Summary Background In 2015, a large outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection occurred following a single patient exposure in an emergency room at the Samsung ...Medical Center, a tertiary-care hospital in Seoul, South Korea. We aimed to investigate the epidemiology of MERS-CoV outbreak in our hospital. Methods We identified all patients and health-care workers who had been in the emergency room with the index case between May 27 and May 29, 2015. Patients were categorised on the basis of their exposure in the emergency room: in the same zone as the index case (group A), in different zones except for overlap at the registration area or the radiology suite (group B), and in different zones (group C). We documented cases of MERS-CoV infection, confirmed by real-time PCR testing of sputum samples. We analysed attack rates, incubation periods of the virus, and risk factors for transmission. Findings 675 patients and 218 health-care workers were identified as contacts. MERS-CoV infection was confirmed in 82 individuals (33 patients, eight health-care workers, and 41 visitors). The attack rate was highest in group A (20% 23/117 vs 5% 3/58 in group B vs 1% 4/500 in group C; p<0·0001), and was 2% (5/218) in health-care workers. After excluding nine cases (because of inability to determine the date of symptom onset in six cases and lack of data from three visitors), the median incubation period was 7 days (range 2–17, IQR 5–10). The median incubation period was significantly shorter in group A than in group C (5 days IQR 4–8 vs 11 days 6–12; p<0·0001). There were no confirmed cases in patients and visitors who visited the emergency room on May 29 and who were exposed only to potentially contaminated environment without direct contact with the index case. The main risk factor for transmission of MERS-CoV was the location of exposure. Interpretation Our results showed increased transmission potential of MERS-CoV from a single patient in an overcrowded emergency room and provide compelling evidence that health-care facilities worldwide need to be prepared for emerging infectious diseases. Funding None.
Previous study identified E2F1 as a key mediator of non-muscle-invasive bladder cancer (NMIBC) progression. The aim of this study was to identify the E2F1-related genes associated with poor prognosis ...and aggressive characteristics of bladder cancer.
Microarray analysis was performed to find E2F1-related genes associated with tumor progression and aggressiveness in the gene expression data from 165 primary patients with bladder cancer. The biologic activity of E2F1-related genes in tumor progression and aggressiveness was confirmed with experimental assays using bladder cancer cells and tumor xenograft assay.
The expression of E2F1 was significantly associated with EZH2 and SUZ12. The overexpression of E2F1, EZH2, and SUZ12 enhanced cancer progression including cell colony formation, migration, and invasiveness. Knockdown of these genes reduced motility, blocked invasion, and decreased tumor size in vivo. E2F1 bound the proximal EZH2 and SUZ12 promoter to activate transcription, suggesting that E2F1 and its downstream effectors, EZH2 and SUZ12, could be important mediators for the cancer progression. In addition, we confirmed an association between these genes and aggressive characteristics. Interestingly, the treatment of anticancer drugs to the cells overexpressing E2F1, EZH2, and SUZ12 induced the expression of CD44, KLF4, OCT4, and ABCG2 known as cancer stem cell (CSC)-related genes.
The link between E2F1, EZH2, and/or SUZ12 revealed that E2f1 directly regulates transcription of the EZH2 and SUZ12 genes. The signature of E2F1-EZH2-SUZ12 shows a predictive value for prognosis in bladder tumors and the E2F1-EZH2-SUZ12-driven transcriptional events may regulate the cancer aggressiveness and chemo-resistance, which may provide opportunity for development of new treatment modalities.
Inorganic‐based micro light‐emitting diodes (µLEDs) have witnessed significant improvements in terms of display and biomedical applications, which can shift the paradigm of future optoelectronic ...systems. In particular, µLED displays are on the verge of becoming the next big interface platform for visual communications, expanding to various internet of things and wearable/bioapplications. Novel µLED concepts need to be upgraded to be able to satisfy their potential optoelectric applications, such as virtual reality, smart watches, and medical sensors for individual computing in this hyperconnected society. Here, representative progresses in the field of flexible µLEDs are reviewed with regard to device structures, massive µLED transfers, methods for performance enhancement, and applications.
Inorganic‐based micro light‐emitting diodes (µLEDs) can shift the paradigm of future optoelectronic systems, expanding to various internet of things and wearable/bioapplications. The comprehensive review described in this paper summarizes the recent progress in the areas of flexible µLEDs with regards to device structures, massive µLED transfers, methods for performance enhancement and applications.
