Lithium Orbital Hybridization Chemistry to Stimulate Oxygen Redox with Reversible Phase Evolution in Sodium-Layered Oxide Cathodes.

Searching for high energy-density electrode materials for sodium ion batteries has revealed Na-deficient intercalation compounds with lattice oxygen redox as promising high-capacity cathodes. However, anionic redox reactions commonly encountered poor electrochemical reversibility and unfavorable structural transformations during dynamic (de)sodiation processes. To address this issue, we employed lithium orbital hybridization chemistry to create Na-O-Li configuration in a prototype P2-layered Na43/60Li1/20Mg7/60Cu1/6Mn2/3O2 (P2-NaLMCM') cathode material. That Li+ ions, having low electronegativity, reside in the transition metal slabs serves to stimulate unhybridized O 2p orbitals to facilitate the stable capacity contribution of oxygen redox at high state of charge. The prismatic-type structure evolving to an intergrowth structure of the Z phase at high charging state could be simultaneously alleviated by reducing the electrostatic repulsion of O-O layers. As a consequence, P2-NaLMCM' delivers a high specific capacity of 183.8 mAh g-1 at 0.05 C and good cycling stability with a capacity retention of 80.2% over 200 cycles within the voltage range of 2.0-4.5 V. Our findings provide new insights into both tailoring oxygen redox chemistry and stabilizing dynamic structural evolution for high-energy battery cathode materials.

Vertically Fluorinated Graphene Encapsulated SiOx Anode for Enhanced Li+ Transport and Interfacial Stability in High-Energy-Density Lithium Batteries.

Achieving high energy density has always been the goal of lithium-ion batteries (LIBs). SiOx has emerged as a compelling candidate for use as a negative electrode material due to its remarkable capacity. However, the huge volume expansion and the unstable electrode interface during (de)lithiation, hinder its further development. Herein, we report a facile strategy for the synthesis of surface fluorinated SiOx (SiOx@vG-F), and investigate their influences on battery performance. Systematic experiments investigations indicate that the reaction between Li+ and fluorine groups promotes the in-situ formation of stable LiF-rich solid electrolyte interface (SEI) on the surface of SiOx@vG-F anode, which effectively suppresses the pulverization of microsized SiOx particles during the charge and discharge cycle. As a result, the SiOx@vG-F enabled a higher capacity retention of 86.4% over 200 cycles at 1.0 C in the SiOx@vG-F||LiNi0.8Co0.1Mn0.1O2 full cell. This approach will provide insights for the advancement of alternative electrode materials in diverse energy conversion and storage systems.

Protein multi-level structure feature-integrated deep learning method for mutational effect prediction.

Through iterative rounds of mutation and selection, proteins can be engineered to enhance their desired biological functions. Nevertheless, identifying optimal mutation sites for directed evolution remains challenging due to the vastness of the protein sequence landscape and the epistatic mutational effects across residues. To address this challenge, we introduce MLSmut, a deep learning-based approach that leverages multi-level structural features of proteins. MLSmut extracts salient information from protein co-evolution, sequence semantics, and geometric features to predict the mutational effect. Extensive benchmark evaluations on 10 single-site and two multi-site deep mutation scanning datasets demonstrate that MLSmut surpasses existing methods in predicting mutational outcomes. To overcome the limited training data availability, we employ a two-stage training strategy: initial coarse-tuning on a large corpus of unlabeled protein data followed by fine-tuning on a curated dataset of 40-100 experimental measurements. This approach enables our model to achieve satisfactory performance on downstream protein prediction tasks. Importantly, our model holds the potential to predict the mutational effects of any protein sequence. Collectively, these findings suggest that our approach can substantially reduce the reliance on laborious wet lab experiments and deepen our understanding of the intricate relationships between mutations and protein function.

Highly reflective silver mirror enhanced by several dielectric films prepared under the low substrate temperature.

