The deubiquitinating enzyme USP35 regulates the stability of NRF2 protein.

Many cancers exhibit resistance to chemotherapy, resulting in a poor prognosis. The transcription factor NRF2, activated in response to cellular antioxidants, plays a crucial role in cell survival, proliferation, and resistance to chemotherapy. This factor may serve as a promising target for therapeutic interventions in esophageal carcinoma. Recent research suggests that NRF2 activity is modulated by ubiquitination mediated by the KEAP1-CUL3 E3 ligase complex, highlighting the importance of deubiquitination. However, the specific deubiquitinase responsible for regulating NRF2 in esophageal cancer remains unknown. In this study, a novel regulator of the NRF2 protein, Ubiquitin-Specific Protease 35 (USP35), has been identified. Mechanistically, USP35 modulates NRF2 stability through enzymatic deubiquitination. USP35 interacts with NRF2 and facilitates its deubiquitination. Knockdown of USP35 leads to a notable increase in NRF2 levels and enhances the sensitivity of cells to chemotherapy. These findings suggest that the USP35-NRF2 axis is a key player in the regulation of therapeutic strategies for esophageal cancer.

Comparative genomic and phylogenetic analyses of mitochondrial genomes of hawthorn (Crataegus spp.) in Northeast China.

Hawthorn (Crataegus spp.) plants are major sources of health food and medicines. Twenty species and seven variations of Crataegus are present in China. A variety of unique Crataegus species was found in their natural distribution in northeast China. In the present study, we assembled and annotated the mitochondrial genomes of five Crataegus species from northeastern China. The sizes of the newly sequenced mitochondrial genomes ranged from 245,907 bp to 410,837 bp. A total of 45-55 genes, including 12-19 transfer RNA genes, three ribosomal RNA genes, and 29-33 protein-coding genes (PCGs) were encoded by these mitochondrial genomes. Seven divergent hotspot regions were identified by comparative analyses: atp6, nad3, ccmFN, matR, nad1, nad5, and rps1. The most conserved genes among the Crataegus species, according to the whole-genome correlation analysis, were nad1, matR, nad5, ccmFN, cox1, nad4, trnQ-TTG, trnK-TTT, trnE-TTC, and trnM-CAT. Horizontal gene transfer between organellar genomes was common in Crataegus plants. Based on the phylogenetic trees of mitochondrial PCGs, C. maximowiczii, C. maximowiczii var. ninganensis, and C. bretschneideri shared similar maternal relationships. This study improves Crataegus mitochondrial genome resources and offers important insights into the taxonomy and species identification of this genus.

SecureNet: Proactive intellectual property protection and model security defense for DNNs based on backdoor learning.

With the widespread application of deep neural networks (DNNs), the risk of privacy breaches against DNN models is constantly on the rise, resulting in an increasing need for intellectual property (IP) protection for such models. Although neural network watermarking techniques are widely used to safeguard the IP of DNNs, they can only achieve passive protection and cannot actively prevent unauthorized users from illicit use or embezzlement of the trained DNN models. Therefore, the development of proactive protection techniques to prevent IP infringement is imperative. To this end, we propose SecureNet, a key-based access license framework for DNN models. The proposed approach involves injecting license keys into the model through backdoor learning, enabling correct model functionality only when the appropriate license key is included in the input. To ensure the reusability of DNN models, we also propose a license key replacement algorithm. In addition, based on SecureNet, we designed defense mechanisms against adversarial attacks and backdoor attacks, respectively. Furthermore, we introduce a fine-grained authorization method that enables flexible granting of model permissions to different users. We have designed four license-key schemes with different privileges, tailored to various scenarios. We evaluated SecureNet on five benchmark datasets including MNIST, Cifar10, Cifar100, FaceScrub, and CelebA, and assessed its performance on six classic DNN models: LeNet-5, VGG16, ResNet18, ResNet101, NFNet-F5, and MobileNetV3. The results demonstrate that our approach outperforms the state-of-the-art model parameter encryption methods by at least 95% in terms of computational efficiency. Additionally, it provides effective defense against adversarial attacks and backdoor attacks without compromising the model's overall performance.

Zhuifeng Tougu capsules in the treatment of knee osteoarthritis (cold dampness obstruction syndrome): a randomized, double blind, multicenter clinical study.

BACKGROUND: In Traditional Chinese Medicine (TCM) theory, cold dampness obstruction is one of the common syndromes of osteoarthritis. Therefore, in clinical practice, the main treatment methods are to dispel wind, remove dampness, and dissipate cold, used to treat knee osteoarthritis (KOA). This report describes a mulitercenter clinical study to assess Zhuifeng Tougu Capsule's efficacy and safety in the treatment of patients who are cold dampness obstruction syndrome in KOA, and to provide evidence-based medical for the rational use of Zhuifeng Tougu Capsules in clinical practice. METHODS: This randomized, parallel group controlled, double-blind, double dummy trial will include a total of 215 KOA patients who meet the study criteria. 215 patients underwent 1:1 randomisation, with 107 cases assigned the experimental group (Zhuifeng Tougu Capsules + Glucosamine Sulfate Capsules Simulator) and 108 assigned the control group (Glucosamine Sulfate Capsules + Zhuifeng Tougu Capsules Simulator). After enrolment, patients received 12 weeks of treatment. The main efficacy measure is the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain score. Visual analogue scale (VAS) pain score, Self-condition assessment VAS score, WOMAC KOA score, TCM syndrome score and TCM syndrome efficacy, ESR level, CRP level, suprapatellar bursa effusion depth, use of rescue drugs, and safety indicators are secondary efficacy indicators. RESULTS: Compared with before treatment, WOMAC pain score, VAS pain score, Self-condition assessment VAS score, WOMAC KOA score, and TCM syndrome score decreased significantly in both groups (P < 0.01). Also, the experimental group showed significant differences in the above indicators compared to control (P < 0.01). However, after treatment, no significant differences were showed in the ESR level, CRP level, and suprapatellar bursa effusion depth between the two groups (P > 0.05). No any serious adverse effects showed in the experimental group and control group. CONCLUSIONS: Zhuifeng Tougu Capsules can effectively improve knee joint function and significantly alleviate the pain of KOA. TRIAL REGISTRATION: Clinical trial registration was completed with the China Clinical Trial Registration Center for this research protocol (No. ChiCTR2000028750) on January 2, 2020.