HIPK2 reduces the resistance of gastric cancer cells to cisplatin via p53 pathway

Purpose: To uncover the functional effect of homologous domain-associated protein kinase 2 (HIPK2) on the viability of cisplatin (DDP)-resistant gastric cancer (GC) cells and elucidate the possible mechanism of action.Methods: The effect of DDP on GC viability and apoptotic rate was evaluated using MTT and flow cytometry (FCM) assays. The potential effect of HIPK2 on DDP sensitivity and cell apoptosis was investigated in the presence of cisplatin while the effect of HIPK2 on p53 activation was determined by immunoblot assay.Results: HIPK2 expression was decreased in DDP-resistant GC cell while upregulation of HIPK2 reduced growth, but promoted apoptosis in DDP-resistant GC cells. Further investigations showed that HIPK2 promoted p53 activation, while suppression of p53 weakened the inhibitory effect of HIPK2 on DDP-resistance in GC cells.Conclusion: The results suggest that HIPK2 is a promising and important therapeutic factor for the regulation of the resistance of GC cells to DDP. Thus, may have a role to play in the management of gastric cancer Keywords: Gastric cancer, Cisplatin, HIPK2, Homologous domain-associated protein kinase 2, p53 pathway, Therapeutic targe

Predicted percentage dissatisfied with vertical temperature gradient

A vertical thermally stratified environment provides opportunities for improved ventilation effectiveness and energy efficiency, but vertical temperature gradient can also cause local thermal discomfort. ASHRAE 55 and ISO 7730 prescribe a 3 °C/m limit between head and feet for seated persons. However, an increasing amount of evidence suggests that this limit is too restrictive. To revisit how vertical temperature gradient affects local thermal comfort, we conducted laboratory tests with four nominal vertical temperature gradients (0.4, 2.9, 5.9, and 8.4 °C/m). Ninety-eight seated college-age students participated in a blind within-subject experiment. Cold-feet discomfort is more frequently rated than warm-head discomfort with increasing temperature gradients. By using logistic regression modeling, we show that the whole-body dissatisfaction increases only slightly (< 10 %) with vertical temperature gradient, even up to 8.4 °C/m. Sex does not significantly affect the results except at 8.4 °C/m. Acceptable vertical temperature gradient changes with thermal sensation votes. The results suggest that the vertical temperature gradient could be increased to 5 °C/m between head and feet when the subject is thermally neutral

Review of fan-use rates in field studies and their effects on thermal comfort, energy conservation, and human productivity

This paper is a literature review of field studies on fan-use rates and their effects on thermal comfort, energy conservation, and human productivity. In the assessed literature, fans are more popular in Asia, and more used in mixed-mode (MM) and naturally ventilated (NV) buildings than in air-conditioned (AC) buildings. On the basis of collected fan-use models, probit regression models of fan-use rates and ambient environments were obtained and indicate that the essential trigger of fan-use is a warm environment rather than building types. This result helps us to understand the control behaviors and comfort requirements of occupants. Also, fans could provide benefits in three aspects: widening neutral temperatures, saving energy, and improving occupants’ productivity. First, using fans in buildings elevates the neutral temperature and the upper limit of neutral zone (0.5 thermal sensation scale) averages by about 3 K in ranges from 25.7℃ to 28.7℃ and 27.5℃ to 30.7℃, respectively. Second, fan-use reduces AC-use rates in MM buildings in summer. The regression models based on the collected AC-use rate models illustrate that, on average, AC-use is expected to be reduced by about 15% in summer when fans are used. Third, providing occupants access to fans could improve occupants’ productivity. Based on the limited data available, a 3-K temperature extension is achieved by fans ensuring productivity not decreasing. This review could shed some light on the extension of the neutral temperature range, predictions of MM buildings’ energy consumptions, and methods to enhance productivity. Additionally, this review suggests some valuable directions for future research on fans

Semantic-Aware Fine-Grained Correspondence

Establishing visual correspondence across images is a challenging and essential task. Recently, an influx of self-supervised methods have been proposed to better learn representations for visual correspondence. However, we find that these methods often fail to leverage semantic information and over-rely on the matching of low-level features. In contrast, human vision is capable of distinguishing between distinct objects as a pretext to tracking. Inspired by this paradigm, we propose to learn semantic-aware fine-grained correspondence. Firstly, we demonstrate that semantic correspondence is implicitly available through a rich set of image-level self-supervised methods. We further design a pixel-level self-supervised learning objective which specifically targets fine-grained correspondence. For downstream tasks, we fuse these two kinds of complementary correspondence representations together, demonstrating that they boost performance synergistically. Our method surpasses previous state-of-the-art self-supervised methods using convolutional networks on a variety of visual correspondence tasks, including video object segmentation, human pose tracking, and human part tracking.Comment: 26 page