Optical paths in telescopes frequently incorporate silver mirrors for high sensitivity. Unfortunately, silver mirrors without protective coatings are susceptible to sulfurization and oxidation, compromising their quality. Even with protective layers, insufficient adhesion between the coating and the silver film can lead to peeling, exposing the silver to external environments and affecting its quality. This study aimed to identify dielectric materials with superior adhesion to silver, rendering them ideal choices for silver coating applications. By electron gun evaporation, different dielectric layers were deposited on the top and bottom of the silver film under a substrate temperature below 150 °C. These coatings were composed of materials with desired refractive indices, including aluminum oxide (Al2O3), aluminum-doped silicon, magnesium fluoride (MgF2), and other dielectrics. Following the deposition, a tape adhesion test was conducted to evaluate the bond strength of the samples. X-ray photoelectron spectroscopy (XPS) analysis was carried out to investigate the interaction between silver and its neighboring layers. The results revealed that Al2O3 and MgF2 exhibited exceptional adhesion to silver. Moreover, these multilayer coatings can effectively enhance the reflectance of silver in the visible (VIS) wavelength ranges.

Dissolved Black Carbon Facilitates the Photodegradation of Microplastics via Molecular Weight-Dependent Generation of Reactive Intermediates.

Photodegradation of microplastics (MPs) induced by sunlight plays a crucial role in determining their transport, fate, and impacts in aquatic environments. Dissolved black carbon (DBC), originating from pyrolyzed carbon, can potentially mediate the photodegradation of MPs owing to its potent photosensitization capacity. This study examined the impact of pyrolyzed wood derived DBC (5 mg C/L) on the photodegradation of polystyrene (PS) MPs in aquatic solutions under UV radiation. It revealed that the photodegradation of PS MPs primarily occurred at the benzene ring rather than the aliphatic segments due to the fast attack of hydroxyl radical (•OH) and singlet oxygen (1O2) on the benzene ring. The photosensitivity of DBC accelerated the degradation of PS MPs, primarily attributed to the increased production of •OH, 1O2, and triplet-excited state DBC (3DBC*). Notably, DBC-mediated photodegradation was related to its molecular weight (MW) and chemical properties. Low MW DBC (<3 kDa) containing more carbonyl groups generated more •OH and 1O2, accelerating the photodegradation of MPs. Nevertheless, higher aromatic phenols in high MW DBC (>30 kDa) scavenged •OH and generated more O2•-, inhibiting the photodegradation of MPs. Overall, this study offered valuable insights into UV-induced photodegradation of MPs and highlighted potential impacts of DBC on the transformation of MPs.

Trafficking circuit of CD8+ T cells between the intestine and bone marrow governs antitumour immunity.

Immunotherapy elicits a systemic antitumour immune response in peripheral circulating T cells. However, the T cell trafficking circuit between organs and their contributions to antitumour immunity remain largely unknown. Here we show in multiple mouse leukaemia models that high infiltration of leukaemic cells in bone marrow (BM) stimulates the transition of CD8+CD44+CD62L+ central memory T cells into CD8+CD44-CD62L- T cells, designated as inter-organ migratory T cells (TIM cells). TIM cells move from the BM to the intestine by upregulating integrin ß7 and downregulating C-X-C motif chemokine receptor 3 during leukaemogenesis. Upon immunogenic chemotherapy, these BM-derived TIM cells return from the intestine to the BM through integrin α4-vascular cell adhesion molecule 1 interaction. Blocking C-X-C motif chemokine receptor 3 function boosts the immune response against leukaemia by enhancing T cell trafficking. This phenomenon can also be observed in patients with leukaemia. In summary, we identify an unrecognized intestine-BM trafficking circuit of T cells that contributes to the antitumour effects of immunogenic chemotherapy.

Ursodeoxycholic acid and COVID-19 outcomes: a cohort study and data synthesis of state-of-art evidence.

