A new two-dimensional, spiropyran-based polymer fluorescent nanoprobe with quantitative-fluorescent and photochromic properties for multi-substance detection.

One challenge of the structural design of a fluorescent probe is how to improve the detection performance on trace target analytes in complex samples. Herein a new polymer fluorescent nanoprobe (2DSP-C28) has been synthesized, by adopting a two-dimensional (2D), spiropyran (SP)-based nanosheet structure with hydrophobic long-chain alkanes (C28). Unlike a traditional SP-based small molecule probe, the 2DSP-C28probe can exhibit quantitative-fluorescent and photochromic properties. Under the detection of metal-ions, the nanoprobe in dimethyl sulfoxide aqueous solution is selectively fluorescent-quenched-responsive for Fe-ions (∼100µM), with a characteristic stoichiometric ratio of <10, a high sensitivity (limit of detection: ∼0.2µM). When the nanoprobe is incorporated into electrospun polyethylene oxide, it can be used for gas detection, and display a color-change with acid-base gas and identify the HF gas. It is expected that this new polymer fluorescent nanoprobe can be promisingly applied for rapidly environmental monitoring on the ion or gas pollution.

Programmable Retention Characteristics in MoS2-Based Atomristors for Neuromorphic and Reservoir Computing Systems.

In this study, we investigate the coexistence of short- and long-term memory effects owing to the programmable retention characteristics of a two-dimensional Au/MoS2/Au atomristor device and determine the impact of these effects on synaptic properties. This device is constructed using bilayer MoS2 in a crossbar structure. The presence of both short- and long-term memory characteristics is proposed by using a filament model within the bilayer transition-metal dichalcogenide. Short- and long-term properties are validated based on programmable multilevel retention tests. Moreover, we confirm various synaptic characteristics of the device, demonstrating its potential use as a synaptic device in a neuromorphic system. Excitatory postsynaptic current, paired-pulse facilitation, spike-rate-dependent plasticity, and spike-number-dependent plasticity synaptic applications are implemented by operating the device at a low-conductance level. Furthermore, long-term potentiation and depression exhibit symmetrical properties at high-conductance levels. Synaptic learning and forgetting characteristics are emulated using programmable retention properties and composite synaptic plasticity. The learning process of artificial neural networks is used to achieve high pattern recognition accuracy, thereby demonstrating the suitability of the use of the device in a neuromorphic system. Finally, the device is used as a physical reservoir with time-dependent inputs to realize reservoir computing by using short-term memory properties. Our study reveals that the proposed device can be applied in artificial intelligence-based computing applications by utilizing its programmable retention properties.

Geographic variation in breast reconstruction surgery after mastectomy for females with breast cancer in Alberta, Canada.

BACKGROUND: Breast cancer is the most common cancer affecting females in Canada, and about half of females with breast cancer are treated with mastectomy. We sought to evaluate geographic variation in breast reconstruction surgery in Alberta, Canada. METHODS: Using linked population-based administrative databases, we extracted data on all Alberta females aged 18 years and older who were diagnosed with breast cancer and treated with mastectomy during 2004-2017. Analyses included regression modelling of odds of reconstruction at 1 year and a spatial scan to identify geographic clusters of lower numbers of reconstruction. RESULTS: A total of 16 198 females diagnosed with breast cancer were treated with a mastectomy, and 1932 (11.9%) had reconstruction within 1 year postmastectomy. Those with reconstruction were more likely to be younger (adjusted odds ratio [OR] 16.7, 95% confidence interval [CI] 13.7-20.3; aged 21-44 yr v. ≥ 65 yr) and were less likely to be from lower-income neighbourhoods. They were more likely to have at least 1 comorbidity and were more likely to have advanced stages of cancer and to require chemotherapy (adjusted OR 0.55, 95% CI 0.47-0.65) or radiotherapy after mastectomy (adjusted OR 0.59, 95% CI 0.39-0.87) than females without reconstruction. We identified rural northern and southeastern clusters with frequencies of reconstruction that were 69.6% and 41.6% of what was expected, respectively. CONCLUSION: We found an overall postmastectomy rate of breast reconstruction of 11.9%, and we identified geographic variation. Predictors of reconstruction in Alberta were similar to those previously described in the literature, specifically with patients in rural communities having lower rates of reconstruction than their urban counterparts. These results suggest that further interventions are required to identify the specific barriers to reconstruction within rural communities and to create strategies to ensure equitable access to all residents.