Assessment of causal associations between uric acid and 25-hydroxyvitamin D levels

BackgroundPrevious observational studies have revealed the association between serum uric acid and 25-hydroxyvitamin D. However, the causality and the direction of the associations remain unknown. Thus, we performed a two-sample bidirectional Mendelian Randomization (MR) analysis to investigate the causal association between uric acid and 25-hydroxyvitamin D and to determine the direction of the association.MethodBased on the summary-level GWAS data from large genome-wide association studies, several steps were taken in our analysis to select eligible single-nucleotide polymorphisms (SNPs), which were strongly related to exposure as the instrumental variables. We used different analytical methods, such as inverse-variance weighting (IVW) method, weighted median, MR-Egger regression, and weighted mode method, to make our result more robust and reliable. The IVW method was used as the primary analysis. The Cochran’s Q test, MR-Egger intercept test, MR-PRESSO method, and “leave-one-out” sensitivity analysis was performed to evaluate the heterogeneities, horizontal pleiotropy, and robustness of the results. MR analyses were also conducted using genetic risk scores (GRS) as instrumental variables in both directions by using the same summary-level GWAS data.ResultsOur two-sample MR analysis suggested a causal association of genetically predicted uric acid on 25-hydroxyvitamin D [IVW method: β(SE), −0.0352(0.0149); p = 0.0178], which suggested that a per mg/dl increase in uric acid was associated with a decrease of 0.74 nmol/L of 25-hydroxyvitamin D, and the above results remained stable in the sensitivity analysis. By contrast, four MR methods suggested no causal relationship of 25-hydroxyvitamin D on serum uric acid [IVW β(SE), 0.0139 (0.0635); p = 0.826; MR-Egger β(SE), 0.0671 (0.108); p = 0.537; weighted median β(SE), 0.0933 (0.0495); p = 0.0598; weighted mode β(SE), 0.0562 (0.0463); p = 0.228, respectively]. After excluding the SNPs, which were associated with confounding factors and outlier SNPs, the IVW method suggested that there was still no causal association of 25-hydroxyvitamin D on serum uric acid. The GRS approach showed similar results.ConclusionsSerum uric acid may causally affect the 25-hydroxyvitamin D levels, whereas the causal role of 25-hydroxyvitamin D on uric acid was not supported in our MR analysis. Our findings suggest that increased levels of uric acid should prompt investigation for vitamin D deficiency

A Universal Semantic-Geometric Representation for Robotic Manipulation

Robots rely heavily on sensors, especially RGB and depth cameras, to perceive and interact with the world. RGB cameras record 2D images with rich semantic information while missing precise spatial information. On the other side, depth cameras offer critical 3D geometry data but capture limited semantics. Therefore, integrating both modalities is crucial for learning representations for robotic perception and control. However, current research predominantly focuses on only one of these modalities, neglecting the benefits of incorporating both. To this end, we present Semantic-Geometric Representation (SGR), a universal perception module for robotics that leverages the rich semantic information of large-scale pre-trained 2D models and inherits the merits of 3D spatial reasoning. Our experiments demonstrate that SGR empowers the agent to successfully complete a diverse range of simulated and real-world robotic manipulation tasks, outperforming state-of-the-art methods significantly in both single-task and multi-task settings. Furthermore, SGR possesses the unique capability to generalize to novel semantic attributes, setting it apart from the other methods

Pročišćavanje i karakterizacija fibrinolitičkog enzima iz plijesni Rhizopus microsporus var. tuberosus

