Curcumin Sensitises Cancerous Kidney Cells to TRAIL Induced Apoptosis via Let-7C Mediated Deregulation of Cell Cycle Proteins and Cellular Metabolism

Targeted therapies are the most attractive options in the treatment of different tumours, including kidney cancers. Such therapies have entered a golden era due to advancements in research, breakthroughs in scientific knowledge, and a better understanding of cancer therapy mechanisms, which significantly improve the survival rates and life expectancy of patients. The use of tumour necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) as an anticancer therapy has attracted the attention of the scientific community and created great excitement due to its selectivity in targeting cancerous cells with no toxic impacts on normal tissues. However, clinical studies disappointingly showed the emergence of resistance against TRAIL. This study aimed to employ curcumin to sensitise TRAIL-resistant kidney cancerous ACHN cells, as well as to gain insight into the molecular mechanisms of TRAIL sensitization. Curcumin deregulated the expression of apoptosis-regulating micro Ribonucleic Acid (miRNAs), most notably, let-7C. Transfecting ACHN cells with a let-7C antagomir significantly increased the expression of several cell cycle protein, namely beta (β)-catenin, cyclin dependent kinase (CDK)1/2/4/6 and cyclin B/D. Further, it overexpressed the expression of the two key glycolysis regulating proteins including hypoxia-inducible factor 1-alpha (HIF-1α) and pyruvate dehydrogenase kinase 1 (PDK1). Curcumin also suppressed the expression of the overexpressed proteins when added to the antagomir transfected cells. Overall, curcumin targeted ACHN cell cycle and cellular metabolism by promoting the differential expression of let-7C. To the best of our knowledge, this is the first study to mechanistically report the cancer chemosensitisation potential of curcumin in kidney cancer cells via induction of let-7C.     

设备供应商迎来工业4.0——自动化、数字化、机器学习已成为卫生用品行业新标准

工业4.0——也被称为第四次工业革命、智能制造、或IloT(工业物联网)——已经在卫生用品行业中扎根.机械设备制造商已经开发出了应用于制造业中的新交互平台,包括自动化、数字化、M2M(机器对机器)技术、机器学习、实时数据等等. 行业应用 虽然工业4.0仍处于早期阶段,也并非没有挑战,但全球各地的组织已经开始看到工业4....     

Exposures to transit and other sources of noise among New York City residents

To evaluate the contributions of common noise sources to total annual noise exposures among urban residents and workers, we estimated exposures associated with five common sources (use of mass transit, occupational and nonoccupational activities, MP3 player and stereo use, and time at home and doing other miscellaneous activities) among a sample of over 4500 individuals in New York City (NYC). We then evaluated the contributions of each source to total noise exposure and also compared our estimated exposures to the recommended 70 dBA annual exposure limit. We found that one in ten transit users had noise exposures in excess of the recommended exposure limit from their transit use alone. When we estimated total annual exposures, 90% of NYC transit users and 87% of nonusers exceeded the recommended limit. MP3 player and stereo use, which represented a small fraction of the total annual hours for each subject on average, was the primary source of exposure among the majority of urban dwellers we evaluated. Our results suggest that the vast majority of urban mass transit riders may be at risk of permanent, irreversible noise-induced hearing loss and that, for many individuals, this risk is driven primarily by exposures other than occupational noise.     

Productive Interrelationships between Collaborative Groups Ease the Challenges of Dynamic and Multi-Teaming

Work organization and team membership is highly complex for modern workers. Teams are often dynamic as personnel change during a project. Dynamic team members have to be actively recruited and personnel changes make it harder for participants to retain group focus. Workers are often members of multiple groups. Though prior work has identified the prevalence of multi-teaming and dynamic teams, it has been unable to explain how workers cope with the challenges the new style of work should cause. This paper systematically characterizes the modern organizational landscape from an individual perspective, by studying how people typically organize work across their multiple collaborative groups. A unique contribution of our work is to examine the interrelationships between the collaborative groups individuals typically participate in. We introduce the notion of a collaboration profile to characterize these interrelations. We expected workers to be overburdened by contributing to multiple teams often with shifting personnel. However, we found that multi-teaming involves productive interrelationships between collaborative groups that ease some of the documented challenges of dynamic teams, such as goal setting, recruiting, and group maintenance. We define a typology that describes the various types of collaborative groups workers participate in, and provide examples of productive interrelations between collaborations. In characterizing interrelations between collaborations, we provide detailed examples of how people exploit resources across their different collaborations to address the problems of working in multiple dynamic teams.     

