O-Linked β-N-acetylglucosamine (O-GlcNAc) modification:emerging pathogenesis and a therapeutic target of diabetic nephropathy

Aims: O-Linked β-N-acetylglucosamine (O-GlcNAc) modification, a unique post-translational modification of proteins, is elevated in diabetic nephropathy. This review aims to summarize the current knowledge on the mechanisms by which O-GlcNAcylation of proteins contributes to the pathogenesis and progression of diabetic nephropathy, as well as the therapeutic potential of targeting O-GlcNAc modification for its treatment.Methods: Current evidence in the literature was reviewed and synthesized in a narrative review.Results: Hyperglycemia increases glucose flux into the hexosamine biosynthesis pathway, which activates glucosamino-fructose aminotransferase expression and activity, leading to the production of O-GlcNAcylation substrate UDP-GlcNAc and an increase in protein O-GlcNAcylation in kidney cells. Protein O-GlcNAcylation regulates the function of kidney cells including mesangial cells, podocytes, and proximal tubular cells, and promotes renal interstitial fibrosis, resulting in kidney damage. Current treatments for diabetic nephropathy, such as sodium-glucose cotransporter 2 (SGLT-2) inhibitors and renin-angiotensin-aldosterone system (RAAS) inhibitors, delay disease progression and suppress protein O-GlcNAcylation. Conclusions: Increased protein O-GlcNAcylation mediates renal cell damage and promotes renal interstitial fibrosis, leading to diabetic nephropathy. Although the full significance of inhibition of O-GlcNAcylation is not yet understood, it may represent a novel target for treating diabetic nephropathy. <br/

Model Inversion Attack via Dynamic Memory Learning

Model Inversion (MI) attacks aim to recover the private training data from the target model, which has raised security concerns about the deployment of DNNs in practice. Recent advances in generative adversarial models have rendered them particularly effective in MI attacks, primarily due to their ability to generate high-fidelity and perceptually realistic images that closely resemble the target data. In this work, we propose a novel Dynamic Memory Model Inversion Attack (DMMIA) to leverage historically learned knowledge, which interacts with samples (during the training) to induce diverse generations. DMMIA constructs two types of prototypes to inject the information about historically learned knowledge: Intra-class Multicentric Representation (IMR) representing target-related concepts by multiple learnable prototypes, and Inter-class Discriminative Representation (IDR) characterizing the memorized samples as learned prototypes to capture more privacy-related information. As a result, our DMMIA has a more informative representation, which brings more diverse and discriminative generated results. Experiments on multiple benchmarks show that DMMIA performs better than state-of-the-art MI attack methods

Association of serum creatinine to cystatin C to waist circumference ratios and hypertension: evidence from China health and retirement longitudinal study

BackgroundThe objective of this study was to explore the association between the ratio of serum creatinine to cystatin C to waist circumference (CCR/WC) and hypertension.MethodsThe study utilized data extracted from the China Health and Retirement Longitudinal Study. In the cross-sectional analysis, logistic regression analyses were employed to examine the association between the CCR/WC ratio and hypertension. By utilizing restricted cubic splines, potential non-linear associations between the CCR/WC ratio and hypertension were explored. In the longitudinal analysis, the association between CCR/WC quartiles (Q1–Q4) and the risk of new-onset hypertension was evaluated by Cox proportional-hazards models.ResultsIn total, 7,253 participants were enrolled. The study unveiled an inverse association with hypertension, demonstrating an odds ratio (OR) of 0.29 (95% confidence interval [CI]: 0.23–0.37, P &lt; 0.001). Among males, an OR of 0.38 (95% CI: 0.25–0.58, P &lt; 0.001) was observed, while among females, an OR of 0.41 (95% CI: 0.28–0.60, P &lt; 0.001) was noted. There was an absence of a nonlinear association between the CCR/WC ratio and hypertension. Cox regression analysis unveiled a reduced risk of hypertension in Q3 (Hazard ratios [HR]: 0.69, 95% CI: 0.58–0.82, P &lt; 0.001) and Q4: (HR: 0.70, 95% CI: 0.59–0.83, P &lt; 0.001) in compared to the Q1 of the CCR/WC ratio, and sex-specific analysis yielded consistent results.ConclusionThis study emphasizes the potential association between an elevated CCR/WC ratio and a reduced risk of hypertension

