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Ovarian and breast cancer are prevalent female malignancies with increasing occurrence incidence and metastasis, significantly affecting the health and life quality of women globally. Anesthetic lidocaine has presented anti-tumor activities in the experimental conditions. However, the effect of lidocaine on ovarian and breast cancer remains elusive. We identified the important function of lidocaine in enhancing ferroptosis and repressing progression of ovarian and breast cancer. Our data showed that lidocaine further repressed erastin-inhibited ovarian and breast cancer cell viabilities. The treatment of lidocaine induced accumulation of Fe 2+ , iron and lipid reactive oxygen species (ROS) in ovarian and breast cancer cells. The ovarian and breast cancer cell proliferation was suppressed while cell apoptosis was induced by lidocaine in vitro . Lidocaine attenuated invasion and migration of ovarian and breast cancer cells as well. Regarding the mechanism, we found that lidocaine downregulated solute carrier family 7 member 11 (SLC7A11) expression by enhancing microRNA-382-5p (miR-382-5p) in the cells. The inhibition of miR-382-5p blocked lidocaine-induced ferroptosis of ovarian and breast cancer cells. MiR-382-5p/SLC7A11 axis was involved in lidocaine-mediated inhibition of ovarian and breast cancer cell proliferation in vitro . The miR-382-5p expression was down-regulated but SLC7A11 expression was up-regulated in clinical ovarian and breast cancer samples. Furthermore, the treatment of lidocaine repressed tumor growth of ovarian cancer cells in vivo , in which the miR-382-5p expression was increased while SLC7A11 expression was decreased. Consequently, we concluded that the lidocaine promoted ferroptosis by miR-382-5p/SLC7A11 axis in ovarian and breast cancer cells. The clinical value of lidocaine in the treatment of ovarian and breast cancer deserves to be proved in detail.

The integration of deep learning, particularly AI-Generated Content, with high-quality data derived from ab initio calculations has emerged as a promising avenue for transforming the landscape of scientific research. However, the challenge of designing molecular drugs or materials that incorporate multi-modality prior knowledge remains a critical and complex undertaking. Specifically, achieving a practical molecular design necessitates not only meeting the diversity requirements but also addressing structural and textural constraints with various symmetries outlined by domain experts. In this article, we present an innovative approach to tackle this inverse design problem by formulating it as a multi-modality guidance optimization task. Our proposed solution involves a textural-structure alignment symmetric diffusion framework for the implementation of molecular optimization tasks, namely 3DToMolo. 3DToMolo aims to harmonize diverse modalities including textual description features and graph structural features, aligning them seamlessly to produce molecular structures adhere to specified symmetric structural and textural constraints by experts in the field. Experimental trials across three guidance optimization settings have shown a superior hit optimization performance compared to state-of-the-art methodologies. Moreover, 3DToMolo demonstrates the capability to discover potential novel molecules, incorporating specified target substructures, without the need for prior knowledge. This work not only holds general significance for the advancement of deep learning methodologies but also paves the way for a transformative shift in molecular design strategies. 3DToMolo creates opportunities for a more nuanced and effective exploration of the vast chemical space, opening new frontiers in the development of molecular entities with tailored properties and functionalities.

Electrocatalysis, as the nexus for energy storage and environmental remediation, requires developing low-cost and high-performing heterogeneous catalysts. Compared with the single atom catalysts (SACs), dual-atom catalysts (DACs) are attracting ever-increasing interest due to their higher metal loading, more versatile active sites and unique reactivity. However, controlled synthesis of DACs remains a great challenge, and their electrocatalytic applications are still in infancy. This review first discusses the synthesis of DACs by highlighting several synthetic strategies. Subsequently, we exemplify the unique reactivities of DACs in electrocatalytic applications including water splitting, oxygen reduction, carbon dioxide reduction and nitrogen reduction. The structure-activity relations of DACs are specifically discussed in comparison with that of SACs, on the basis of experimental and theoretical studies. Finally, the opportunities and challenges of DACs are summarized in terms of rational design, controlled synthesis, characterization, and applications.

Metal–organic frameworks (MOFs) have been demonstrated to be desired candidates for sensing definite species owing to their tunable composition, framework structure and functionality. In this work, the NH2-MIL-101 series was utilized for sensing specific amino acids. The results show that cysteine (Cys) can significantly enhance the fluorescence emission of NH2-MIL-101-Fe suspended in water, while NH2-MIL-101-Al exhibits the ability to sense lysine (Lys), arginine (Arg) and histidine (His) in aqueous media via turn-on fluorescence emission. Titration experiments ensure that NH2-MIL-101-Fe and NH2-MIL-101-Al can selectively and quantitatively detect these amino acids. The sensing mechanism was examined and discussed. The results of this study show that the metal centers in MOFs are crucial for sensing specific amino acids.

Enveloped viruses encased within a lipid bilayer membrane are highly contagious and can cause many infectious diseases like influenza and COVID-19, thus calling for effective prevention and inactivation strategies. Here, we develop a diatomic iron nanozyme with lipoxidase-like (LOX-like) activity for the inactivation of enveloped virus. The diatomic iron sites can destruct the viral envelope via lipid peroxidation, thus displaying non-specific virucidal property. In contrast, natural LOX exhibits low antiviral performance, manifesting the advantage of nanozyme over the natural enzyme. Theoretical studies suggest that the Fe-O-Fe motif can match well the energy levels of Fe 2 minority β-spin d orbitals and pentadiene moiety π* orbitals, and thus significantly lower the activation barrier of cis , cis -1,4-pentadiene moiety in the vesicle membrane. We showcase that the diatomic iron nanozyme can be incorporated into air purifier to disinfect airborne flu virus. The present strategy promises a future application in comprehensive biosecurity control. Enveloped viruses encased within a lipid bilayer membrane are highly contagious and cause diseases like influenza and COVID-19, so strategies for their prevention and inactivation are needed. Here, the authors develop a diatomic iron nanozyme with lipoxidase-like activity for the inactivation of enveloped viruses, where the diatomic iron sites destroy the viral envelope via lipid peroxidation.

Background While it is known that klotho has negative regulatory effects in a variety of diseases such as metabolic disorders and kidney disease, the specific role of klotho in rheumatoid arthritis (RA) and its effect on mortality are unclear. This study investigated the association between serum klotho levels and mortality in patients with RA. Methods This study included 841 adults with RA from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016 to extract the concentrations of serum klotho. The association between klotho and RA was determined using Cox regression, Kaplan–Meier (KM) curves, and restricted cubic spline (RCS) models. Results A total of 841 patients with RA were included in this study, who were divided into four groups based on the quartiles of serum klotho levels (Q1, Q2, Q3, and Q4). Cox regression analysis with adjustment for covariates revealed that high levels of klotho lowered the risk of both all-cause and cardiovascular mortality compared to the Q1 group. The KM curve analysis suggested that this effect was more pronounced for all-cause mortality. The RCS-fitted Cox regression model indicated a U-shaped correlation between serum klotho levels and RA mortality. The risk of all-cause mortality increased with decreasing serum klotho levels below a threshold of 838.81 pg/mL. Subgroup analysis revealed that the protective effect of klotho was more pronounced in patients with the following characteristics: male, white ethnicity, age ≥ 60 years, body mass index < 25 kg/m 2 , estimated glomerular filtration rate ≥ 60 mL/ (min × 1.73 m 2 ), and 25-hydroxyvitamin D level ≥ 50 nmol/L. Conclusion Serum klotho levels had a U-shaped correlation with all-cause mortality in patients with RA, indicating that maintain a certain level of serum klotho could prevent premature death.