Resveratrol, a naturally occurring phytopolyphenol compound, has attracted extensive interest in recent years because of its diverse pharmacological characteristics. Although resveratrol possesses ...chemopreventive properties against several cancers, the molecular mechanisms by which it inhibits cell growth and induces apoptosis have not been clearly understood. The present study was carried out to examine whether PI3K/AKT/FOXO pathway mediates the biological effects of resveratrol.
Resveratrol inhibited the phosphorylation of PI3K, AKT and mTOR. Resveratrol, PI3K inhibitors (LY294002 and Wortmannin) and AKT inhibitor alone slightly induced apoptosis in LNCaP cells. These inhibitors further enhanced the apoptosis-inducing potential of resveratrol. Overexpression of wild-type PTEN slightly induced apoptosis. Wild type PTEN and PTEN-G129E enhanced resveratrol-induced apoptosis, whereas PTEN-G129R had no effect on proapoptotic effects of resveratrol. Furthermore, apoptosis-inducing potential of resveratrol was enhanced by dominant negative AKT, and inhibited by wild-type AKT and constitutively active AKT. Resveratrol has no effect on the expression of FKHR, FKHRL1 and AFX genes. The inhibition of FOXO phosphorylation by resveratrol resulted in its nuclear translocation, DNA binding and transcriptional activity. The inhibition of PI3K/AKT pathway induced FOXO transcriptional activity resulting in induction of Bim, TRAIL, p27/KIP1, DR4 and DR5, and inhibition of cyclin D1. Similarly, resveratrol-induced FOXO transcriptional activity was further enhanced when activation of PI3K/AKT pathway was blocked. Over-expression of phosphorylation deficient mutants of FOXO proteins (FOXO1-TM, FOXO3A-TM and FOXO4-TM) induced FOXO transcriptional activity, which was further enhanced by resveratrol. Inhibition of FOXO transcription factors by shRNA blocked resveratrol-induced upregulation of Bim, TRAIL, DR4, DR5, p27/KIP1 and apoptosis, and inhibition of cyclin D1 by resveratrol.
These data suggest that FOXO transcription factors mediate anti-proliferative and pro-apoptotic effects of resveratrol, in part due to activation of extrinsic apoptosis pathway.
We present a restricted infection rate inverse binomial-based approach to better predict COVID-19 cases after a family gathering. The traditional inverse binomial (IB) model is inappropriate to match ...the reality of COVID-19, because the collected data contradicts the model’s requirement that variance should be larger than the expected value. Our version of an IB model is more appropriate, as it can accommodate all potential data scenarios in which the variance is smaller, equal, or larger than the mean. This is unlike the usual IB, which accommodates only the scenario in which the variance is more than the mean. Therefore, we propose a refined version of an IB model to be able to accommodate all potential data scenarios. The application of the approach is based on a restricted infectivity rate and methodology on COVID-19 data, which exhibit two clusters of infectivity. Cluster 1 has a smaller number of primary cases and exhibits larger variance than the expected cases with a negative correlation of 28%, implying that the number of secondary cases is lesser when the number of primary cases increases and vice versa. The traditional IB model is appropriate for Cluster 1. The probability of contracting COVID-19 is estimated to be 0.13 among the primary, but is 0.75 among the secondary in Cluster 1, with a wider gap. Cluster 2, with a larger number of primary cases, exhibits smaller variance than the expected cases with a correlation of 79%, implying that the number of primary and secondary cases do increase or decrease together. Cluster 2 disqualifies the traditional IB model and requires its refined version. The probability of contracting COVID-19 is estimated to be 0.74 among the primary, but is 0.72 among the secondary in Cluster 2, with a narrower gap. The advantages of the proposed approach include the model’s ability to estimate the community’s health system memory, as future policies might reduce COVID’s spread. In our approach, the current hazard level to be infected with COVID-19 and the odds of not contracting COVID-19 among the primary in comparison to the secondary groups are estimable and interpretable.
Resveratrol (3, 4', 5 tri-hydroxystilbene), a naturally occurring polyphenol, exhibits anti-inflammatory, antioxidant, cardioprotective and antitumor activities. We have recently shown that ...resveratrol can enhance the apoptosis-inducing potential of TRAIL in prostate cancer cells through multiple mechanisms in vitro. Therefore, the present study was designed to validate whether resveratrol can enhance the apoptosis-inducing potential of TRAIL in a xenograft model of prostate cancer.