TransAudio: Towards the Transferable Adversarial Audio Attack via Learning Contextualized Perturbations

In a transfer-based attack against Automatic Speech Recognition (ASR) systems, attacks are unable to access the architecture and parameters of the target model. Existing attack methods are mostly investigated in voice assistant scenarios with restricted voice commands, prohibiting their applicability to more general ASR related applications. To tackle this challenge, we propose a novel contextualized attack with deletion, insertion, and substitution adversarial behaviors, namely TransAudio, which achieves arbitrary word-level attacks based on the proposed two-stage framework. To strengthen the attack transferability, we further introduce an audio score-matching optimization strategy to regularize the training process, which mitigates adversarial example over-fitting to the surrogate model. Extensive experiments and analysis demonstrate the effectiveness of TransAudio against open-source ASR models and commercial APIs

Increased Numbers of NK Cells, NKT-Like Cells, and NK Inhibitory Receptors in Peripheral Blood of Patients with Chronic Obstructive Pulmonary Disease

T cells and B cells participate in the pathogenesis of COPD. Currently, NK cells and NKT cells have gained increasing attention. In the present study, 19 COPD patients and 12 healthy nonsmokers (HNS) were recruited, and their pulmonary function was assessed. The frequencies of CD3+ T, CD4+ T, CD8+ T, B, NK, and NKT-like cells were determined using flow cytometry. The frequencies of spontaneous and inducible IFN-γ+ or CD107a+ NK and NKT-like cells as well as activating or inhibitory receptors were also detected. The potential association of lymphocyte subsets with disease severity was further analyzed. Significantly decreased numbers of CD3+ and CD4+ T cells, and the CD4+/CD8+ ratio, but increased numbers of CD3−CD56+ NK and CD3+CD56+ NKT-like cells were observed in COPD patients compared to HNS. The frequencies of inducible IFN-γ-secreting NK and NKT-like cells were less in COPD patients. The frequencies of CD158a and CD158b on NK cells and CD158b on NKT-like cells were greater. The frequency of CD158b+ NK cells was negatively correlated with FEV1% prediction and FEV1/FVC. Our data indicate that COPD patients have immune dysfunction, and higher frequencies of inhibitory NK cells and NKT-like cells may participate in the pathogenesis of COPD

Enhance the Visual Representation via Discrete Adversarial Training

Adversarial Training (AT), which is commonly accepted as one of the most effective approaches defending against adversarial examples, can largely harm the standard performance, thus has limited usefulness on industrial-scale production and applications. Surprisingly, this phenomenon is totally opposite in Natural Language Processing (NLP) task, where AT can even benefit for generalization. We notice the merit of AT in NLP tasks could derive from the discrete and symbolic input space. For borrowing the advantage from NLP-style AT, we propose Discrete Adversarial Training (DAT). DAT leverages VQGAN to reform the image data to discrete text-like inputs, i.e. visual words. Then it minimizes the maximal risk on such discrete images with symbolic adversarial perturbations. We further give an explanation from the perspective of distribution to demonstrate the effectiveness of DAT. As a plug-and-play technique for enhancing the visual representation, DAT achieves significant improvement on multiple tasks including image classification, object detection and self-supervised learning. Especially, the model pre-trained with Masked Auto-Encoding (MAE) and fine-tuned by our DAT without extra data can get 31.40 mCE on ImageNet-C and 32.77% top-1 accuracy on Stylized-ImageNet, building the new state-of-the-art. The code will be available at https://github.com/alibaba/easyrobust.Comment: Accepted to NeurIPS 2022, https://github.com/alibaba/easyrobus

Gigabit close-proximity wireless connections supported by 60 GHz RoF links with low carrier suppression

We present an experimental investigation of the 60 GHz optical carrier suppressed radio over fiber systems with less than 5 dB carrier suppression. As a case study, the 60 GHz RoF signal is generated using a 12.5 Gb/s commercially available Mach-Zehnder modulator biased at its minimum point. We report on error free transmission over 20 km of standard single mode fiber and 1 m of wireless distance. Furthermore, the efficiency of photonic RF generation depending on the value of carrier suppression is reported. We argue that transport of RoF signals with low carrier suppression assisted with simplified techniques of lightwave generation, baseband data modulation, and RF downconversion might be a promising enabling technology for fiber support of close-proximity wireless terminals

