Increased Endogenous Nitric Oxide Release by Iron Chelation and Purinergic Activation in the Rat Carotid Body

We examined the hypothesis that hypoxic chemotransduction with stabilization of HIF-1 and activation of purinoceptors stimulate the endogenous NO production in the rat carotid body. The effects of blockade of purinoceptors with suramin, or blockade of HIF-1α hydroxylation by suppressing prolyl hydroxylase (PAH) activity on the endogenous NO release measured electrochemically by microsensor inserted into the isolated carotid body superfused with bicarbonate-buffer were examined. Suramin did not change the resting NO level under normoxic conditions but it significantly decreased the hypoxia-induced NO elevation in a dose-dependent manner. Suramin (100μM) blocked the NO response to acute hypoxia by 53%. Intracellular iron chelator, ciclopirox olamine (CPX) significantly increased the resting NO release close to the hypoxic level, which was reversed by FeSO4 or blocked by L-NMMA. Also, PAH inhibition with dimethy-loxalylglycine (DMOG) moderately increased the resting NO release. In the presence of CPX and DMOG the resting NO release was increased to the hypoxic level. Collectively, results suggest that iron chelation and purinoceptor stimulation play a role in the hypoxic chemotransduction for an increase in the endogenous NO production in the rat carotid body

Practical Cross-system Shilling Attacks with Limited Access to Data

In shilling attacks, an adversarial party injects a few fake user profiles into a Recommender System (RS) so that the target item can be promoted or demoted. Although much effort has been devoted to developing shilling attack methods, we find that existing approaches are still far from practical. In this paper, we analyze the properties a practical shilling attack method should have and propose a new concept of Cross-system Attack. With the idea of Cross-system Attack, we design a Practical Cross-system Shilling Attack (PC-Attack) framework that requires little information about the victim RS model and the target RS data for conducting attacks. PC-Attack is trained to capture graph topology knowledge from public RS data in a self-supervised manner. Then, it is fine-tuned on a small portion of target data that is easy to access to construct fake profiles. Extensive experiments have demonstrated the superiority of PC-Attack over state-of-the-art baselines. Our implementation of PC-Attack is available at https://github.com/KDEGroup/PC-Attack.Comment: Accepted by AAAI 202

Synthesis of dental resins using diatomite and nano-sized SiO2 and TiO2

AbstractThe mechanical properties of dental composites were improved by porous diatomite and nano-sized silica (OX-50) used as co-fillers. The resin composites, filled with silanized OX-50 and silanized diatomite (40:60wt/wt), presented the best flexural strength (133.1MPa), elastic modulus (9.5GPa) and Vickers microhardness (104.0HV). Besides these, TiO2 nanoparticles were introduced to tune the dental resin composites colours which were valued by the CIE-Lab system. The colour parameters (L⁎, a⁎, b⁎) showed that the colour changes of resin composites could be perceived obviously, when 300–400nm TiO2 particles were introduced as fillers. The resin composite, filled with 0.5wt% TiO2, exhibited both clear discolouration (ΔE⁎=3.22) and high mechanical strength. Using scanning electron microscope (SEM) equipped with an energy dispersive X-ray (EDX), the titanium elemental mapping results indicated that the TiO2 particles were distributed evenly in the prepared dental composites

Notch1 promotes resistance to cisplatin by up-regulating Ecto-5'-nucleotidase (CD73) in triple-negative breast cancer cells

Triple-negative breast cancer (TNBC) is an aggressive molecular subtype that due to lack of druggable targets is treated with chemotherapy as standard of care. However, TNBC is prone to chemoresistance and associates with poor survival. The aim of this study was to explore the molecular mechanisms of chemoresistance in TNBC. Firstly, we found that the mRNA expression of Notch1 and CD73 in cisplatin-treated patient material associated with poor clinical outcome. Further, both were upregulated at the protein level in cisplatin-resistant TNBC cell lines. Overexpression of Notch1 intracellular domain (termed N1ICD) increased expression of CD73, whereas knockdown of Notch1 decreased CD73 expression. Using chromatin immunoprecipitation and Dual-Luciferase assay it was identified that N1ICD directly bound the CD73 promoter and activated transcription. Taken together, these findings suggest CD73 as a direct downstream target of Notch1, providing an additional layer to the mechanisms underlying Notch1-mediated cisplatin resistance in TNBC.</p

Electrophysiology as a prognostic indicator of visual recovery in diabetic patients undergoing cataract surgery

Purpose: Visual outcomes after cataract surgery in diabetic patients with retinal or visual pathway disease are difficult to predict as the fundus may be obscured, and assessment of visual potential is challenging. This study assessed the value of visual electrophysiology as a prognostic indicator of visual recovery in diabetic patients with cataract, prior to cataract surgery. Methods: Forty-one diabetic patients (aged 52–80; 74 eyes) and 13 age-matched non-diabetic control patients (21 eyes) were examined prior to cataract surgery. Pre-surgical examinations included best-corrected visual acuity (BCVA), slit-lamp bio-microscopy, ISCEV-standard full-field electroretinography (ffERG), and flash visual evoked potential (flash VEP) testing. Electrophysiological assessments included quantification of the DA and LA ERG, oscillatory potentials (OPs; OP1, OP2, OP3, OP4) and flash VEP P1, P2, and P3 components. Post-operative BCVA was measured in all cases and the diabetic patients grouped according to the severity of visual acuity loss: mild (logMAR ≤ 0.1), moderate (0.1 < logMAR < 0.5), or severe (logMAR ≥ 0.5). A fourth group included those without diabetes. The pre-surgical electrophysiological data was compared between the four groups by analysis of variance. Results: The severity of post-surgical visual acuity loss in the diabetic patients was classified as mild (N=22 eyes), moderate (N=31 eyes), or severe (N=21 eyes). In the group without diabetes, post-surgical visual impairment was classified as mild (N=21 eyes). The pre-operative DA 10.0 ERG a-wave amplitudes, DA 3.0 ERG OP2 amplitudes, and the LA 3.0 a- and b-wave amplitudes showed best significant differences among the four groups. The flash VEP did not show significant difference between groups. Conclusion: Electrophysiological assessment of diabetic patients with cataract can provide a useful measure of retinal function. Full-field ERG components, including the DA 10.0 ERG a-wave, DA 3.0 ERG OP2 component, and the LA 3.0 a- and b-wave amplitudes, are of prognostic value in predicting post-surgical visual acuity, and may inform the surgical management of cataract patients with diabetes. [Figure not available: see fulltext.]

High-resolution characterization of the coagulation and drying processes of whole blood based on optical coherence tomography

Introduction: Escaping whole blood exhibits biochemical and physical coupled mechanisms such as coagulation and drying. However, there is no method for simultaneously monitoring the coagulation and drying procedure.Methods: In this study, a new method based on optical coherence tomography (OCT) combined with speckle variance and thickness is presented for simultaneously capturing spatially high-resolved characteristics of coagulation and drying of whole blood during the procedure. Deep learning based on a convolutional neural network (CNN) is employed for collecting OCT images with a resolution of micron order and quantitatively obtaining pixel-wise information of whole blood.Results and discussion: Then, the pixel-wise thickness map provides high-resolved temporal–spatial dynamics of whole blood during the drying procedure, and the corresponding speckle variance can uncover information of whole blood coagulation. The results demonstrate that coagulation and drying of whole blood have spatially inhomogeneous features. This method could provide the potential for revealing the coupling mechanism between coagulation and drying