Resveratrol, a phytochemical found in various plants and Chinese herbs, is associated with multiple tumor-suppressing activities, has been tested in clinical trials. However, the molecular mechanisms ...involved in resveratrol-mediated tumor suppressing activities are not yet completely defined. Here, we showed that treatment with resveratrol inhibited cell mobility through induction of the mesenchymal-epithelial transition (MET) in lung cancer cells. We also found that downregulation of FOXC2 (forkhead box C2) is critical for resveratrol-mediated suppression of tumor metastasis in an in vitro and in vivo models. We also identified a signal cascade, namely, resveratrol-∣miRNA-520h-∣PP2A/C-∣Akt → NF-κB → FOXC2, in which resveratrol inhibited the expression of FOXC2 through regulation of miRNA-520h-mediated signal cascade. This study identified a new miRNA-520h-related signal cascade involved in resveratrol-mediated tumor suppression activity and provide the clinical significances of miR-520h, PP2A/C and FOXC2 in lung cancer patients. Our results indicated a functional link between resveratrol-mediated miRNA-520h regulation and tumor suppressing ability, and provide a new insight into the role of resveratrol-induced molecular and epigenetic regulations in tumor suppression.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Controlling the interaction between localized optical and mechanical excitations has recently become possible following advances in micro- and nanofabrication techniques. So far, most experimental ...studies of optomechanics have focused on measurement and control of the mechanical subsystem through its interaction with optics, and have led to the experimental demonstration of dynamical back-action cooling and optical rigidity of the mechanical system. Conversely, the optical response of these systems is also modified in the presence of mechanical interactions, leading to effects such as electromagnetically induced transparency (EIT) and parametric normal-mode splitting. In atomic systems, studies of slow and stopped light (applicable to modern optical networks and future quantum networks) have thrust EIT to the forefront of experimental study during the past two decades. Here we demonstrate EIT and tunable optical delays in a nanoscale optomechanical crystal, using the optomechanical nonlinearity to control the velocity of light by way of engineered photon-phonon interactions. Our device is fabricated by simply etching holes into a thin film of silicon. At low temperature (8.7 kelvin), we report an optically tunable delay of 50 nanoseconds with near-unity optical transparency, and superluminal light with a 1.4 microsecond signal advance. These results, while indicating significant progress towards an integrated quantum optomechanical memory, are also relevant to classical signal processing applications. Measurements at room temperature in the analogous regime of electromagnetically induced absorption show the utility of these chip-scale optomechanical systems for optical buffering, amplification, and filtering of microwave-over-optical signals.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Per and poly-fluoroalkyl substances (PFAS) have been recognized as contaminants of emerging concerns by the United States Environmental Protection Agency (US EPA) due to their environmental impact. ...Several advisory guidelines were proposed worldwide aimed at limiting their occurrences in the aquatic environments, especially for perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). This review paper aims to provide a holistic review in the emerging area of PFAS research by summarizing the spatiotemporal variations in PFAS concentrations in surface water systems globally, highlighting the possible trends of occurrences of PFAS, and presenting potential human health impacts as a result of PFAS exposure through surface water matrices. From the data analysis in this study, occurrences of PFOA and PFOS in many surface water matrices were observed to be several folds higher than the US EPA health advisory level of 70 ng/L for lifetime exposure from drinking water. Direct discharge and atmospheric deposition were identified as primary sources of PFAS in surface water and cryosphere, respectively. While global efforts focused on limiting usages of long-chain PFAS such as PFOS and PFOA, the practices of using short-chain PFAS such as perfluorobutanoic acid (PFBA) and perfluorobutane sulfonic acid (PFBS) and PFAS alternatives increased substantially. These compounds are also potentially associated with adverse impacts on human health, animals and biota.
