaptive response to prevent the ER stress and apoptosis.
Background
Human cytomegalovirus (CMV) is associated with aspergillosis, but the simultaneous presence of CMV viral interleukin‐10 (cmvIL‐10) and aspergillosis has never been investigated. CmvIL‐10 ...is produced by CMV‐infected cells and acts as an immune modulator during CMV infection. The aim of this study was to evaluate cmvIL‐10 levels in peripheral blood and its influence on the clinical outcomes of Aspergillus infection.
Methods
Patients who visited or were admitted to the hospital with suspected Aspergillus infection, including invasive aspergillosis (IA) and chronic pulmonary aspergillosis (CPA), were prospectively enrolled. The cmvIL‐10, human IL‐10 (hIL‐10), IL‐1B, IL‐6, IL‐8, IFN‐γ, and TNF‐α levels in peripheral blood were measured.
Results
Patients with Aspergillus infection had a higher level of cmvIL‐10 than the control group (158 ± 305 vs 27.9 ± 30.4 pg/ml, p < .05). The level of cmvIL‐10 was not correlated with CMV viremia or end‐organ disease. The cmvIL‐10 but not hIL‐10 level was positively correlated with the IFN‐γ level (p < .05) and marginally negatively correlated with IL‐1B and IL‐8 levels (p < .1). In patients with CPA, a high level of cmvIL‐10 (≥100 pg/ml) was a poor prognostic factor for long‐term survival (p < .05). In contrast, CMV viremia or end‐organ disease was associated with poor survival in patients with IA (p = .05).
Conclusions
Aspergillus infection was associated with CMV coinfection with cmvIL‐10 in blood. A cmvIL‐10 concentration ≥100 pg/ml was a predictor for unfavourable outcome in CPA patients.
This study aimed to investigate the proportion of young OSA adults with sleep-related complaints in a sleep center, affiliated with a tertiary medical center for over a decade. This study presents a ...chronicle change in the numbers of young adults receiving polysomnography (PSG) and young patients with OSA from 2000 to 2017. We further analyzed 371 young patients with OSA among 2378 patients receiving PSG in our sleep center from 2016 to 2017 to capture their characteristics. Young adults constituted a substantial and relatively steady portion of examinees of PSG (25.1% ± 2.8%) and confirmed OSA cases (19.8 ± 2.4%) even though the total numbers increased with the years. Young adults with OSA tend to be sleepier, have a greater body mass index, and have a higher percentage of cigarette smoking and alcohol consumption. They also complained more about snoring and daytime sleepiness. They had a higher apnea-hypopnea index on average and experienced more hypoxemia during their sleep, both in terms of duration and the extent of desaturation. Even though the prevalence of comorbidities increased with age, hypertension in young male adults carried higher risks for OSA. Young adults with OSA have constituted a relatively constant portion of all confirmed OSA cases across time. The young adults with OSA were heavier, more symptomatic, and with more severe severity.Clinical trial: The Institutional Review Board of Taipei Veterans General Hospital approved the study (VGHIRB No. 2018-10-002CC). The study is registered with ClinicalTrials.gov, number NCT03885440.
Summary
Sleep disorders are common non‐motor symptoms in patients with Parkinson's disease. Our study aims to explore the relationship between non‐apnea sleep disorders and future Parkinson's ...disease. This is a cohort study using a nationwide database. The participants were recruited from the Taiwan National Health Insurance Research Database between 2000 and 2003. A total of 91 273 adult patients who had non‐apnea sleep disorders without pre‐existing Parkinson's disease were enrolled. An age‐, gender‐, income‐, urbanization‐ and Charlson comorbidity index score‐matched control cohort consisting of 91 273 participants was selected for comparison. The two cohorts were followed for the occurrence of Parkinson's disease, death or until the end of 2010, whichever came first. The Kaplan–Meier analyses revealed patients with non‐apnea sleep disorders tended to develop Parkinson's disease (log‐rank test, P < 0.001). After a multivariate adjustment in a Cox regression model, non‐apnea sleep disorders was an independent risk factor for the development of Parkinson's disease crude hazard ratio: 1.63, 95% confidence interval (CI): 1.54–1.73, P < 0.001; adjusted hazard ratio: 1.18, 95% CI: 1.11–1.26, P < 0.001. In the subgroup analysis, patients with chronic insomnia (lasting more than 3 months) had the greatest risk (crude hazard ratio: 2.91, 95% CI: 2.59–3.26, P < 0.001; adjusted hazard ratio: 1.37, 95% CI: 1.21–1.55, P < 0.001). In conclusion, this study revealed that non‐apnea sleep disorders, especially chronic insomnia, are associated with a higher risk for future Parkinson's disease.
Limited research has investigated the relationship between small airway dysfunction (SAD) and static lung hyperinflation (SLH) in patients with post-acute sequelae of COVID-19 (PASC) especially ...dyspnea and fatigue.
64 patients with PASC were enrolled between July 2020 and December 2022 in a prospective observational cohort. Pulmonary function tests, impulse oscillometry (IOS), and symptom questionnaires were performed two, five and eight months after acute infection. Multivariable logistic regression models were used to test the association between SLH and patient-reported outcomes.
SLH prevalence was 53.1% (34/64), irrespective of COVID-19 severity. IOS parameters and circulating CD4/CD8 T-cell ratio were significantly correlated with residual volume to total lung capacity ratio (RV/TLC). Serum CD8 + T cell count was negatively correlated with forced expiratory volume in the first second (FEV
) and forced vital capacity (FVC) with statistical significance. Of the patients who had SLH at baseline, 57% continued to have persistent SLH after eight months of recovery, with these patients tending to be older and having dyspnea and fatigue. Post-COVID dyspnea was significantly associated with SLH and IOS parameters R5-R20, and AX with adjusted odds ratios 12.4, 12.8 and 7.6 respectively. SLH was also significantly associated with fatigue.
SAD and a decreased serum CD4/CD8 ratio were associated with SLH in patients with PASC. SLH may persist after recovery from infection in a substantial proportion of patients. SAD and dysregulated T-cell immune response correlated with SLH may contribute to the development of dyspnea and fatigue in patients with PASC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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