CdS QDs grown on ellipsoidal BiVO4 for efficient photocatalytic degradation of tetracycline.

Designing efficient, inexpensive, and stable photocatalysts to degrade organic pollutants and antibiotics has become an effective way for environmental remediation. In this work, we successfully performed in situ growth of CdS QDs on the surface of elliptical BiVO4 to try to show the advantage of the binary heterojuncted photocatalyst (BVO@CdS) for the photocatalytic degradation of tetracycline (TC). The In situ growth of CdS QDs can provide a large number of reactive sites and also generate a larger contact area with BiVO4. In addition, compared with mechanical composite materials, in situ growth can significantly reduce the energy barrier at the interface between BiVO4 and CdS, providing more channels for the separation and migration of photogenerated charge carriers, and further improving reaction activity. As a result, BVO@CdS-0.05 shows the best degradation efficiency, with a degradation rate of 88% after 30 min under visible light. The TC photodegradation follows a pseudo-second-order reaction with a dynamic constant of 0.472 min-1, which is 6.47 times that of pure BiVO4, 7.24 times that of pure CdS QDs and 2 times that of the mechanical composite. The degradation rate of BVO@CdS-0.05 decreases to 77.8% with a retention rate of 88.5% after four cycles, demonstrating excellent stability. Through liquid chromatography-mass spectrometry (LC-MS) analysis, two possible pathways for TC degradation are proposed. Through free radical capture experiments, electron spin resonance measurements, and photoelectrochemical comprehensive analysis, it is confirmed that BVO@CdS composites have constructed an efficient Z-scheme heterojunction via in situ growth, thereby highly enhancing the separation and transport efficiency of charge carriers.

Betulin Accelerated the Functional Recovery of Injured Muscle in a Mouse Model of Muscle Contusion.

Muscle contusion is an injury to muscle fibers and connective tissues. It commonly happens in impact events, and could result in pain, swelling, and limited range of motion. Diclofenac is one of commonly used nonsteroidal anti-inflammatory drugs to alleviate pain and inflammation after injury. However, it can potentially cause some side effects including gastrointestinal complications and allergy. Betulin is a lupine-type pentacyclic triterpenoid. It is showed to have valuable pharmacological effects, but the physiological effect of betulin on muscle contusion has not been reported. This study aimed to explore the therapeutic effects of betulin on muscle contusion that produced by the drop-mass method in mice. C57BL/6 mice were randomly assigned to control (no injury), only drop-mass injury (Injury), diclofenac treatment (Injury+diclofenac), and betulin treatment (Injury+betulin) groups. Injury was executed on the gastrocnemius of the right hind limb, and then phosphate-buffered saline (PBS), diclofenac, or betulin were oral gavage administrated respectively for 7 days. Results revealed that betulin significantly restored motor functions based on locomotor activity assessments, rota-rod test, and footprints analysis. Betulin also attenuated serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels after muscle injury. Neutrophil infiltration was alleviated and desmin levels were increased after betulin treatment. Our data demonstrated that betulin attenuated muscle damage, alleviated inflammatory response, improved muscle regeneration, and restored motor functions after muscle contusion. Altogether, betulin may be a potential compound to accelerate the repair of injured muscle.

Berberine inhibits Candida albicans growth by disrupting mitochondrial function through the reduction of iron absorption.