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•Global shift in use of PFAS was observed from western to eastern part of the world.•Use of long-chain PFAS decreased due to regulations promoting short-chain PFAS.•Most studies reported PFOS and PFOA occurrences over US EPA threshold of 70 ng/L.•Discharge from WWTP acts as primary direct emission source of PFAS in rivers.•Globally high PFAS concentrations were observed in China, Japan, Korea, Australia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary Although low-grade gliomas (LGG) have a less aggressive course than do high-grade gliomas, the outcome of these tumours is ultimately fatal in most patients. Both the tumour and its treatment ...can cause disabling morbidity, particularly of cognitive functions. Because many patients present with seizures only, with no other signs and symptoms, maintenance of quality of life and function constitutes a particular challenge in LGG. The slow growth pattern of most LGG, and the rare radiological true responses despite a favourable clinical response to treatment, interferes with the use of progression-free survival as the primary endpoint in trials. Overall survival as an endpoint brings logistical challenges, and is sensitive to other non-investigational salvage therapies. Clinical trials for LGG need to consider other measures of patient benefit such as cognition, symptom burden, and seizure activity, to establish whether improved survival is reflected in prolonged wellbeing. This Review investigates clinical and imaging endpoints in trials of LGG, and provides response assessment in neuro-oncology (RANO) criteria for non-enhancing tumours. Additionally, other measures for patients with brain tumours that assess outcome are described. Similar considerations are relevant for trials of high-grade gliomas, although for these tumours survival is shorter and survival endpoints generally have more value than they do for LGG.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Evaluate the prevalence of meeting the updated 2018 Physical Activity Guidelines for Americans (150 unbouted minutes in moderate-to-vigorous intensity physical activity MVPA) and determine ...cross-sectional factors associated with Guideline attainment in a community-based cohort of adults with or at elevated risk for knee osteoarthritis (OA).
Physical activity was monitored for 1 week in a subset of Osteoarthritis Initiative (OAI) participants with or at increased risk for knee OA. Accelerometer-measured weekly MVPA minutes were calculated; sociodemographic (age, sex, race, education, and working status) and health-related (body mass index BMI, comorbidity, depressive symptoms, radiographic knee OA, and frequent knee symptoms) factors were assessed. We evaluated the prevalence of meeting 2018 Guidelines and used multivariate partial proportional odds model to identify factors associated with Guideline attainment, controlling for other factors in the model.
Among 1922 participants (age 65.1 standard deviation 9.1 years, BMI 28.4 4.8 kg/m2, 55.2% women), 44.1% men and 22.2% women met the 2018 PA Guidelines. Adjusted cross-sectional factors associated with not-meeting 2018 Guidelines were: women, older age, higher BMI, non-Whites, depressive symptoms, not working, and frequent knee symptoms.
In community-recruited adults with or at high risk for knee OA, more than 50% of men and nearly 80% of women failed to achieve the 2018 recommended level of at least 150 weekly unbouted minutes of MVPA. Study findings support gender and racial disparity in Guideline attainment and suggest addressing potentially modifiable factors (e.g., BMI, depressive symptoms, and frequent knee symptoms) to optimize benefits in PA-promoting interventions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Multiple sensor systems are designed by varying aza-crown ether moiety in silicon quantum dots (SiQDs) for detecting individual Mg2+, Ca2+, and Mn2+ metal ions with significant selectivity and ...sensitivity. The detection limit of Mg2+, Ca2+, and Mn2+ can reach 1.81, 3.15, and 0.47 μM, respectively. Upon excitation of the SiQDs which are coordinated with aza-crown ethers, the photoinduced electron transfer (PET) takes place from aza-crown ether moiety to the valence band of SiQDs core such that the reduced probability of electron–hole recombination may diminish the subsequent fluorescence. The fluorescence suppression caused by such PET effect will be relieved after selective metal ion is added. The charge-electron binding force between the metal ion and aza-crown ether hinders the PET and thereby restores the fluorescence of SiQDs. The design of sensor system is based on the fluorescence “turn-on” of SiQDs while in search of the appropriate metal ion. For practical application, the sensing capabilities of metal ions in the live cells are performed and the confocal image results reveal their promising applicability as an effective and nontoxic metal ion sensor.
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IJS, KILJ, NUK, PNG, UL, UM
Background and Purpose
The aim of this study was to determine the potency and molecular mechanism of action of YM155, a first‐in‐class survivin inhibitor that is currently under phase I/II clinical ...investigations, in various drug‐resistant breast cancers including the oestrogen receptor positive (ER+) tamoxifen‐resistant breast cancer and the caspase‐3‐deficient breast cancer.
Experimental Approach
The potency of YM155 in SK‐BR‐3, MDA‐MB‐231, MCF7 and its tamoxifen‐resistant sublines, TamR6, TamR7, TamR8, TamC3 and TamC6, were determined by MTT assay. Western blot analysis, flow cytometric analysis, reverse transcription‐PCR, fluorescent microscopy and comet assay were used to determine the molecular mechanism of action of YM155 in different breast cancer cell lines.
Key Results
YM155 was equally potent towards the parental ER+/caspase‐3‐deficient MCF7 breast cancer cells and its tamoxifen‐resistant sublines in vitro. The ER−/HER2+ SK‐BR‐3 breast cancer cells and the triple‐negative/caspase‐3‐expressing metastatic aggressive MDA‐MB‐231 breast cancer cells were also sensitive to YM155 with IC50 values in the low nanomolar range. Targeting survivin by YM155 modulated autophagy, induced autophagy‐dependent caspase‐7 activation and autophagy‐dependent DNA damage in breast cancer cells. Interestingly, YM155 also induced XIAP degradation and the degradation of XIAP might play an important role in YM155‐induced autophagy in breast cancer cells.