BACKGROUND: The potential of ursodeoxycholic acid (UDCA) in inhibiting angiotensin-converting enzyme 2 was demonstrated. However, conflicting evidence emerged regarding the association between UDCA and COVID-19 outcomes, prompting the need for a comprehensive investigation. RESEARCH DESIGN AND METHODS: Patients diagnosed with COVID-19 infection were retrospectively analyzed and divided into two groups: the UDCA-treated group and the control group. Kaplan-Meier recovery analysis and Cox proportional hazards models were used to evaluate the recovery time and hazard ratios. Additionally, study-level pooled analyses for multiple clinical outcomes were performed. RESULTS: In the 115-patient cohort, UDCA treatment was significantly associated with a reduced recovery time. The subgroup analysis suggests that the 300 mg subgroup had a significant (adjusted hazard ratio: 1.63 [95% CI, 1.01 to 2.60]) benefit with a shorter duration of fever. The results of pooled analyses also show that UDCA treatment can significantly reduce the incidence of severe/critical diseases in COVID-19 (adjusted odds ratio: 0.68 [95% CI, 0.50 to 0.94]). CONCLUSIONS: UDCA treatment notably improves the recovery time following an Omicron strain infection without observed safety concerns. These promising results advocate for UDCA as a viable treatment for COVID-19, paving the way for further large-scale and prospective research to explore the full potential of UDCA.

Fine and combinatorial regulation of key metabolic pathway for enhanced ß-alanine biosynthesis with non-inducible Escherichia coli.

ß-Alanine is the only ß-amino acid in nature and one of the most important three-carbon chemicals. This work was aimed to construct a non-inducible ß-alanine producer with enhanced metabolic flux towards ß-alanine biosynthesis in Escherichia coli. First of all, the assembled E. coli endogenous promoters and 5'-untranslated regions (PUTR) were screened to finely regulate the combinatorial expression of genes panDBS and aspBCG for an optimal flux match between two key pathways. Subsequently, additional copies of key genes (panDBS K104S and ppc) were chromosomally introduced into the host A1. On these bases, dynamical regulation of the gene thrA was performed to reduce the carbon flux directed in the competitive pathway. Finally, the ß-alanine titer reached 10.25 g/L by strain A14-R15, 361.7% higher than that of the original strain. Under fed-batch fermentation in a 5-L fermentor, a titer of 57.13 g/L ß-alanine was achieved at 80 h. This is the highest titer of ß-alanine production ever reported using non-inducible engineered E. coli. This metabolic modification strategy for optimal carbon flux distribution developed in this work could also be used for the production of various metabolic products.

Effect of Mn on Cd2+ uptake by protoplasts of the Cd/Mn hyperaccumulator Celosia argentea Linn. differs by treatment method.

The effect mechanism of Mn on Cd uptake by Celosia argentea was investigated via a series of hydroponics experiments. The results showed that different manganese treatments had different effects on Cd uptake by C. argentea. Mn pretreatment increased Cd uptake by root protoplasts at Cd concentrations (4 and 6 µM). Protoplasts reached peak Cd uptake rate at 6 µM Cd and 25 °C, with 67.71 ± 0.13 µM h-1 mL-1 in the control, and 77.99 ± 0.49 µM h-1 mL-1 in the 50 µM Mn pretreatment group. However, simultaneous treatment with Cd and Mn reduced the Cd2+ uptake by root protoplasts. This discrepancy may be attributed to the fact that cadmium and manganese share some transporters in root cells. The transcriptome analysis in roots revealed that ten genes (including ABCC, ABCA, ABCG, ABCB, ABC1, BZIP19, and ZIP5) were significantly upregulated in response to Mn stress (p < 0.05). These genes regulate the expression of transporters belonging to the ABC, and ZIP families, which may be involved in Cd uptake by root cells of C. argentea. Mn pretreatment upregulates the expression of Mn/Cd transporters, enhancing Cd uptake by root protoplasts. For the simultaneous treatment of Cd and Mn, inhibition of Cd uptake was due to the competition of the same transporters. These findings provide helpful insights for understanding the mechanism of Mn and Cd uptake in hyperaccumulators and give implications to improve the phytoremediation of Cd-contaminated soil by C. argentea.

Through virtual saturation mutagenesis and rational design for superior substrate conversion in engineered d-amino acid oxidase.