Extracellular fibrinolytic enzyme from Rhizopus microsporus var. tuberosus was purified and characterised. The microorganism was isolated in a distillery from daqu, a fermentative agent used in the production of Chinese liquor and vinegar at diff erent temperatures. The fibrinolytic enzyme was partially purifi ed by ammonium sulphate precipitation, dialysis, DEAE Sepharose® Fast Flow ion exchange chromatography and Sephadex G-75 gel filtration chromatography. The molecular mass of the fi brinolytic enzyme was estimated to be 24.5 kDa by SDS-PAGE. The purified enzyme showed optimal activity at pH=7.0 and 37 °C by fibrin plate method. It showed stronger resistance to the inhibition by trypsin and was stable at 37 °C retaining 96.1 % residual activity aft er 4 h of incubation. The fibrinolytic activity of the enzyme was enhanced by Na+, Ca2+, Mg2+ and Mn2+. Conversely, Zn2+ and Cu2+ partly inhibited enzymatic activity. Using fibrin plate method, we found that the enzyme not only degrades fibrin directly, but also activates plasminogen into plasmin to degrade fibrin. The results indicate that the pure enzyme has a potential in dissolving blood clot, and the possibility for application in the treatment of thrombosis.U radu je pročišćen i ispitan izvanstanični fibrinolitički enzim iz plijesni Rhizopus microsporus var. tuberosus. Mikroorganizam je izoliran u distileriji iz starter kulture koja se koristi za fermentaciju tradicionalnog kineskog likera i octa pri različitim temperaturama, tzv. daqu. Fibrinolitički je enzim djelomično pročišćen taloženjem pomoću amonijevog sulfata, dijalizom, ionskom kromatografijom na koloni DEAE Sepharose Fast Flow i gel-filtracijskom kromatografijom na koloni Sephadex G-7. Molekularna masa fibrinolitičkog enzima, određena pomoću SDS-PAGE, iznosila je 24,5 kDa. Optimalni uvjeti za aktivnost pročišćenog enzima bili su pH=7,0 i 37 °C. Enzim je bio otporan na inhibiciju tripsinom, stabilan pri 37 °C, te je zadržao 96,1 % aktivnosti nakon 4 sata inkubacije. Fibrinolitička se aktivnost enzima pojačala u prisutnosti iona Na+, Ca2+, Mg2+ i Mn2+, dok su ioni Zn2+ i Cu2+ djelomično inhibirali njegovu aktivnost. Utvrđeno je da enzim izravno razgrađuje fibrin, i aktivira plazminogen, pri čemu nastali plazmin razgrađuje fibrin. Rezultati pokazuju da se pročišćeni enzim može primijeniti u liječenju tromboze, jer ima sposobnost razgradnje krvnih ugrušaka

EGFR inhibitor C225 increases the radiosensitivity of human lung squamous cancer cells

Background: The purpose of the present study is to investigate the direct biological effects of the epidermal growth factor receptor (EGFR) inhibitor C225 on the radiosensitivity of human lung squamous cancer cell-H520. H520 cells were treated with different dosage of (60)Co gamma ray irradiation (1.953 Gy/min) in the presence or absence of C225. The cellular proliferation, colony forming capacity, apoptosis, the cell cycle distribution as well as caspase-3 were analyzed in vitro. Results: We found that C225 treatment significantly increased radiosensitivity of H-520 cells to irradiation, and led to cell cycle arrest in G(1) phase, whereas (60)Co gamma ray irradiation mainly caused G(2) phase arrest. H-520 cells thus displayed both the G(1) and G(2) phase arrest upon treatment with C225 in combination with (60)Co gamma ray irradiation. Moreover, C225 treatment significantly increased the apoptosis percentage of H-520 cells (13.91% +/- 1.88%) compared with the control group (5.75% +/- 0.64%, P < 0.05). Conclusion: In this regard, C225 treatment may make H-520 cells more sensitive to irradiation through the enhancement of caspase-3 mediated tumor cell apoptosis and cell cycle arrest.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000284001800001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701OncologySCI(E)PubMed2ARTICLE391

Central Angiotensin II Stimulation Promotes β Amyloid Production in Sprague Dawley Rats

BACKGROUND: Stress and various stress hormones, including catecholamines and glucocorticoids, have recently been implicated in the pathogenesis of Alzheimer's disease (AD), which represents the greatest unresolved medical challenge in neurology. Angiotensin receptor blockers have shown benefits in AD and prone-to-AD animals. However, the mechanisms responsible for their efficacy remain unknown, and no studies have directly addressed the role of central angiotensin II (Ang II), a fundamental stress hormone, in the pathogenesis of AD. The present study focused on the role of central Ang II in amyloidogenesis, the critical process in AD neuropathology, and aimed to provide direct evidence for the role of this stress hormone in the pathogenesis of AD. METHODOLOGY/PRINCIPAL FINDINGS: Increased central Ang II levels during stress response were modeled by intracerebroventricular (ICV) administration of graded doses of Ang II (6 ng/hr low dose, 60 ng/hr medium dose, and 600 ng/hr high dose, all delivered at a rate of 0.25 µl/hr) to male Sprague Dawley rats (280-310 g) via osmotic pumps. After 1 week of continuous Ang II infusion, the stimulation of Ang II type 1 receptors was accompanied by the modulation of amyloid precursor protein, α-, β-and γ-secretase, and increased β amyloid production. These effects could be completely abolished by concomitant ICV infusion of losartan, indicating that central Ang II played a causative role in these alterations. CONCLUSIONS/SIGNIFICANCE: Central Ang II is essential to the stress response, and the results of this study suggest that increased central Ang II levels play an important role in amyloidogenesis during stress, and that central Ang II-directed stress prevention and treatment might represent a novel anti-AD strategy