AIMS: This study aimed to investigate whether berberine (BBR) can inhibit the iron reduction mechanism of Candida albicans, lowering the iron uptake of the yeast and perhaps having antimicrobial effects. METHODS AND RESULTS: We determined that BBR may cause extensive transcriptional remodeling in C. albicans and that iron permease Ftr1 played a crucial role in this process through eukaryotic transcriptome sequencing. Mechanistic research showed that BBR might selectively inhibit the iron reduction pathway to lower the uptake of exogenous iron ions, inhibiting C. albicans from growing and metabolizing. Subsequent research revealed that BBR caused significant mitochondrial dysfunction, which triggered the process of mitochondrial autophagy. Moreover, we discovered that C. albicans redox homeostasis, susceptibility to antifungal drugs, and hyphal growth are all impacted by the suppression of this mechanism by BBR. CONCLUSIONS: The iron reduction mechanism in C. albicans is disrupted by BBR, which disrupts mitochondrial function and inhibits fungal growth. These findings highlight the potential promise of BBR in antifungal applications.

Thiol-ene chemistry incorporates a new spiropyran-containing polyurethane ionogel with photochromic, photomechanical and photoconductive properties.

The photocuring technology based on thiol-ene click reaction can be easily applied for copolymerizing or crosslinking the acrylate monomers for ionogels. However, there is still a problem: when the acrylate monomers contain the popular spiropyran as the stimuli-responsive group, it should be concerned about the participation of the active CC bond from the ring-opened spiropyran during a thiol-ene reaction, which may in turn affect the stimuli-responsiveness of the spiropyran. Up to now, the structure and properties of spiropyran-containing ionogels in this case have still not been well investigated. Therefore, in this work we carefully study a new spiropyran-containing polyurethane ionogel by crosslinking an acrylate-terminated, spiropyran-containing polyurethane prepolymer and a polythiol in ionic liquid through thiol-ene chemistry. It is found for the first time that, during constructing an ionogel, the coexistence of a reversible thiol-ene reaction between the CC bond from the ring-opened spiropyran and the thiol group can bring about a different reverse photochromic behavior. The proposed mechanism of the abnormal photochromism is analyzed. In addition, it is also observed that the thiol-ene chemistry can incorporate photomechanical and photoconductive properties into the new spiropyran-containing ionogel.

Resonance-Enhanced Emission Effects toward Dual-State Emissive Bright Red and Near-Infrared Emitters.

Resonance-enhanced emission (REE) effect was discovered and lead to a novel dye family of hydrostyryl pyridinium derivatives in our recent work. Herein, the REE effect was employed to design a red and near-infrared dual-state emissive fluorophore family of SW-OH-NO2 derivatives which were easily synthesized by coupling an electron-withdrawing group (W) onto nitro(hydroxyl)styryl (S-OH-NO2 ) through a C=C double bond as π-bridge. The deprotonation of a phenolic hydroxyl group promoted by a nitro group and the electron-withdrawing group (W) on the other side of the π-bridge triggered resonance, resulting in significantly red-shifted emission. All the resultant SW-OH-NO2 compounds showed excellent dual-state emission behavior. Remarkably, hydrostyryl quinolinium (SQ-OH-NO2 ) is one of the smallest NIR emitter molecular skeleton (λem =725 nm, MW<400) and showed dual-state emission characteristics and obvious viscosity-depended fluorescent behaviors. In addition to constructing electron donor-acceptor structures and prolonging π-bridges, the REE effect promises a reliable strategy toward novel fluorophores with small size, long emissive wavelength, and dual-emission characteristics, and importantly, feasible industrial manufactures and applications due to their easy and low-cost synthesis strategy.

Emergency department crowding negatively influences outcomes for adults presenting for chronic obstructive pulmonary disease.