Soot particles emitted from vehicles are one of the major sources of air pollution in urban areas. In this study, five kinds of trees were selected as
Pinus densiflora,
Taxus cuspidata,
Platanus ...occidentalis,
Zelkova serrata, and
Ginkgo biloba, and the removal of submicron (<1 μm) and ultrafine (<0.1 μm) soot particles by tree leaves was quantitatively compared in terms of deposition velocity. Soot particles were produced by a diffusion flame burner using acetylene as the fuel. The sizes of monodisperse soot particles classified with the Differential Mobility Analyzers (DMA) were 30, 55, 90, 150, 250, 400, and 600 nm. A deposition chamber was designed to simulate the omni-directional flow condition around the tree leaves. Deposition velocities onto the needle-leaf trees were higher than those onto the broadleaf trees.
P. densiflora showed the greatest deposition velocity, followed by
T. cuspidata,
Platanus occidentalis,
Zelkova serrata, and
Ginkgo biloba. In addition, from the comparison of deposition velocity between two groups of
Platanus occidentalis leaves, i.e. one group of leaves with front sides only and the other with back sides only, it was supposed in case of the broadleaf trees that the removal of airborne soot particles of submicron and ultrafine sizes could be affected by the surface roughness of tree leaves, i.e. the veins and other structures on the leaves.
► Submicron and ultrafine soot particle removal by tree leaves was investigated. ► Deposition velocity was used for the quantitative comparison of particle removal. ►
Pinus densiflora showed the greatest deposition velocity, followed by. ►
Taxus cuspidata,
Platanus occidentalis,
Zelkova serrata, and
Ginkgo biloba. ► Airborne soot particle removal can be affected by surface roughness of tree leaves.
We investigated the effect of resistance training on irisin expression with improvement in muscle strength and function in aged mice and human. In the mice study, 19months old male C57BL/6 mice were ...randomly assigned into two groups; control group and resistance exercise group. Ladder climbing exercise with tail weight was performed 3days per week for 12weeks. In the human study, participants (aged over 65years) were randomly assigned into exercise group or control group. Elastic band exercise program consisted of 12weeks of 1-h session 2days per week. In the mice study, we found an increase of irisin in serum and soleus muscle as well as improvement in muscle strength (p=0.02) and muscle quality (p=0.03) without body composition change in training animals. In the human study, isokinetic leg strength and grip strength were improved in the exercise group compared to the control group without change of body composition. In addition, the level of circulating irisin level was increased. It had a positive correlation with grip strength (R=0.526, p=0.002) and leg strength (R=0.414, p=0.003) in the exercise group. Thus, resistant training might be an efficient intervention method to increase irisin levels and prevent age-related decline in muscle function.
•We investigated the effect of resistance training on the levels of irisin in old mice and human.•Circulating level of irisin was significantly increased following resistance training in both old mice and human.•Increment of circulating irisin induced by resistance training was highly correlated with improvement of physical function.
The antitumor activity of fucoidan from Fucus vesiculosus was investigated in human colon carcinoma cells. The crude fucoidan, a polysaccharide composed predominantly of sulfated fucose, markedly ...inhibited the growth of HCT-15 cells (human colon carcinoma cells). After HCT-15 cells were treated with fucoidan, several apoptotic events such as DNA fragmentation, chromatin condensation and increase of the population of sub-G1 hypodiploid cells were observed. In the mechanism of fucoidan-induced apoptosis, we examined changes in Bcl-2 and Bax protein expression levels and activation of caspases. Fucoidan decreased Bcl-2 expression, whereas the expression of Bax was increased in a time-dependent manner compared to the control. In addition, the active forms of caspase-9 and caspase-3 were increased, and the cleavage of poly(ADP-ribose) polymerase (PARP), a vital substrate of effector caspase, was observed. Furthermore, the induction of apoptosis was also accompanied by a strong activation of extracellular signal-regulated kinase (ERK) and p38 kinase and an inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt in a time-dependent manner. These findings provide evidence demonstrating that the pro-apoptotic effect of fucoidan is mediated through the activation of ERK, p38 and the blocking of the PI3K/Akt signal pathway in HCT-15 cells. These data support the hypothesis that fucoidan may have potential in colon cancer treatment.
AMP-activated protein kinase (AMPK) is a metabolic sensor that maintains energy homeostasis. AMPK functions as a tumor suppressor in different cancers; however, its role in regulating antitumor ...immunity, particularly the function of regulatory T cells (Tregs), is poorly defined.
