Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is latent but constitutively activated in many types of cancers. It is well known that STAT3 plays a key role ...in inflammation-associated tumorigenesis. Curcumin is an anti-inflammatory natural compound isolated from the turmeric (Curcuma longa L., Zingiberaceae) that has been extensively used in a traditional medicine over the centuries. In the present study, we have found that curcumin inhibits STAT3 signaling that is persistently overactivated in H-Ras transformed breast epithelial cells (H-Ras MCF10A). Specific cysteine residues present in STAT3 appear to be critical for the activity as well as conformation of this transcription factor. We identified the cysteine residue 259 of STAT3 as a putative site for curcumin binding. Site-directed mutation of this cysteine residue abolished curcumin-induced inactivation of STAT3 and apoptosis in H-Ras MCF10A cells. The α,β-unsaturated carbonyl moiety of curcumin appears to be essential in its binding to STAT3 in H-Ras MCF10A cells. Tetrahydrocurcumin that lacks such electrophilic moiety failed to interact with STAT3 and to induce apoptosis in the same cell line. Taken together, our findings suggest that curcumin can abrogate aberrant activation of STAT3 through direct interaction, thereby inhibiting STAT3-mediated mammary carcinogenesis.
Forward osmosis (FO) has been increasingly studied in the past decade for its potential as an emerging low-energy water and wastewater treatment process. However, the term “low-energy” may only be ...suitable for those applications in where no further treatment of the draw solution (DS) is required either in the form of pretreatment or post-treatment to the FO process (e.g. where the diluted DS is the targeted final product which can be used directly or simply discarded). In most applications, FO has to be coupled with another separation process in a so-called hybrid FO system to either separate the DS from the final product water or to be used as an advanced pre-treatment process to conventional desalination technologies. The additional process increases the capital cost as well as the energy demand of the overall system which is one of the several challenges that hybrid FO systems need to overcome to compete with other separation technologies. Yet, there are some applications where hybrid FO systems can outperform conventional processes and this study aims to provide a comprehensive review on the current state of hybrid FO systems. The recent development and performance of hybrid FO systems in different applications have been reported. This review also highlights the future research directions for the current hybrid FO systems to achieve successful implementation.
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•In most applications, FO is coupled with another process to form a hybrid system.•The recent development and performance of hybrid FO systems have been reviewed.•Hybrid FO systems can outperform conventional processes in some applications.•Future research directions to achieve full-scale implementation have been discussed.
This article proposes a wireless power transfer (WPT) system for variant receiver (Rx) configuration, power distribution ratio, load, and distance with multiple relays, each of which is connected to ...a resistive load. Each Rx relay transfers power to an adjacent Rx and acts as a relay while its local load consumes power. We develop a methodology for the design of WPT resonators that achieve optimum efficiency for multiple receivers with power distribution ratios, loads, and distances. The WPT configuration is extended to a general m×n, two-dimensional grid for a large area coverage. A mathematical model of the proposed WPT system is provided, and a multiple-Rx wireless power network using a power inverter serves as a proof-of-concept. Following the design guidelines provided in this article, experimental examples with variable parameters while delivering a total power of 100 W are discussed. To illustrate the practical applicability of this approach, a demonstration on a consumer display and speaker device is performed.
The diamond–graphite hybrid thin film with low‐dimensional nanostructure (e.g., nitrogen‐included ultrananocrystalline diamond (N‐UNCD) or the alike), has been employed in many impactful breakthrough ...applications. However, the detailed picture behind the bottom–up evolution of such intriguing carbon nanostructure is far from clarified yet. Here, the authors clarify it, through the concerted efforts of microscopic, physical, and electrochemical analyses for a series of samples synthesized by hot‐filament chemical vapor deposition using methane–hydrogen precursor gas, based on the hydrogen‐dependent surface reconstruction of nanodiamond and on the substrate‐temperature‐dependent variation of the growth species (atomic hydrogen and methyl radical) concentration near substrate. The clarified picture provides insights for a drastic enhancement in the electrochemical activities of the hybrid thin film, concerning the detection of important biomolecule, that is, ascorbic acid, uric acid, and dopamine: their limits of detections are 490, 35, and 25 nm, respectively, which are among the best of the all‐carbon thin film electrodes in the literature. This work also enables a simple and effective way of strongly enhancing AA detection.
The authors clarify the nucleation/growth mechanism of diamond–graphite hybrid thin film with 2D nanostructure (the only successful diamond probe material for neural recording/stimulation), based on nanodiamond surface reconstruction controlled by growth species variation in growth environment. It provides insights for the drastic enhancement of the structure‐optimized thin film performance in simultaneous electrochemical detection of dopamine, ascorbic acid, and uric acid.
Upon mating, fruit fly females become refractory to further mating for several days. An ejaculate protein called sex peptide (SP) acts on uterine neurons to trigger this behavioural change, but it is ...still unclear how the SP signal modifies the mating decision. Here we describe two groups of female-specific local interneurons that are important for this process-the ventral abdominal lateral (vAL) and ventral abdominal medial (vAM) interneurons. Both vAL and vAM express myoinhibitory peptide (Mip)-GAL4. vAL is positive for Mip neuropeptides and the sex-determining transcriptional factor doublesex. Silencing the Mip neurons in females induces active rejection of male courtship attempts, whereas activation of the Mip neurons makes even mated females receptive to re-mating. vAL and vAM are located in the abdominal ganglion (AG) where they relay the SP signal to other AG neurons that project to the brain. Mip neuropeptides appear to promote mating receptivity both in virgins and mated females, although it is dispensable for normal mating in virgin females.