OBJECTIVES: Emergency department (ED) crowding leads to poor outcomes. Patients with respiratory conditions like chronic obstructive pulmonary disease (COPD) are especially vulnerable to crowding-related delays in care. We aimed to assess the associations of ED crowding metrics with outcomes for patients presenting with COPD. METHODS: We conducted a population-based cohort study of adult patients presenting with a diagnosis of COPD to 18 high-volume EDs between 2014 and 2019 in Alberta, Canada. Administrative databases provided date and time data on key stages of the presentation including physician initial assessment and disposition decision. Crowding metrics were calculated using facility-specific median physician initial assessment and length of stay. Patient presentations were grouped by acuity and mixed-effects regression models were fit to adjust for the clustering at the facility level. RESULTS: There were 49,085 presentations for COPD made by 25,734 patients (median age = 73 years). A 1-h increase in the physician initial assessment metric was associated with an increase in physician initial assessment for COPD patients by 23, 53, and 59 min for the high, moderate, and low acuity groups, respectively, adjusted for other predictors. For the low acuity group, this metric was associated with an increased length of stay of 73 min for admitted individuals. Similarly, an increase in the length of stay metric was also associated with an increased likelihood of being admitted for all acuity groups. CONCLUSIONS: For patients with COPD, ED crowding results in delays in assessment increased length of stay, and increased proportion of patients admitted. These results suggest that ED crowding mitigation efforts to provide timely care for patients with COPD are urgently needed. TRIAL REGISTRATION: N/A.

RéSUMé: OBJECTIFS: L'encombrement des services d'urgence entraîne de mauvais résultats. Les patients souffrant de maladies respiratoires telles que la maladie pulmonaire obstructive chronique (MPOC) sont particulièrement vulnérables aux retards de soins liés à l'encombrement. Notre avons cherché à évaluer les associations entre les paramètres d'encombrement des services d'urgence et les résultats pour les patients présentant une MPOC. MéTHODES: Nous avons mené une étude de cohorte basée sur la population de patients adultes se présentant avec un diagnostic de MPOC dans dix-huit services d'urgence à haut volume entre 2014 et 2019 en Alberta, au Canada. Les bases de données administratives ont fourni des données sur la date et l'heure des principales étapes de la présentation, y compris l'évaluation initiale par le médecin et la décision de sortie. Les mesures d'encombrement ont été calculées à partir de l'évaluation initiale médiane du médecin et de la durée du séjour propres à l'établissement. Les présentations des patients ont été regroupées par gravité et des modèles de régression à effets mixtes ont été ajustés pour tenir compte du regroupement au niveau de l'établissement. RéSULTATS: Il y a eu 49 085 présentations pour la MPOC effectuées par 25 734 patients (âge médian = 73 ans). Une augmentation d'une heure de l'évaluation initiale par le médecin était associée à une augmentation de l'évaluation initiale par le médecin pour les patients atteints de MPOC de 23, 53 et 59 min pour les groupes de gravité élevée, modérée et faible, respectivement, après ajustement pour d'autres facteurs prédictifs. Pour le groupe de faible gravité, ce paramètre était associé à une augmentation de la durée de séjour de 73 min pour les personnes admises. De même, une augmentation de la durée du séjour était également associée à une probabilité accrue d'admission pour tous les groupes de gravité. CONCLUSIONS: Pour les patients atteints de MPOC, l'encombrement des urgences entraîne des retards dans l'évaluation, une augmentation de la durée du séjour et une augmentation de la proportion de patients admis. Ces résultats suggèrent qu'il est urgent d'atténuer l'encombrement des urgences afin de fournir des soins en temps opportun aux patients atteints de MPOC. ENREGISTREMENT DE L'ESSAI: N/A.

Attenuation of Endoplasmic Reticulum Stress Enhances Carvacrol-Induced Apoptosis in Osteosarcoma Cell Lines.