Thermal,mechanical, and barrier properties of polyethylene terephthalate‐platelet nanocomposites prepared by in situ polymerization

This study used in situ polymerization to prepare polyethylene terephthalate (PET) nanocomposites incorporating Ethoquad‐modified montmorillonite (eMMT), unmodified hectorite (HCT), or phenyl hectorite (phHCT) particles to study the impact of platelet surface chemistry and loading on thermal, mechanical, and gas barrier properties. eMMT platelets reduced the PET crystallization rate without altering the ultimate degree of crystallinity. In contrast, HCT and phHCT platelets accelerated the polymer's crystallization rate and increased its crystallinity. DMA results for thermally‐quenched samples showed that as T increased past glass transition temperature (T_g), HCT and phHCT nanocomposites (and control PET) manifested precipitous drops in G′ followed by increasing G′ due to cold crystallization; in contrast, eMMT nanocomposites had much higher G′ values around T_g. This provides direct evidence of eMMT reinforcement in thermally‐quenched eMMT nanocomposites. These results suggest that eMMT has a strong, favorable interaction with PET, possibly through Ethoquad‐PET entanglement. HCT and phHCT have a fundamentally different interaction with PET that increases crystallization rate and T_g by 11 to 17°C. Water barrier improvement in eMMT nanocomposites agrees with previously published oxygen barrier results and can be rationalized in terms of a tortuous path gas barrier model. POLYM. ENG. SCI., 52:1888–1902, 2012. © 2012 Society of Plastics Engineers     

Reduction of Furan Formation by High-Pressure High-Temperature Treatment of Individual Vegetable Purées

The present study addressed the need for furan mitigation measures at the level of food production, where the effects of extrinsic (process-related) and intrinsic (product-related) properties on furan formation in vegetable-based systems were investigated. For the first time in the literature, the effect of high-pressure high-temperature (HPHT) processing on the formation of furan was demonstrated. HPHT processing was proven to be an interesting alternative for furan reduction in vegetable-based systems, when aiming for sterilization intensities. Following HPHT treatment, the furan concentrations of a wide range of individual vegetable purées dropped to levels close to the analytical limits (1–2 ng/g purée). A higher processing cost might limit the use of HPHT processing to high-value added products, which means that for many other conduction-heated food products, conventional heating would remain the standard technology. As a first step towards control of furan formation in the latter products, a mixed model regression was used to identify the major precursors in vegetable-based systems. Significant correlations were observed for vitamin C and sugars, which were attributed to the efficiency of the conversion and high concentrations, respectively. Next to furan, the HPHT- and thermally treated purées were analyzed for 2- and 3-methylfuran, which are likely to undergo the same metabolic fate as furan. For most of the vegetables tested, the total amount of methylfuran found in the thermally treated purées could not be ignored. Similarly to furan, there was a clear reduction in the concentrations found in the HPHT-treated purées.     

Binding Mode and Structure–Activity Relationships around Direct Inhibitors of the Nrf2–Keap1 Complex

An X‐ray crystal structure of Kelch‐like ECH‐associated protein (Keap1) co‐crystallised with (1S,2R)‐2‐[(1S)‐1‐[(1,3‐dioxo‐2,3‐dihydro‐1H‐isoindol‐2‐yl)methyl]‐1,2,3,4‐tetrahydroisoquinolin‐2‐carbonyl]cyclohexane‐1‐carboxylic acid (compound (S,R,S)‐ 1 a ) was obtained. This X‐ray crystal structure provides breakthrough experimental evidence for the true binding mode of the hit compound (S,R,S)‐ 1 a , as the ligand orientation was found to differ from that of the initial docking model, which was available at the start of the project. Crystallographic elucidation of this binding mode helped to focus and drive the drug design process more effectively and efficiently.     

A stress-coping profile of opioid dependent individuals entering naltrexone treatment: A comparison with healthy controls.

Background: Stress is known to increase addiction vulnerability and risk of relapse to substance use. Purpose & Method: We compared opioid dependent individuals entering naltrexone treatment (n = 57) with healthy controls (n = 75) on measures of stress, coping, and social support and examined the relative contribution of group membership, coping, and social support to stress within the sample. Analyses of variance (ANOVA) and covariance (ANCOVA), and stepwise multiple regression were conducted. Results: Compared with controls, opioid dependent subjects reported greater stress, less use of adaptive coping, but comparable use of maladaptive/avoidant coping. No group differences were found with respect to social support. Perceived stress was predicted by group membership, low social support, and greater use of maladaptive/avoidant coping, and the prediction by social support and maladaptive/avoidant coping did not differ by group. Conclusion: Opioid dependent individuals entering naltrexone treatment experience higher levels of stress and report less use of adaptive coping strategies when compared with controls. Group membership, maladaptive/avoidant coping, and social support independently contribute to perceived stress. Findings suggest that novel treatment approaches that decrease maladaptive/avoidant coping and improve social support are important aspects of decreasing stress during early recovery from opioid addiction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)