The d-amino acid oxidase (DAAO) is pivotal in obtaining optically pure l-glufosinate (l-PPT) by converting d-glufosinate (d-PPT) to its deamination product. We screened and designed a Rasamsonia emersonii DAAO (ReDAAO), making it more suitable for oxidizing d-PPT. Using Caver 3.0, we delineated three substrate binding pockets and, via alanine scanning, identified nearby key residues. Pinpointing key residues influencing activity, we applied virtual saturation mutagenesis (VSM), and experimentally validated mutants which reduced substrate binding energy. Analysis of positive mutants revealed elongated side-chain prevalence in substrate binding pocket periphery. Although computer-aided approaches can rapidly identify advantageous mutants and guide further design, the mutations obtained in the first round may not be suitable for combination with other advantageous mutations. Therefore, each round of combination requires reasonable iteration. Employing VSM-assisted screening multiple times and after four rounds of combining mutations, we ultimately obtained a mutant, N53V/F57Q/V94R/V242R, resulting in a mutant with a 5097% increase in enzyme activity compared to the wild type. It provides valuable insights into the structural determinants of enzyme activity and introduces a novel rational design procedure.

Sodium layered oxide cathodes: properties, practicality and prospects.

Rechargeable sodium-ion batteries (SIBs) have emerged as an advanced electrochemical energy storage technology with potential to alleviate the dependence on lithium resources. Similar to Li-ion batteries, the cathode materials play a decisive role in the cost and energy output of SIBs. Among various cathode materials, Na layered transition-metal (TM) oxides have become an appealing choice owing to their facile synthesis, high Na storage capacity/voltage that are suitable for use in high-energy SIBs, and high adaptivity to the large-scale manufacture of Li layered oxide analogues. However, going from the lab to the market, the practical use of Na layered oxide cathodes is limited by the ambiguous understanding of the fundamental structure-performance correlation of cathode materials and lack of customized material design strategies to meet the diverse demands in practical storage applications. In this review, we attempt to clarify the fundamental misunderstandings by elaborating the correlations between the electron configuration of the critical capacity-contributing elements (e.g., TM cations and oxygen anion) in oxides and their influence on the Na (de)intercalation (electro)chemistry and storage properties of the cathode. Subsequently, we discuss the issues that hinder the practical use of layered oxide cathodes, their origins and the corresponding strategies to address their issues and accelerate the target-oriented research and development of cathode materials. Finally, we discuss several new Na layered cathode materials that show prospects for next-generation SIBs, including layered oxides with anion redox and high entropy and highlight the use of layered oxides as cathodes for solid-state SIBs with higher energy and safety. In summary, we aim to offer insights into the rational design of high-performance Na layered oxide cathode materials towards the practical realization of sustainable electrochemical energy storage at a low cost.

Quantification of Charge Transport and Mass Deprivation in Solid Electrolyte Interphase for Kinetically-Stable Low-Temperature Lithium-Ion Batteries.

Graphite (Gr)-based lithium-ion batteries with admirable electrochemical performance below -20 °C are desired but are hindered by sluggish interfacial charge transport and desolvation process. Li salt dissociation via Li+-solvent interaction enables mobile Li+ liberation and contributes to bulk ion transport, while is contradictory to fast interfacial desolvation. Designing kinetically-stable solid electrolyte interphase (SEI) without compromising strong Li+-solvent interaction is expected to compatibly improve interfacial charge transport and desolvation kinetics. However, the relationship between physicochemical features and temperature-dependent kinetics properties of SEI remains vague. Herein, we propose four key thermodynamics parameters of SEI potentially influencing low-temperature electrochemistry, including electron work function, Li+ transfer barrier, surface energy, and desolvation energy. Based on the above parameters, we further define a novel descriptor, separation factor of SEI (SSEI), to quantitatively depict charge (Li+/e-) transport and solvent deprivation processes at Gr/electrolyte interface. A Li3PO4-based, inorganics-enriched SEI derived by Li difluorophosphate (LiDFP) additive exhibits the highest SSEI (4.89×103) to enable efficient Li+ conduction, e- blocking and rapid desolvation, and as a result, much suppressed Li-metal precipitation, electrolyte decomposition and Gr sheets exfoliation, thus improving low-temperature battery performances. Overall, our work originally provides visualized guides to improve low-temperature reaction kinetics/thermodynamics by constructing desirable SEI chemistry.