Carvacrol is a monoterpenoid phenol that has excellent antimicrobial, antiviral, and anti-inflammatory activities. It can also improve wound healing. However, few studies have explored its antitumor effect on osteosarcoma. In this report, we tried to determine the potential efficacy of carvacrol against osteosarcoma cell lines. Our data revealed that carvacrol exposure inhibited the proliferation of osteosarcoma HOS and U-2 OS cells. In addition, carvacrol exposure enhanced the levels of cleaved PARP and caspase 3 and increased annexin V-positive cells, indicating that carvacrol exposure triggers apoptosis in osteosarcoma cell lines. Furthermore, the levels of reactive oxygen species (ROS) were enhanced after carvacrol exposure and cotreatment with NAC, the ROS scavenger, decreased the levels of cleaved PARP and caspase 3, suggesting the involvement of ROS in carvacrol-induced apoptosis. Importantly, we found that carvacrol exposure triggered several protein expressions related to endoplasmic reticulum (ER) stress, including GRP78/Bip, IRE1a, PERK, and CHOP, in HOS and U-2 OS cells, indicating that carvacrol exposure could result in ER stress in these cell lines. Cotreatment with the ER stress inhibitor 4-PBA increased the levels of cleaved PARP and caspase 3 and further suppressed cellular proliferation in carvacrol-exposed osteosarcoma cell lines. Overall, the results indicate that induced ER stress can protect cells from apoptosis, but increased ROS contributes to apoptosis in carvacrol-treated cells. In this report, we first demonstrate the role of ER stress in carvacrol-induced apoptosis and suggest that ER stress could be targeted to enhance the antitumor activity of carvacrol in osteosarcoma cell lines.

The three-dimensionally ordered microporous CaTiO3 coupling Zn0.3Cd0.7S quantum dots for simultaneously enhanced photocatalytic H2 production and glucose conversion.

Glucose conversion assisted photocatalytic water splitting technology to simultaneously produce H2 and high value-added chemicals is a promising method for alleviating the energy shortage and environmental crisis. In this work, we constructing type II heterojunction by in-situ coupling Zn0.3Cd0.7S quantum dots (ZCS QDs) on three-dimensionally ordered microporous CaTiO3 (3DOM CTO) for photocatalytic H2 production and glucose conversion. The DFT calculations demonstrate that substitution of Zn on the Cd site improves the separation and transmission of photogenerated carriers. Therefore, 3DOM CTO-ZCS composite exhibits best H2 production performance (2.81 mmol g-1h-1) and highest apparent quantum efficiency (AQY) (5.56 %) at 365 nm, which are about 47 and 18 times that of CTO nanoparticles (NPs). The improved catalytic performance ascribed to not only good mass diffusion and exchange, highly efficient light harvesting of 3DOM structure, but also the efficient charges separation of type Ⅱ heterojunction. The investigation on photocatalytic mechanism indicates that the glucose is mainly converted to gluconic acid and lactic acid, and the control reaction step is gluconic acid to lactic acid. The selectivity for gluconic acid on 3DOM CTO-ZCS is 85.65 %. Our work here proposes a green sustainable method to achieve highly efficient H2 production and selective conversion of glucose to gluconic acid.

Acute generation of reactive oxygen species that induced by doxycycline pretreatment results in rapid cell death in polyphyllin G-treated osteosarcoma cell lines.

Polyphyllin G, a pennogenyl saponin extracted from Paris polyphylla, has been shown to possess antitumor effects. In this study, we demonstrated that doxycycline, an antibiotic medicine, could significantly enhance the sensitivities of osteosarcoma cell lines to polyphyllin G. As the cells were pretreated with doxycycline at non-toxic concentrations and then co-exposed to polyphyllin G, this combination could induce a rapid cell death distinct from apoptosis. The non-apoptotic cell death was characterized by a loss of integrity of plasma membrane without externalization of phosphatidyl serine. Furthermore, this combined treatment resulted in suppression of cell viability and colony-forming ability, and increased the level of γ-H2A.X, a critical marker for DNA damage, in osteosarcoma cell lines. When examining the underlying mechanism, it was revealed combination of polyphyllin G and doxycycline triggered an enhanced generation of reactive oxygen species (ROS), and up-regulated mitochondrial oxidative stress within 0.5 h. Co-administration of the ROS inhibitor NAC reversed the suppressed cell viability and colony-forming ability, and abolished the increased level of γ-H2A.X in the cells with the combined treatment, indicating that the enhanced ROS was involved in the anti-proliferative effect of the combined treatment. Overall, the results demonstrated that doxycycline may function as chemosensitizers by inducing an acute and lethal ROS production to enhance cytotoxic of polyphyllin G in osteosarcoma cell lines, and the combined use of drugs may provide an alternative thinking for the development of new therapeutic agents.

