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Neuromyelitis optica spectrum disorders (NMOSDs) are most common in anti-aquaporin 4 (AQP4) antibody positive NMOSDs, which are characterized by recurrent episodes of optic neuritis and myelitis, etc., and severely reduce the quality of life. In recent years, new insights into the diagnostic techniques, diagonstic markers, and immunotherapy of anti - AQP4 antibody positive NMOSDs have continued to emerge, and here we focus on synthesizing new advances in the diagnostic techniques and diagonstic markers of anti-AQP4 antibody positive NMOSDs and the most recent recommendations for its treatment, in hopes of summarizing to promote the understanding and application of new diagnostic and therapeutic techniques for anti-AQP4 antibody positive NMOSDs in China, and to explore more possible clinical diagnostic and therapeutic approaches.

Dyslipidemia is the most prevalent independent risk factor for patients with chronic kidney disease (CKD). Lipid-induced NLRP3 inflammasome activation in kidney-resident cells exacerbates renal injury by causing sterile inflammation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that modulates the cellular redox balance; however, the exact role of Nrf2 signaling and its regulation of the NLRP3 inflammasome in hyperlipidemia-induced kidney injury are poorly understood. In this study, we demonstrated that activation of the mtROS–NLRP3 inflammasome pathway is a critical contributor to renal tubular epithelial cell (RTEC) apoptosis under hyperlipidemia. In addition, the Nrf2/ARE signaling pathway is activated in renal tubular epithelial cells under hyperlipidemia conditions both in vivo and in vitro, and Nrf2 silencing accelerated palmitic acid (PA)-induced mtROS production, mitochondrial injury, and NLRP3 inflammasome activation. However, the activation of Nrf2 with tBHQ ameliorated mtROS production, mitochondrial injury, NLRP3 inflammasome activation, and cell apoptosis in PA-induced HK-2 cells and in the kidneys of HFD-induced obese rats. Furthermore, mechanistic studies showed that the potential mechanism of Nrf2-induced NLRP3 inflammasome inhibition involved reducing mtROS generation. Taken together, our results demonstrate that the Nrf2/ARE signaling pathway attenuates hyperlipidemia-induced renal injury through its antioxidative and anti-inflammatory effects through the downregulation of mtROS-mediated NLRP3 inflammasome activation.

Qiskit is one of the common quantum computing frameworks and and the qiskit-aer package can accelerating quantum circuit simulation using NVIDIA GPU with the help of THRUST. AMD ROCm framework similar to CUDA, a heterogeneous computing framework supporting both the NVIDIA and AMD GPUs provides the possibility to porting Qiskit/Qiskit-Aer from CUDA platform to its own. We present the porting progress of Qiskit/QiskitAer and preliminary performance test on both NVIDA and AMD GPUs. Our results show that Qiskit/Qiskit-Aer cand work well on AMD GPUs with the help of ROCm/HIP, and has comparable performance on AMD platform.

MICAL proteins represent a unique family of actin regulators crucial for synapse development, membrane trafficking, and cytokinesis. Unlike classical actin regulators, MICALs catalyze the oxidation of specific residues within actin filaments to induce robust filament disassembly. The potent activity of MICALs requires tight control to prevent extensive damage to actin cytoskeleton. However, the molecular mechanism governing MICALs' activity regulation remains elusive. Here, we report the cryo-EM structure of MICAL1 in the autoinhibited state, unveiling a head-to-tail interaction that allosterically blocks enzymatic activity. The structure also reveals the assembly of C-terminal domains via a tripartite interdomain interaction, stabilizing the inhibitory conformation of the RBD. Our structural, biochemical, and cellular analyses elucidate a multi-step mechanism to relieve MICAL1 autoinhibition in response to the dual-binding of two Rab effectors, revealing its intricate activity regulation mechanisms. Furthermore, our mutagenesis study of MICAL3 suggests the conserved autoinhibition and relief mechanisms among MICALs. This study reports the cryo-EM structure of full-length MICAL1 in its autoinhibited conformation, unveiling the molecular mechanisms of tail-mediated inhibition and Rab-binding-mediated relief that regulate MICAL's activity in F-actin disassembly. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is a common and aggressive primary malignancy worldwide. Dysregulation of long non-coding RNAs (lncRNAs) has been shown to play an essential regulatory role in multiple cancers. However, the role of PGM5-AS1 in NSCLC remains unclear. Here, we found that PGM5-AS1 was down-regulated in NSCLC tissues and cells. Furthermore, reduced PGM5-AS1 expression levels were associated with larger tumor size, positive lymph node metastasis, advanced TNM stage and worse prognosis. We found that overexpression of PGM5-AS1 inhibited cell proliferation and metastasis, and induced apoptosis and G0/G1 cell cycle arrest in NSCLC cell lines. Using dual luciferase gene reporter and RNA immunoprecipitation assays, we confirmed that miR-423-5p interacted with PGM5-AS1, and that their expression levels were negatively correlated in NSCLC tissues. miR-423-5p was also found to reverse PGM5-AS1-induced malignant biological behavior. Moreover, we identified slit guidance ligand 2 (SLIT2) as a target gene of miR-423-5p. Using a dual luciferase gene reporter assay, we confirmed the regulatory relationship between SLIT2 and miR-423-5p and demonstrated that their expression levels were negatively correlated. Our rescue experiments showed that SLIT2 knockdown reversed miR-423-5p-mediated effects. Overall, this study identifies PGM5-AS1 as a potential prognostic biomarker for NSCLC and shows that PGM5-AS1 suppresses NSCLC development by regulating the miR-423-5p/SLIT2 axis. [ABSTRACT FROM AUTHOR]

Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS), a prevalent urological ailment, exerts a profound influence upon the well‐being of the males. Autoimmunity driven by Th17 cells has been postulated as a potential factor in CP/CPPS pathogenesis. Nonetheless, elucidating the precise mechanisms governing Th17 cell recruitment to the prostate, triggering inflammation, remained an urgent inquiry. This study illuminated that CCL20 played a pivotal role in attracting Th17 cells to the prostate, thereby contributing to prostatitis development. Furthermore, it identified prostate stromal cells and immune cells as likely sources of CCL20. Additionally, this research unveiled that IL‐17A, released by Th17 cells, could stimulate macrophages to produce CCL20 through the NF‐κB/MAPK/PI3K pathway. The interplay between IL‐17A and CCL20 establishes a positive feedback loop, which might serve as a critical mechanism underpinning the development of chronic prostatitis, thus adding complexity to its treatment challenges. [ABSTRACT FROM AUTHOR]

Direct aging of water-quenched metastable β-titanium alloys usually follows the sequence: rapid growth of ωiso and then slow transformation into α. To inhibit ωiso growth and promote α nucleation, 6% pre-deformation was introduced in Ti-10V-6Cu alloy before 500°C/60s aging. An ultrafast α-formation and a few α-free kink-bands are observed, indicating the alteration of the precipitation sequence. For α-nucleation without ωiso as the sites, it shows that O' nanodomains induced by stress accumulation around slip bands mediate the ultrafast nucleation of hcp-α structure, while dislocation pipe diffusion accelerates the necessary phase separation. This provides new insights into regulating precipitation kinetics of age-hardenable β-titanium alloys. [ABSTRACT FROM AUTHOR]

Background and Aims Methods Results Conclusions Distinctive gut microbial profiles have been observed between patients with Wilson disease (WD) and healthy individuals. Despite this, the exact relationship and influence of gut microbiota on the advancement of WD‐related liver damage remain ambiguous. This research seeks to clarify the gut microbiota characteristics in both human patients and mouse models of WD, as well as their impact on liver injury.Gut microbial features in healthy individuals, patients with WD, healthy mice and mice with early‐ and late‐stage WD were analysed using 16S rRNA gene sequencing. Additionally, WD‐afflicted mice underwent treatment with either an antibiotic cocktail (with normal saline as a control) or healthy microbiota (using disease microbiota as a control). The study assessed gut microbiota composition, hepatic transcriptome profiles, liver copper concentrations and hepatic pathological injuries.Patients with hepatic WD and mice with WD‐related liver injury displayed altered gut microbiota composition, notably with a significant reduction in Lactobacillus abundance. Additionally, the abundances of several gut genera, including Lactobacillus, Veillonella and Eubacterium coprostanoligenes, showed significant correlations with the severity of liver injury in patients with WD. In WD mice, antibiotic treatment or transplantation of healthy microbiota altered the gut microbial structure, increased Lactobacillus abundance and modified the hepatic transcriptional profile. These interventions resulted in reduced hepatic copper concentration and alleviation of WD‐related liver injury.Individuals and mice with pronounced WD‐related liver injury exhibited shifts in gut microbial composition. Regulating gut microbiota through healthy microbiota transplantation emerges as a promising therapeutic approach for treating WD‐related liver injury. [ABSTRACT FROM AUTHOR]

Hypoxia, as a prominent feature of the tumor microenvironment, has a profound impact on the multicomponent changes within this environment. Under hypoxic conditions, the malignant phenotype of tumor cells, the variety of cell types within the tumor microenvironment, as well as intercellular communication and material exchange, undergo complex alterations. These changes provide significant prospects for exploring the mechanisms of tumor development under different microenvironmental conditions and for devising therapeutic strategies. Exosomes secreted by tumor cells and stromal cells are integral components of the tumor microenvironment, serving as crucial mediators of intercellular communication and material exchange, and have consequently garnered increasing attention from researchers. This review focuses on the mechanisms by which hypoxic conditions promote the release of exosomes by tumor cells and alter their encapsulated contents. It also examines the effects of exosomes derived from tumor cells, immune cells, and other cell types under hypoxic conditions on the tumor microenvironment. Additionally, we summarize current research progress on the potential clinical applications of exosomes under hypoxic conditions and propose future research directions in this field., Competing Interests: These authors declare that they have no conflicts of interest in this work., (© 2024 Wang et al.)

Purpose: The purpose of this study is to investigate whether gene mutations can lead to the growth of malignant pulmonary nodules., Methods: Retrospective analysis was conducted on patients with pulmonary nodules at Hebei Provincial People's Hospital, collecting basic clinical information such as gender, age, BMI, and hematological indicators. According to the inclusion and exclusion criteria, 85 patients with malignant pulmonary nodules were selected for screening, and gene mutation testing was performed on all patient tissues to explore the relationship between gene mutations and the growth of malignant pulmonary nodules., Results: There is a correlation between KRAS and TP53 gene mutations and the growth of pulmonary nodules (P < 0.05), while there is a correlation between KRAS and TP53 gene mutations and the growth of pulmonary nodules in the subgroup of invasive malignant pulmonary nodules (P < 0.05)., Conclusion: Mutations in the TP53 gene can lead to the growth of malignant pulmonary nodules and are correlated with the degree of invasion of malignant pulmonary nodules., (© 2024. The Author(s).)