Resveratrol and TRAIL alone inhibited growth of PC-3 xenografts in nude mice by inhibiting tumor cell proliferation (PCNA and Ki67 staining) and inducing apoptosis (TUNEL staining). The combination of resveratrol and TRAIL was more effective in inhibiting tumor growth than single agent alone. In xenografted tumors, resveratrol upregulated the expressions of TRAIL-R1/DR4, TRAIL-R2/DR5, Bax and p27(/KIP1), and inhibited the expression of Bcl-2 and cyclin D1. Treatment of mice with resveratrol and TRAIL alone inhibited angiogenesis (as demonstrated by reduced number of blood vessels, and VEGF and VEGFR2 positive cells) and markers of metastasis (MMP-2 and MMP-9). The combination of resveratrol with TRAIL further inhibited number of blood vessels in tumors, and circulating endothelial growth factor receptor 2-positive endothelial cells than single agent alone. Furthermore, resveratrol inhibited the cytoplasmic phosphorylation of FKHRL1 resulting in its enhanced activation as demonstrated by increased DNA binding activity.
These data suggest that resveratrol can enhance the apoptosis-inducing potential of TRAIL by activating FKHRL1 and its target genes. The ability of resveratrol to inhibit tumor growth, metastasis and angiogenesis, and enhance the therapeutic potential of TRAIL suggests that resveratrol alone or in combination with TRAIL can be used for the management of prostate cancer.
Learning 3D mesh segmentation and labeling Kalogerakis, Evangelos; Hertzmann, Aaron; Singh, Karan
ACM transactions on graphics,
07/2010, Letnik:
29, Številka:
4
Journal Article
Recenzirano
Odprti dostop
This paper presents a data-driven approach to simultaneous segmentation and labeling of parts in 3D meshes. An objective function is formulated as a Conditional Random Field model, with terms ...assessing the consistency of faces with labels, and terms between labels of neighboring faces. The objective function is learned from a collection of labeled training meshes. The algorithm uses hundreds of geometric and contextual label features and learns different types of segmentations for different tasks, without requiring manual parameter tuning. Our algorithm achieves a significant improvement in results over the state-of-the-art when evaluated on the Princeton Segmentation Benchmark, often producing segmentations and labelings comparable to those produced by humans.
Microgrids face significant challenges due to the unpredictability of distributed generation (DG) technologies and fluctuating load demands. These challenges result in complex power management ...systems characterised by voltage/frequency variations and intricate interactions with the utility grid. Model predictive control (MPC) has emerged as a powerful technique to effectively address these challenges. By applying a receding horizon control strategy, MPC offers promising solutions for optimising constraints and enhancing microgrid operations. The purpose of this review paper is to comprehensively analyse the application of MPC in microgrids, covering various levels of the hierarchical control structure. Furthermore, this paper explores the emerging trend of employing MPC across microgrid applications, ranging from converter control levels for power quality to overarching energy management systems. It also investigates the future research perspectives by considering the challenges associated with establishing MPC-based microgrid control. The key conclusion derived from this review paper is that the implementation of MPC techniques in microgrid operations can greatly improve their overall performance, efficiency, and resilience. This paper thoroughly examines the various challenges faced in MPC-based microgrid operations, underscoring the significance of conducting research in advanced artificial intelligence (AI)-based MPC methods. It highlights how these cutting-edge AI techniques can bring about economic benefits in microgrid operations, addressing the complex demands of efficient energy management in a rapidly evolving landscape. The presented insights strive to enhance the comprehension and adoption of MPC techniques in microgrid settings, actively contributing to the ongoing improvement of their operational processes. By shedding light on key aspects and offering valuable guidance, this work aims to propel the advancement and effective utilisation of MPC methodologies in microgrids, ultimately leading to optimised performance and enhanced overall operations.