Emergency department crowding negatively influences outcomes for adults presenting with asthma: a population-based retrospective cohort study.

BACKGROUND: Access to emergency department (ED) services is important for patients with acute asthma; however, ED crowding may impact the quality of care and compromise outcomes. We examine the association between ED crowding metrics and individual patient outcomes for adults presenting with asthma. METHODS: This population-based retrospective cohort study extracted all ED presentations made by patients aged 18 to 55 years to 18 high-volume EDs in Alberta from April 2014 to March 2019. Physician initial assessment (PIA) time and ED length of stay (LOS) for discharged and admitted patients were calculated. Other metrics and patient outcomes were also obtained. Linear and generalized linear models were fit for continuous and categorical outcomes. Cox proportional hazards models were used for time-to-event outcomes. RESULTS: There were 17,724 ED presentations by 12,569 adults. The median age was 33 years, and females (58.7%) made more presentations. ED crowding affected the PIA time for all triage groups. For the high acuity group (Canadian Triage and Acuity Scale [CTAS] 1/2), 1 h increase in median facility-specific PIA was associated with 26 min (95%CI: 24,28) increase; for the moderate acuity (CTAS 3) and low acuity (CTAS 4/5) groups, the individual-level PIA increased by 54 min (95%CI: 53,55) and 61 min (95%CI: 59,63), respectively adjusted by other predictors. Increases in facility PIA resulted in increase in odds of admissions for the high acuity group and increase odds of left without completion of care for the moderate and low acuity groups. CONCLUSION: The care provided for patients from all triage groups was impacted when EDs experienced crowding. Effective interventions are needed to mitigate ED crowding and improve care and outcomes for this important patient group.

Different Cell Responses to Hinokitiol Treatment Result in Senescence or Apoptosis in Human Osteosarcoma Cell Lines.

Hinokitiol is a tropolone-related compound isolated from the heartwood of cupressaceous plants. It is known to exhibit various biological functions including antibacterial, antifungal, and antioxidant activities. In the study, we investigated the antitumor activities of hinokitiol against human osteosarcoma cells. The results revealed that hinokitiol treatment inhibited cell viability of human osteosarcoma U-2 OS and MG-63 cells in the MTT assay. Further study revealed that hinokitiol exposure caused cell cycle arrest at the S phase and a DNA damage response with the induction of γ-H2AX foci in both osteosarcoma cell lines. In U-2 OS cells with wild-type tumor suppressor p53, we found that hinokitiol exposure induced p53 expression and cellular senescence, and knockdown of p53 suppressed the senescence. However, in MG-63 cells with mutated p53, a high percentage of cells underwent apoptosis with cleaved-PARP expression and Annexin V staining after hinokitiol treatment. In addition, up-regulated autophagy was observed both in hinokitiol-exposed U-2 OS and MG-63 cells. As the autophagy was suppressed through the autophagy inhibitor chloroquine, hinokitiol-induced senescence in U-2 OS cells was significantly enhanced accompanying more abundant p53 expression. In MG-63 cells, co-treatment of chloroquine increased hinokitiol-induced apoptosis and decreased cell viability of the treated cells. Our data revealed that hinokitiol treatment could result in different cell responses, senescence or apoptosis in osteosarcoma cell lines, and suppression of autophagy could promote these effects. We hypothesize that the analysis of p53 status and co-administration of autophagy inhibitors might provide more precise and efficacious therapies in hinokitiol-related trials for treating osteosarcoma.

Template-Free Construction of Tin Oxide Porous Hollow Microspheres for Room-Temperature Gas Sensors.