Nitrous oxide abuse in a 21-year-old female: a case report and review of literature

The abuse of nitrous oxide (N2O) poses a substantial public health challenge. In many countries, including China, regulations governing the utilization and accessibility to N2O remain ambiguous, particularly within the food industry. Here, we report a case of a 21-year-old female who presented with symptoms of subacute combined degeneration (SCD) of the spinal cord due to N2O abuse. The patient exhibited bilateral lower limb numbness and weakness, low serum vitamin B12 levels with elevated homocysteine levels, and lumbar spine magnetic resonance imaging (MRI) revealed abnormal signals of the spinal cord. Following cessation of N2O and comprehensive therapy including methylcobalamin and nerve growth factor, the symptoms significantly improved. A follow-up examination 3 months later showed good progress in gait stability. At a 5-year follow-up, the patient’s previous clinical symptoms had completely disappeared, and her quality of life had returned to normal. This case underscores the urgency of raising awareness and prevention of N2O abuse, emphasizing the importance of timely diagnosis and comprehensive treatment for patient recovery. Clear formulation and enforcement of relevant regulatory measures are equally crucial in reducing instances of abuse

A charging pricing strategy of electric vehicle fast charging stations for the voltage control of electricity distribution networks

With the increasing number of electric vehicles (EVs), the EV fast charging load will significantly affect the voltage quality of electricity distribution networks. On the other hand, EVs have potentials to change the choices of charging locations due to the incentives from the variations of charging prices, which can be considered as a flexible response resource for electricity distribution networks. In this paper, a charging pricing strategy of EV fast charging stations (FCSs) was developed to determine the pricing scheme for the voltage control of electricity distribution networks, which consisted of a simulation model of EV mobility and a double-layer optimization model. Considering the travel characteristics of users, the simulation model of EV mobility was developed to accurately determine the fast charging demand. Taking the total income of FCSs and the users’ response to the pricing scheme into account, the double-layer optimization model was developed to optimize the charging pricing scheme and minimize the total voltage magnitude deviation of distribution networks. A test case was used to verify the proposed strategy. The results show that the spatial distribution of EV fast charging loads was reallocated by the proposed charging pricing scheme. It can also be seen that the proposed strategy can make full use of the response capacity from EVs to improve the voltage profiles without decreasing the income of the FCSs

Metabolic response of Nile tilapia (Oreochromis niloticus) to acute and chronic hypoxia stress

© 2018 Elsevier BV. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 24 month embargo from date of publication (May 2018) in accordance with the publisher’s archiving policy.Hypoxia is a critical issue in aquaculture especially in intensive aquaculture systems. Acute hypoxia stress with dissolved oxygen (DO) 0.7±0.1 mg/L for 6 h and chronic hypoxia stress with DO 1.1±0.1 mg/L for 4 weeks were used to investigate the response of nutritional metabolic pathways in Nile tilapia Oreochromis niloticus. Fish in the acute and chronic experiments had different adaptive mechanisms. Upon acute hypoxia stress, the contents of liver glycogen and muscle glycogen were significantly lower, but there was no significant difference in triglycerides (TG). The lactate dehydrogenase (LDH) activities increased after exposure to acute hypoxia stress. The mRNA expression of genes involved in glycolysis and glycogenolysis was significantly up-regulated by acute hypoxia stress. However, the response of fish to long-term hypoxia stress was different from acute hypoxia. Compared with the normoxia treatment, the crude fat in fish decreased in the hypoxia group and TG in the liver and muscle were significantly lower. Beta oxidation of the liver was enhanced in the hypoxia group, while the hepatic glycogen content increased in the hypoxia group. Transcriptomic analysis showed that the expression of genes related to carbohydrate synthesis and lipolysis increased in the hypoxia group, while genes related to carbohydrate catabolism and fat synthesis showed the opposite. This study indicates that fish could utilize carbohydrate as a main energy source during acute hypoxia stress, and metabolize more lipid during long-term hypoxia stress. A high carbohydrate content in the diet may help reduce negative effects from acute hypoxia stress, and an appropriate increase of fat content in the diet may benefit fish growth in a hypoxia environment, e.g., in high-density aquaculture ponds