Development of growth selection system and pocket engineering of d-amino acid oxidase to enhance selective deamination activity toward d-phosphinothricin.

D-amino acid oxidase (DAAO)-catalyzed selective oxidative deamination is a very promising process for synthesizing l-amino acids including l-phosphinothricin (l-PPT, a high-efficiency and broad-spectrum herbicide). However, the wild-type DAAO's low activity toward unnatural substrates like d-phosphinothricin (d-PPT) hampers its application. Herein, a DAAO from Caenorhabditis elegans (CeDAAO) was screened and engineered to improve the catalytic potential on d-PPT. First, we designed a novel growth selection system, taking into account the intricate relationship between the growth of Escherichia coli (E. coli) and the catalytic mechanism of DAAO. The developed system was used for high-throughput screening of gene libraries, resulting in the discovery of a variant (M6) with significantly increased catalytic activity against d-PPT. The variant displays different catalytic properties on substrates with varying hydrophobicity and hydrophilicity. Analysis using Alphafold2 modeling and molecular dynamic simulations showed that the reason for the enhanced activity was the substrate-binding pocket with enlarged size and suitable charge distribution. Further QM/MM calculations revealed that the crucial factor for enhancing activity lies in reducing the initial energy barrier of the reductive half reaction. Finally, a comprehensive binding-model index to predict the enhanced activity of DAAO toward d-PPT, and an enzymatic deracemization approach was developed, enabling the efficient synthesis of l-PPT with remarkable efficiency.

In Situ Analysis of Interfacial Morphological and Chemical Evolution in All-Solid-State Lithium-Metal Batteries.

In situ analysis of Li plating/stripping processes and evolution of solid electrolyte interphase (SEI) are critical for optimizing all-solid-state Li metal batteries (ASSLMB). However, the buried solid-solid interfaces present a challenge for detection which preclude the employment of multiple analysis techniques. Herein, by employing complementary in situ characterizations, morphological/chemical evolution, Li plating/stripping dynamics and SEI dynamics were directly detected. As a mixed ionic-electronic conducting interface, Li|Li10GeP2S12 (LGPS) performed distinct interfacial morphological/chemical evolution and dynamics from ionic-conducting/electronic-isolating interface like Li|Li3PS4 (LPS), which were revealed by combination of in situ atomic force microscopy and in situ X-ray photoelectron spectroscopy. Though Li plating speed in LGPS was higher than LPS, speed of SSE decomposition was similar and ~85 % interfacial SSE turned into SEI during plating and remained unchanged in stripping. To leverage strengths of different SSEs, an LPS-LGPS-LPS sandwich electrolyte was developed, demonstrating enhanced ionic conductivity and improved interfacial stability with less SSE decomposition (25 %). Using in situ Kelvin probe force microscopy, Li-ion behavior at interface between different SSEs was effectively visualized, uncovering distribution of Li ions at LGPS|LPS interface under different potentials.

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

A comparative study of microbial changes in dental plaque before and after single- and multiappointment treatments in patients with severe early childhood caries.