Porous hollow microsphere (PHM) materials represent ideal building blocks for realizing diverse functional applications such as catalysis, energy storage, drug delivery, and chemical sensing. This has stimulated intense efforts to construct metal oxide PHMs for achieving highly sensitive and low-power-consumption semiconductor gas sensors. Conventional methods for constructing PHMs rely on delicate reprogramming of templates and may suffer from the structural collapse issue during the removal of templates. Here, we propose a template-free method for the construction of tin oxide (SnO2) PHMs via the competition between the solvent evaporation rate and the phase separation dynamics of colloidal SnO2 quantum wires. The SnO2 PHMs (typically 3 ± 0.5 µm diameter and approximately 200 nm shell thickness) exhibit desirable structural stability with desirable processing compatibility with various substrates. This enables the realization of NO2 gas sensors having a superior response and recovery process at room temperature. The superior NO2-sensing characteristic is attributed to the effective gas adsorption competition on solid surfaces benefiting from efficient diffusion channels, enhancing the interaction of metal oxide solids with gas molecules in terms of the receptor function, transducer function, and utility factor. In addition, the one-step deposition of SnO2 PHMs directly onto device substrates simplifies the fabrication conditions for semiconductor gas sensors. The desirable structural stability of PHMs combined with the functional diversity of metal oxides may open new opportunities for the design of functional materials and devices.

Butein induces cellular senescence through reactive oxygen species-mediated p53 activation in osteosarcoma U-2 OS cells.

Butein is a flavonoid isolated from various medicinal plants. It is known to have different biological activities including anti-inflammation, anti-adipogenesis, and anti-angiogenesis. In the study, we demonstrated the anti-proliferative effect of butein in human osteosarcoma U-2 OS cells. Our data showed that butein significantly suppressed the viability and colony formation ability of U-2 OS cells. Further experiments revealed butein exposure resulted in a cell cycle arrest at S and G2/M phase in U-2 OS cells. Importantly, we found that butein activated the tumor suppressor p53, and trigged a p53-dependent senescence in U-2 OS cells. Knockdown of p53 suppressed the senescence and rescued the viability in butein-treated U-2 OS cells. Furthermore, we observed that butein exposure significantly enhanced reactive oxygen species (ROS) levels in U-2 OS cells. Co-administration of the ROS inhibitor NAC largely abolished the up-regulated p53 protein level, and rescued the suppressed viability and colony formation ability in butein-exposed U-2 OS cells. Taken together, our data proposed the increased ROS by butein exposure activated p53, and the activated p53 was involved in the anti-proliferative effect of butein via inducing senescence in U-2 OS cells. This report suggests that butein is a promising candidate for cancer therapy against osteosarcoma.

Betulin inhibits mTOR and induces autophagy to promote apoptosis in human osteosarcoma cell lines.

Betulin is a lupane type pentacyclic triterpenoid, and commonly found in the bark of birch trees. It displays various pharmacological properties, such as antibacterial, anti-inflammation, antitumor, and antiviral. In this report, we attempted to investigate the anti-proliferative and pro-apoptotic effects of betulin on osteosarcoma cell lines. Our results revealed that betulin significantly decreased cell viability and colony formation in osteosarcoma cell lines. Dose-dependent induction of Annexin V positive cells, activated caspase 8, activated caspase 9, activated caspase 3, and the cleavage of poly (ADP-ribose) polymerase were observed after the treatment with betulin, indicating betulin induces apoptosis in osteosarcoma cell lines. mTOR has been identified as a key modulator of autophagy in response to different stresses. In this study, we found that the treatment with betulin suppressed the activation of mTOR, and increased the level of LC 3-II, the autophagy marker, in osteosarcoma cell lines. Co-administration of the autophagy inhibitor chloroquine significantly rescued the cell viability and the clonogenic activity in betulin-treated osteosarcoma cell lines. Our data showed that betulin induced autophagy, and the up-regulated autophagy positively contributed to the apoptosis. Taken together, our findings suggested that betulin may serve as a promising anti-proliferative agent for treating osteosarcoma.

Resistance state evolution under constant electric stress on a MoS2 non-volatile resistive switching device.