AMPKα1
Foxp3
, Foxp3
, Rag1
, and C57BL/6 J mice were used for our research. Flow cytometry and cell sorting, western blotting, immuno-precipitation, immuno-fluorescence, glycolysis assay, and qRT-PCR were used to investigate the role of AMPK in suppressing programmed cell death 1 (PD-1) expression and for mechanistic investigation.
The deletion of the AMPKα1 subunit in Tregs accelerates tumor growth by increasing the expression of PD-1. Metabolically, loss of AMPK in Tregs promotes glycolysis and the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), a key enzyme of the mevalonate pathway. Mechanistically, AMPK activates the p38 mitogen-activated protein kinase (MAPK) that phosphorylates glycogen synthase kinase-3β (GSK-3β), inhibiting the expression of PD-1 in Tregs.
Our study identified an AMPK regulatory mechanism of PD-1 expression via the HMGCR/p38 MAPK/GSK3β signaling pathway. We propose that the AMPK activator can display synergic antitumor effect in murine tumor models, supporting their potential clinical use when combined with anti-PD-1 antibody, anti-CTLA-4 antibody, or a HMGCR inhibitor.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Advent and fast spread of pandemic diseases draw worldwide attention to rapid, prompt, and accurate molecular diagnostics with technical development of ultrafast polymerase chain reaction (PCR). ...Microfluidic on-chip PCR platforms provide highly efficient and small-volume bioassay for point-of-care diagnostic applications. Here we report ultrafast, real-time, and on-chip nanoplasmonic PCR for rapid and quantitative molecular diagnostics at point-of-care level. The plasmofluidic PCR chip comprises glass nanopillar arrays with Au nanoislands and gas-permeable microfluidic channels, which contain reaction microchamber arrays, a precharged vacuum cell, and a vapor barrier. The on-chip configuration allows both spontaneous sample loading and microbubble-free PCR reaction during which the plasmonic nanopillar arrays result in ultrafast photothermal cycling. After rapid sample loading less than 3 min, two-step PCR results for 40 cycles show rapid amplification in 264 s for lambda-DNA, and 306 s for plasmids expressing SARS-CoV-2 envelope protein. In addition, the in situ cyclic real-time quantification of amplicons clearly demonstrates the amplification efficiencies of more than 91%. This PCR platform can provide rapid point-of-care molecular diagnostics in helping slow the fast-spreading pandemic.
Diabetes is a disease condition characterized by a prolonged, high blood glucose level, which may lead to devastating outcomes unless properly managed. Here, we introduce a simple camera-based ...optical monitoring system (OMS) utilizing the nanoparticle embedded contact lens that produces color changes matching the tear glucose level without any complicated electronic components. Additionally, we propose an image processing algorithm that automatically optimizes the measurement accuracy even in the presence of image blurring, possibly caused by breathing, subtle movements, and eye blinking. As a result, using in vivo mouse models and human tear samples we successfully demonstrated robust correlations across the glucose concentrations measured by three different independent techniques, validating the quantitative efficacy of the proposed OMS. For its methodological simplicity and accessibility, our findings strongly support that the innovation offered by the OMS and processing algorithm would greatly facilitate the glucose monitoring procedure and improve the overall welfare of diabetes patients.
•EM absorbing properties of Z-type hexaferrite-epoxy composites have been investigated.•Z-hexaferrite exhibits a strong EM wave absorbing performance with RLmin < −50 dB at around the FMR ...frequency.•The frequency of RL peak changes according to the FMR frequency shift induced by an external H-field.
Sr3Co2Fe24O41 hexaferrite powders were prepared via sol-gel synthesis and calcination. The hexaferrite powders after calcination in the temperature range of 1225–1245 °C had almost a single Z-type phase. The Z-type hexaferrite-epoxy (10 wt%) composite sample exhibits ferromagnetic resonance (FMR) at 2.9 GHz and strong electromagnetic (EM) wave absorbing performance with the lowest reflection loss (RLmin) < −50 dB around the FMR frequency. The FMR frequency gradually shifted to 3.9 and 6.5 GHz when external magnetic fields (H) of 250 and 450 Oe were applied, respectively. It is demonstrated that EM wave absorption in the hexaferrite-epoxy composites arises from ferromagnetic resonances (FMR) in the gigahertz band. The frequency of RLmin changes in accordance with the shift in the FMR frequency induced by an external magnetic field. The Z-type hexaferrite–epoxy composite is a highly promising material for EM wave absorption in the gigahertz band (2–10 GHz).