Many studies have reported the effect of hypertension on microcirculation of the retina. Advance of optical coherence tomography angiography (OCTA) allows us more detailed observations of ...microcirculation of the retina. Therefore, we compared OCTA parameters between chronic hypertension (disease duration of at least 10 yrs; Group A, 45 eyes), relieved hypertensive retinopathy (grade IV HTNR < 1 yr prior; Group B, 40 eyes), and normal controls Group C (50 eyes) ≥ 50 yrs old and Group D (50 eyes) < 50 yrs old. A 3 × 3 mm macular scan was performed in each group by OCTA. In vessel density of 3 mm full, group A and B were significantly decreased compared to normal control group (Group A vs. C; 19.4 mm
vs. 20.1 mm
, Group B vs. D; 19.8 mm
vs. 21.8 mm
, all p < 0.05). In foveal avascular zone, group A and B were significantly increased compared to normal control group (Group A vs. C; 0.35 mm
vs. 0.30 mm
, Group B vs. D; 0.36 mm
vs. 0.29 mm
, all p < 0.05). OCTA is useful for examining retinal microcirculatory changes in hypertension and we confirmed that hypertension affects the OCTA parameters. Considering the effect of hypertension on the change of microvasculature, care is required in the interpretation of OCTA parameters in various ophthalmic condition.
In this letter, a compact branch-line-based quadrature hybrid coupler using a line miniaturization technique for a 28-GHz application is presented. Coplanar waveguide-based artificial transmission ...lines are used in the miniaturization, and T-equivalent circuit models are exploited to elaborate on the optimization method. A multistage T-model is utilized to eliminate the need for lumped elements, improve bandwidth performance, and simplify the fabrication process. To validate the proposed approach, the designed quadrature hybrid coupler was fabricated on a glass substrate. The measured insertion loss and phase difference at 28 GHz were 3.86 dB, 3.94 dB, and 90.4°, respectively. The output amplitude imbalance was within a 1-dB range from 25.3 to 31.0 GHz, and the total device area, excluding the measurement pad, was <inline-formula> <tex-math notation="LaTeX">1.15\times0.98 </tex-math></inline-formula> mm 2 .
The endoplasmic reticulum (ER) is a dynamic organelle that synthesizes and folds proteins. An imbalance between the ER protein synthesis load and its folding capacity triggers the unfolded protein ...response, thereby restoring normal ER functions via size adjustment. Inspired by such inherent genetic programming events, we engineered Saccharomyces cerevisiae to expand the ER by overexpressing a key ER size regulatory factor, INO2. ER space expansion enhanced ER protein synthesis and folding capacity, and relieved metabolic constraints imposed by the limited enzyme abundance. Harnessing the yeast ER for metabolic engineering, we ultimately increased the production of squalene and cytochrome P450-mediated protopanaxadiol by 71-fold and 8-fold, compared to their respective control strains without overexpression of INO2. Furthermore, genome-wide transcriptome analysis of the ER-expanded strain revealed that the significant improvement in terpene production was associated with global rewiring of the metabolic network. Therefore, the yeast ER can be engineered as a specialized compartment for enhancing terpene production, representing new possibilities for the high-level production of other value-added chemicals.
•This study aims to harness yeast endoplasmic reticulum (ER) for functional assembly of challenging metabolic pathways.•ER expansion can lead to increased abundance of ER-associated enzymes and consequential improvement in metabolic capacity.•ER expansion increased production of squalene and cytochrome P450-mediated protopanaxadiol by 71- and 8-fold, respectively.•The squalene titer of 634 mg/L was achieved by shake flask fermentation, the highest titer reported to date in S. cerevisiae.•RNA-seq analysis provides novel frameworks for designing genetic network to construct a platform cell for terpene synthesis.
An accurate tool enabling early diagnosis of hepatocellular carcinoma (HCC) is clinically important, given that early detection of HCC markedly improves survival. We aimed to investigate the ...molecular markers underlying early progression of HCC that can be detected in precancerous lesions. We designed a gene selection strategy to identify potential driver genes by integrative analysis of transcriptome and clinicopathological data of human multistage HCC tissues, including precancerous lesions, low‐ and high‐grade dysplastic nodules. The gene selection process was guided by detecting the selected molecules in both HCC and precancerous lesion. Using various computational approaches, we selected 10 gene elements as a candidate and, through immunohistochemical staining, showed that barrier to autointegration factor 1 (BANF1), procollagen‐lysine, 2‐oxoglutarate 5‐dioxygenase 3 (PLOD3), and splicing factor 3b subunit 4 (SF3B4) are HCC decision markers with superior capability to diagnose early‐stage HCC in a large cohort of HCC patients, as compared to the currently popular trio of HCC diagnostic markers: glypican 3, glutamine synthetase, and heat‐shock protein 70. Targeted inactivation of BANF1, PLOD3, and SF3B4 inhibits in vitro and in vivo liver tumorigenesis by selectively modulating epithelial‐mesenchymal transition and cell‐cycle proteins. Treatment of nanoparticles containing small‐interfering RNAs of the three genes suppressed liver tumor incidence as well as tumor growth rates in a spontaneous mouse HCC model. We also demonstrated that SF3B4 overexpression triggers SF3b complex to splice tumor suppressor KLF4 transcript to nonfunctional skipped exon transcripts. This contributes to malignant transformation and growth of hepatocyte through transcriptional inactivation of p27Kip1 and simultaneously activation of Slug genes. Conclusion: The findings suggest molecular markers of BANF1, PLOD3, and SF3B4 indicating early‐stage HCC in precancerous lesion, and also suggest drivers for understanding the development of hepatocarcinogenesis. (Hepatology 2018;67:1360‐1377).
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