MoS2 has been reported to exhibit a resistive switching phenomenon in a vertical metal-insulator-metal (MIM) structure and has attracted much attention due to its ultra-thin active layer thickness. Here, the resistance evolutions in the high resistance state (HRS) and low resistance state (LRS) are investigated under constant voltage stress (CVS) or constant current stress (CCS) on MoS2 resistive switching devices. Interestingly, compared with bulk transition metal oxides (TMO), MoS2 exhibits an opposite characteristic in the fresh or pre-RESET device in the "HRS" wherein the resistance will increase to an even higher resistance after applying CVS, a unique phenomenon only accessible in 2D-based resistive switching devices. It is inferred that instead of in the highest resistance state, the fresh or pre-RESET devices are in an intermediate state with a small amount of Au embedded in the MoS2 film. Inspired by the capability of both bipolar and unipolar operation, positive and negative CVS measurements are performed and show similar characteristics. In addition, it is observed that the resistance state transition is faster when using higher electric stress. Numerical simulations have been performed to study the temperature effect with small-area integration capability. These results can be explained by a modified conductive-bridge-like model based on Au migration, uncovering the switching mechanisms in the ultrathin 2D materials and inspiring future studies in this area.

Licochalcone A Suppresses the Proliferation of Osteosarcoma Cells through Autophagy and ATM-Chk2 Activation.

Licochalcone A, a flavonoid extracted from licorice root, has been shown to exhibit broad anti-inflammatory, anti-bacterial, anticancer, and antioxidative bioactivity. In this study, we investigated the antitumor activity of Licochalcone A against human osteosarcoma cell lines. The data showed that Licochalcone A significantly suppressed cell viability in MTT assay and colony formation assay in osteosarcoma cell lines. Exposure to Licochalcone A blocked cell cycle progression at the G2/M transition and induced extrinsic apoptotic pathway in osteosarcoma cell lines. Furthermore, we found the Licochalcone A exposure resulted in rapid ATM and Chk2 activation, and high levels of nuclear foci of phosphorylated Chk2 at Thr 68 site in osteosarcoma cell lines. In addition, Licochalcone A exposure significantly induced autophagy in osteosarcoma cell lines. When Licochalcone A-induced autophagy was blocked by the autophagy inhibitor chloroquine, the expression of activated caspase-3 and Annexin V positive cells were reduced, and cell viability was rescued in Licochalcone A-treated osteosarcoma cell lines. These data indicate that the activation of ATM-Chk2 checkpoint pathway and autophagy may contribute to Licochalcone A-induced anti-proliferating effect in osteosarcoma cell lines. Our findings display the possibility that Licochalcone A may serve as a potential therapeutic agent against osteosarcoma.

DAAM1-mediated migration and invasion of ovarian cancer cells are suppressed by miR-208a-5p.

Ovarian cancer (OvCa) has the highest morbidity among all gynecologic cancers worldwide, and its distant metastasis is one of main causes for the poor prognosis of OvCa patients. Our previous studies have reported that DAAM1-involved signaling pathways play vital roles in metastasis of breast cancer. However, whether DAAM1 participates in OvCa migration and/or invasion is still unknown. The impact of DAAM1 on cell migration and invasion in OvCa was evaluated by wound healing assay and Boyden chamber assay. The specific miRNA targeting DAAM1 was predicted by bioinformatics methods and verified by dual-luciferase activity assay. The miR-208a-5p expression levels in OvCa tissues and the impacts of miR-208a-5p on cell migration and invasion were also assessed, respectively. High expression of DAAM1 was associated with distant metastasis in OvCa. Silence of DAAM1 by siRNA blocked the migration and invasion of OVCAR-3 cells. MiR-208a-5p directly targeted DAAM1 and was shown a decreased expression in metastatic OvCa tissues. Elevated expression of miR-208a-5p inhibited the migration and invasion of OVCAR-3 cell which can be rescued by DAAM1 overexpression. Our data suggest that miR-208-5p/DAAM1 axis participates in OvCa migration and invasion and may be a novel clinical target to limit OvCa metastasis.