Overcoming multiple barriers to deliver photo-gene system for glioma-targeted combined therapy.

Overcoming multiple barriers to deliver macromolecular drugs is an urgent challenge for glioma treatment. Herein, a strategy of protein corona-regulation synergizing with photoactivation based on T10 peptide-modified and indocyanine green (ICG)-loaded dendrigraft poly-L-lysines was proposed to augment prime editing therapy of glioma. First, the modified T10 peptide could escape the interference barrier of protein crown in blood via its specific binding with endogenous transferrin, thus crossing the blood-brain barrier (BBB) and achieving the targeting recognition of glioma cells. Next, the loaded ICG could weaken the tumor stromal barrier, decrease the cell membrane barrier and escape the lysosomal degradation/autophagy barrier via its photothermal and photodynamic effects. Subsequently, a therapeutic gene that could downregulate p-ERK1/2 for tumor growth inhibition and immunoregulation could be effectively delivered into the glioma cells. The glioma-targeted photo-gene combined immunotherapy effectively inhibit the glioma growth, especially co-dosing with the PD-1 antibody.

Moss-m7G: A Motif-Based Interpretable Deep Learning Method for RNA N7-Methlguanosine Site Prediction.

N-7methylguanosine (m7G) modification plays a crucial role in various biological processes and is closely associated with the development and progression of many cancers. Accurate identification of m7G modification sites is essential for understanding their regulatory mechanisms and advancing cancer therapy. Previous studies often suffered from insufficient research data, underutilization of motif information, and lack of interpretability. In this work, we designed a novel motif-based interpretable method for m7G modification site prediction, called Moss-m7G. This approach enables the analysis of RNA sequences from a motif-centric perspective. Our proposed word-detection module and motif-embedding module within Moss-m7G extract motif information from sequences, transforming the raw sequences from base-level into motif-level and generating embeddings for these motif sequences. Compared with base sequences, motif sequences contain richer contextual information, which is further analyzed and integrated through the Transformer model. We constructed a comprehensive m7G data set to implement the training and testing process to address the data insufficiency noted in prior research. Our experimental results affirm the effectiveness and superiority of Moss-m7G in predicting m7G modification sites. Moreover, the introduction of the word-detection module enhances the interpretability of the model, providing insights into the predictive mechanisms.

Fatigue in rheumatoid arthritis patients: The status, independent risk factors, and consistency of multiple scales.

INTRODUCTION: Fatigue is a common symptom that negatively affects the outcomes and functions of rheumatoid arthritis (RA) patients. This study aimed to assess the fatigue by two scales and validate their consistency, also to comprehensively evaluate fatigue-related risk factors in RA patients. METHODS: In this case-control study, the fatigue of 160 RA patients and 60 healthy controls was evaluated by the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ) and the Chinese version of the Brief Fatigue Inventory (BFI-C). The 28-joint disease activity score using erythrocyte sedimentation rate of RA patients was assessed. RESULTS: The BRAF-MDQ and BFI-C scores were elevated in RA patients versus healthy controls (all p < .001). Interestingly, BRAF-MDQ global fatigue score positively correlated with BFI-C global fatigue score in both RA patients (r = .669, p < .001) and healthy controls (r = .527, p < .001); meanwhile, Kendall's tau-b test showed a high consistency between BRAF-MDQ and BFI-C global fatigue scores in RA patients (W = 0.759, p < .001) and healthy controls (W = 0.933, p < .001). Notably, higher education level (В = -4.547; 95% confidence interval: -7.065, -2.029; p < .001) and swollen joint count (В = 1.965; 95% confidence interval: 1.375, 2.554; p < .001) independently related to BRAF-MDQ global fatigue score; higher education level (В = -0.613; 95% confidence interval: -0.956, -0.269; p = .001) and clinical disease activity index (В = 0.053; 95% confidence interval: 0.005, 0.102; p = .032) independently linked with BFI-C global fatigue score. CONCLUSION: Fatigue commonly occurs in RA patients, which independently relates to education level and disease activity. Furthermore, BRAF-MDQ and BFI-C scales exhibit a high consistency in assessing fatigue.

Adalimumab exhibits superiority over etanercept in terms of a numerically higher response rate and equivalent adverse events: A real-world finding.

INTRODUCTION: Adalimumab (ADA) and etanercept (ETN) are the most commonly applied biologics for rheumatoid arthritis (RA) management in China; however, the evidence regarding their superiority is controversial. In addition, in real-world clinical settings, many factors may affect the application of these agents, such as dosage and administration period. Therefore, the present real-world study aimed to compare the efficacy and safety of ADA and ETN treatment in RA patients via the propensity score matching method. METHODS: In total, 105 RA patients receiving ADA (n = 66) or ETN (n = 39) were reviewed in this retrospective study. The propensity score matching method was used to eliminate discrepancies in baseline features. Clinical response, low disease activity (LDA), and remission were evaluated based on the DAS28. RESULTS: Before propensity score matching, compared with ETN, ADA yielded higher rates of clinical response at W24 (97.0% vs. 84.6%, p = .021), LDA at W12 (78.8% vs. 51.3%, p = .003), and remission at W24 (75.8% vs. 46.2%, p = .002). After propensity score matching, compared with ETN, ADA only achieved a higher rate of clinical response at W24 (96.3% vs. 77.8%, p = .043), whereas the rates of LDA and remission were not different between ADA and ETN treatments at any time point (all p > .05). In addition, the incidence of adverse events was not significantly different between the ADA and ETN treatments (all p > .05). CONCLUSION: ADA shows superiority over ETN in terms of a numerically greater response rate and equivalent adverse events.