Nanocomposite materials are potentially revolutionizing many technologies, including sensors. In this paper, we described the application of “PANI/MWCNTs/Starch” modified carbon paste electrode ...(PCS-CPE) as a simple and highly sensitive cholesterol sensor. This novel nano-composite material has integrated nano-morphology, where polyaniline could interact effectively with the additives; pi-pi stacking “MWCNTs,” and covalently bonded with starch. Specific binding sites (sugar chains), better electro-catalytic properties and fast electron transfer facilitated the oxidation of cholesterol. Fourier transform infrared spectra confirmed the interaction of cholesterol with the composite material. The sensing response of PCS was measured by cyclic voltammetry and chronoamperometry (0.1 M PBS-5 used as supporting electrolyte). As the amount of cholesterol increased in the test solution, cyclic voltammograms showed a rise of peak current (cathodic and anodic). Under the normal experimental conditions, the developed sensor exhibited wide linear dynamic range (0.032 to 5 mM) (upper limit is due to lack of solubility of cholesterol), high sensitivity (800 μAmM
−1
cm
−2
), low detection limit (0.01 mM) and shorter response time (within 4–6 s). Analytical specificity, selectivity, and sensitivity during cholesterol estimation were compared with the response of some other analytes (ascorbic acid, glucose, l-dopa, urea and lactic acid). This novel sensor was successfully applied to estimate cholesterol in cow milk (used as a model real sample). The sensing platform is highly sensitive and shows a linear response towards cholesterol without using any additional redox mediator or enzyme, thus this material is extremely promising for the realization of a low-cost integrated cholesterol sensor device.
Graphical abstract
Cyclic voltammetric response of cholesterol of composite modified carbon paste capillary electrode
Literature presents limited information on histological subtypes and their association with other factors influencing the survival of melanoma patients. To explore the risk of death due to melanoma ...associated with histological subtypes, this retrospective study used the Surveillance, Epidemiology, and End Results program (SEER) data from 1998 to 2019.
A total of 27,532 patients consisting of 15,527 males and 12,005 females. The Hypertabastic Accelerated Failure Time model was used to analyze the impact of histology on the survival of patients with cutaneous or mucosal melanoma.
The median survival time (MST) for cutaneous patients was 149 months, whereas those diagnosed with mucosal melanoma was 34 months. Nodular melanoma had a hazard ratio of 3.40 95% CI: (2.94, 3.94) compared to lentigo maligna melanoma. Across all histological subtypes, females had a longer MST, when compared to males. The hazard ratio (HR) of distant to localized melanoma was 9.56 95% CI: (7.58, 12.07).
Knowledge of patients' histological subtypes and their hazard assessment would enable clinicians and healthcare providers to perform personalized treatment, resulting in a lower risk of complication and higher survivability of melanoma patients. Significant factors were stage of the disease, age, histology, sex, and income. Focus should be placed on high-risk populations with severe and aggressive histological subtypes. Programs that emphasize preventive measures such as awareness, education, and early screening could reduce risk.
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•Maximum adsorption capacity (qmax) of Fe(BDC)-MoS2 for Cr(VI) sequestration was 116.36 mg/g.•Significant reduction in the cations (Ni2+, Mn3+, Al3+, Cu2+, Co2+, Pb2+, and Zn2+) and ...anions.•>70 % Removal efficiency in four cycles of easy regeneration and reuse.•Dose-dependent cell toxicity on human cervical epithelial (HeLa) cells in doses of 50–250 μg/mL.
Treatment of paint industry wastewater is challenging due to the presence of interfering ions, tertiary organics and radical species beyond acceptable levels. Further, the synthetic nature of adsorbent poses a risk in post-adsorption waste disposal due to hightened chances of environmental damage or toxicity. Therefore, this reported study focuses on the development of an ecofriendly heterogeneous composite by hydrothermal process using Iron-terephthalic acid (BDC), Metal-organic framework (MOF), and Molybdenum disulphide (MoS2)-together named Fe(BDC)-MoS2. This composite was tested for adsorption of Cr(VI) available in paint industry effluent wastewater (PW). The characterization of the Fe(BDC)-MoS2 using SEM, XRD, XPS, FTIR, revealed resilient formation of the composite. The maximum adsorption capacity (qmax) for Cr(VI) was 116.36 mg/g at 1.0 g/L Fe(BDC)-MoS2 dose at pH 5.13. Fe(BDC)-MoS2 readily adsorbed Cr(VI) from PW with ∼ 99.99 % effecieny. Significant reduction in the co-existing cations (e.g., Ni2+, Mn3+, Al3+, Cu2+, Co2+, Pb2+, and Zn2+) and anions (e.g. Chloride, Sulfate, and Nitrate) was also observed. The reusability study demonstrated a drop in adsorption efficiency by about 25 % after 4 consecutive cycles. The toxicity study on the human cervical epithelial (HeLa) cells at 50 μg/m Fe(BDC)-MoS2 dose showed cell viability of 95, while at 250 μg/Ml, it was 26.5 %. Overall, this study demonstrated Fe(BDC)-MoS2 as an ecofriendly and viable adsorbent for treating industrial wastewater.
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