Conclusions and Implications
YM155 is a potent survivin inhibitor that has potential for the management of various breast cancer subtypes regardless of the expression of ER, HER2 and caspase‐3. Importantly, this study provides new insights into YM155's molecular mechanism of action and therapeutic potential in the treatment of tamoxifen‐resistant breast cancer.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND The importance of early intravenous (IV) antibiotic use for Mycobacterium abscessus complex lung diseases (MABC-LD) treatment remains unknown. METHODS A retrospective multi-centre
...observational study was conducted in Taiwan. Patients who were diagnosed with and received treatment for MABC-LD from January 2007 to April 2021 were included. Treatment outcome was defined as modified microbiological cure of MABC-LD. RESULTS Of
the 89 enrolled patients, 34 (38.2%) received IV antibiotics as part of the treatment regimen. The median time to IV initiation was 1 day (IQR 1-49); 24 (70.6%) of these patients received IV agents within 4 weeks, defined as early-use. Forty-two (47.2%) patients achieved modified microbiological
cure. In the multivariable logistic analysis, early IV antibiotic use was an independent factor associated with modified microbiological cure (aOR 5.32, 95% CI 1.66-17.00), whereas high radiological score (aOR 0.86, 95% CI 0.73-1.00) demonstrated negative association. CONCLUSIONS In
the present study, early use of effective IV antibiotic was prescribed in a low percentage (27%) for MABC-LD. By contrast, early IV antibiotic use was correlated with higher microbiological cure than were late or non-use. Future larger and prospective studies are needed to validate the association.
Objective
The G‐allele of the ‐1019C/G (rs6295) promoter polymorphism of the serotonin receptor 1A (HTR1A) gene has been implicated in anxiety; however, the underlying neurophysiological processes ...are still not fully understood. Recent evidence indicates that low parasympathetic (vagal) tone is predictive of anxiety. We thus conducted a structural equation model (SEM) to examine whether the HTR1A rs6295 variant can affect anxiety by altering parasympathetic nervous activity.
Method
A sample of 1141 drug‐free healthy Han Chinese was recruited for HTR1A genotyping. Autonomic nervous function was assessed by short‐term spectral analysis of heart rate variability (HRV). Anxiety and stress levels were evaluated by the Beck Anxiety Inventory (BAI) and the Perceived Stress Scale (PSS) respectively.
Results
The number of the HTR1A G allele was inversely correlated with high‐frequency power (HF), a parasympathetic index of HRV. The HF index was negatively associated with BAI scores. Furthermore, the good‐fitting SEM, adjusting for confounding variables (e.g., age and PSS levels), revealed a significant pathway linking rs6295 variant to BAI scores via HF index modulation.
Conclusion
These results are the first to show that HTR1A ‐1019C/G polymorphism influences anxiety levels by modulating parasympathetic tone, providing a neurophysiological insight into the role of HTR1A in human anxiety.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Objective Test the hypothesis that greater baseline peak external knee adduction moment (KAM), KAM impulse, and peak external knee flexion moment (KFM) during the stance phase of gait are ...associated with baseline-to-2-year medial tibiofemoral cartilage damage and bone marrow lesion progression, and cartilage thickness loss. Methods Participants all had knee OA in at least one knee. Baseline peak KAM, KAM impulse, and peak KFM (normalized to body weight and height) were captured and computed using a motion analysis system and six force plates. Participants underwent MRI of both knees at baseline and 2 years later. To assess the association between baseline moments and baseline-to-2-year semiquantitative cartilage damage and bone marrow lesion progression and quantitative cartilage thickness loss, we used logistic and linear regressions with generalized estimating equations (GEE), adjusting for gait speed, age, gender, disease severity, knee pain severity, and medication use. Results The sample consisted of 391 knees (204 persons): mean age 64.2 years (SD 10.0); BMI 28.4 kg/m2 (5.7); 156 (76.5%) women. Greater baseline peak KAM and KAM impulse were each associated with worsening of medial bone marrow lesions, but not cartilage damage. Higher baseline KAM impulse was associated with 2-year medial cartilage thickness loss assessed both as % loss and as a threshold of loss, whereas peak KAM was related only to % loss. There was no relationship between baseline peak KFM and any medial disease progression outcome measures. Conclusion Findings support targeting KAM parameters in an effort to delay medial OA disease progression.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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