Anxiety and depression in rheumatoid arthritis patients: prevalence, risk factors and consistency between the Hospital Anxiety and Depression Scale and Zung's Self-rating Anxiety Scale/Depression Scale.

Objectives: The aim was to explore the prevalence and independent risk factors for anxiety and depression in RA patients and to assess the consistency between the hospital anxiety and depression scale (HADS) and Zung's self-rating anxiety scale/depression scale (SAS/SDS). Methods: In total, 160 RA patients and 60 healthy controls (HCs) were enrolled consecutively, and HADS and SAS/SDS were completed. Results: The HADS-defined anxiety rate, HADS-defined depression rate, SAS-defined anxiety rate and SDS-defined depression rate were 36.9, 36.3, 29.4 and 29.4%, respectively, in RA patients, all of which were much higher in RA patients than in HCs (all P < 0.001). A relatively high consistency was observed between HADS-defined anxiety and SAS-defined anxiety (κ = 0.551, P < 0.001) and between HADS-defined depression and SDS-defined depression (κ = 0.563, P < 0.001) in RA patients. Interestingly, screened by multivariate logistic regression analyses, single/divorced/widowed marital status, swollen joint count, disease duration, ESR, physician's global assessment (PhGA) and DAS28 were independently correlated with HADS-defined or SAS-defined anxiety risk in RA patients; meanwhile, female biological sex, single/divorced/widowed marital status, rural location, disease duration, PhGA and DAS28 were independently associated with HADS-defined or SDS-defined depression risk in RA patients. Conclusion: Anxiety and depression are highly prevalent in RA patients and are independently correlated with single/divorced/widowed marital status and higher disease activity. In addition, the HADS presents a high consistency with the SAS/SDS with many fewer questions, which might be more suitable for long-term assessment of RA.

FBLPF-ABOW: An Effective Method for Blink Artifact Removal in Single-Channel EEG Signal.

OBJECTIVE: The latest development in low-cost single-channel Electroencephalography (EEG) devices is gaining widespread attention because it reduces hardware complexity. Discrete wavelet transform (DWT) has been a popular solution to eliminate the blink artifacts in EEG signals. However, the existing DWT-based methods share the same wavelet function among subjects, which ignores the individual difference. To remedy this deficiency, this article proposes a novel approach to eliminate the blink artifacts in single-channel EEG signals. METHODS: Firstly, the forward-backward low-pass filter (FBLPF) and a fixed-length window are used to detect blink artifact intervals. Secondly, the adaptive bi-orthogonal wavelet (ABOW) is constructed based on the most representative blink signal. Thirdly, these detected signals are filtered by ABOW-DWT. The DWT's decomposition depth is automatically chosen by a similarity-based method. RESULTS: Compared to eight state-of-the-art methods, experiments on semi-simulated and real EEG signals demonstrate the proposed method's superiority in removing the blink artifacts with less neural information loss. SIGNIFICANCE: To filter the blink artifacts in single-channel EEG signals, the innovative idea of constructing an adaptive wavelet function based on the signal characteristics rather than using the conventional wavelet is proposed for the first time.

Diabetes mellitus promotes susceptibility to periodontitis-novel insight into the molecular mechanisms.

Diabetes mellitus is a main risk factor for periodontitis, but until now, the underlying molecular mechanisms remain unclear. Diabetes can increase the pathogenicity of the periodontal microbiota and the inflammatory/host immune response of the periodontium. Hyperglycemia induces reactive oxygen species (ROS) production and enhances oxidative stress (OS), exacerbating periodontal tissue destruction. Furthermore, the alveolar bone resorption damage and the epigenetic changes in periodontal tissue induced by diabetes may also contribute to periodontitis. We will review the latest clinical data on the evidence of diabetes promoting the susceptibility of periodontitis from epidemiological, molecular mechanistic, and potential therapeutic targets and discuss the possible molecular mechanistic targets, focusing in particular on novel data on inflammatory/host immune response and OS. Understanding the intertwined pathogenesis of diabetes mellitus and periodontitis can explain the cross-interference between endocrine metabolic and inflammatory diseases better, provide a theoretical basis for new systemic holistic treatment, and promote interprofessional collaboration between endocrine physicians and dentists.

Construction of Core-Shell NiMoO4@Ni-Co-S Nanorods as Advanced Electrodes for High-Performance Asymmetric Supercapacitors.

In this work, hierarchical core-shell NiMoO4@Ni-Co-S nanorods were first successfully grown on nickel foam by a facile two-step method to fabricate a bind-free electrode. The well-aligned electrode wrapped by Ni-Co-S nanosheets displays excellent nanostructural properties and outstanding electrochemical performance, owing to the synergistic effects of both nickel molybdenum oxides and nickel cobalt sulfides. The prepared core-shell nanorods in a three-electrode cell yielded a high specific capacitance of 2.27 F cm-2 (1892 F g-1) at a current density of 5 mA cm-2 and retained 91.7% of the specific capacitance even after 6000 cycles. Their electrochemical performance was further investigated for their use as positive electrode for asymmetric supercapacitors. Notably, the energy density of the asymmetric supercapacitor device reached 2.45 mWh cm-3 at a power density of 0.131 W cm-3, and still retained a remarkable 80.3% of the specific capacitance after 3500 cycles. There is great potential for the electrode composed of the core-shell NiMoO4@Ni-Co-S nanorods for use in an all-solid-state asymmetric supercapacitor device.