BACKGROUND: The status of dental caries is closely related to changes in the oral microbiome. In this study, we compared the diversity and structure of the dental plaque microbiome in children with severe early childhood caries (S-ECC) before and after general anaesthesia and outpatient treatment. METHODS: Forty children aged 3 to 5 years with S-ECC who had completed whole-mouth dental treatment under general anaesthesia (C1) or in outpatient settings (C2) were selected, 20 in each group. The basic information and oral health status of the children were recorded, and the microbial community structure and diversity of dental plaque before treatment (C1, C2), the day after treatment(C2_0D), 7 days after treatment (C1_7D, C2_7D), 1 month after treatment (C1_1M, C2_1M), and 3 months after treatment (C1_3M, C2_3M) were analysed via 16 S rRNA high-throughput sequencing technology. RESULTS: (1) The alpha diversity test showed that the flora richness in the multiappointment group was significantly greater at posttreatment than at pretreatment (P < 0.05), and the remaining alpha diversity index did not significantly differ between the 2 groups (P > 0.05). The beta diversity analysis revealed that the flora structures of the C1_7D group and the C2_3M group were significantly different from those of the other time points within the respective groups (P < 0.05). (2) The core flora existed in both the pre- and posttreatment groups, and the proportion of their flora abundance could be altered depending on the caries status of the children in both groups. Leptotrichia abundance was significantly (P < 0.05) lower at 7 days posttreatment in both the single- and multiappointment groups. Corynebacterium and Corynebacterium_matruchotii were significantly more abundant in the C1_1M and C1_3M groups than in the C1 and C1_7D groups (P < 0.05). Streptococcus, Haemophilus and Haemophilus_parainfluenzae were significantly more abundant in the C1_7D group than in the other groups (P < 0.05). CONCLUSION: A single session of treatment under general anaesthesia can cause dramatic changes in the microbial community structure and composition within 7 days after treatment, whereas treatment over multiple appointments may cause slow changes in oral flora diversity.

Reviving Fatigue Surface for Solid-State Upcycling of Highly Degraded Polycrystalline LiNi1-x-yCoxMnyO2 Cathodes.

The ongoing tide of spent lithium-ion batteries (LIBs) urgently calls for high-value output in efficient recycling. Recently, direct regeneration has emerged as a novel recycling strategy but fails to repair the irreversible morphology and structure damage of the highly degraded polycrystalline layered oxide materials. Here, this work carries out a solid-state upcycling study for the severely cracked LiNi1-x-yCoxMnyO2 cathodes. The specific single-crystallization process during calcination is investigated and the surface rock salt phase is recognized as the intrinsic obstacle to the crystal growth of the degraded cathodes due to sluggish diffusion in the heterogeneous grain boundary. Accordingly, this work revives the fatigue rock salt phase by restoring a layered surface and successfully reshapes severely broken cathodes into the high-performance single-crystalline particles. Benefiting from morphological and structural integrity, the upcycled single-crystalline cathode materials exhibit an enhanced capacity retention rate of 93.5% after 150 cycles at 1C compared with 61.7% of the regenerated polycrystalline materials. The performance is also beyond that of the commercial cathodes even under a high cut-off voltage (4.5 V) or high operating temperature (45 °C). This work provides scientific insights for the upcycling of the highly degraded cathodes in spent LIBs.

Design of NAMPTs with Superior Activity by Dual-Channel Protein Engineering Strategy.

The nicotinamide phosphoribosyltransferase (NAMPT)-catalyzed substitution reaction plays a pivotal role in the biosynthesis of nucleotide compounds. However, industrial applications are hindered by the low activity of NAMPTs. In this study, a novel dual-channel protein engineering strategy was developed to increase NAMPT activity by enhancing substrate accessibility. The best mutant (CpNAMPTY13G+Y15S+F76P) with a remarkable 5-fold increase in enzyme activity was obtained. By utilizing CpNAMPTY13G+Y15S+F76P as a biocatalyst, the accumulation of ß-nicotinamide mononucleotide reached as high as 19.94 g L-1 within 3 h with an impressive substrate conversion rate of 99.8%. Further analysis revealed that the newly generated substrate channel, formed through crack propagation, facilitated substrate binding and enhanced byproduct tolerance. In addition, three NAMPTs from different sources were designed based on the dual-channel protein engineering strategy, and the corresponding dual-channel mutants with improved enzyme activity were obtained, which proved the effectiveness and practicability of the approach.

Smooth muscle NF90 deficiency ameliorates diabetic atherosclerotic calcification in male mice via FBXW7-AGER1-AGEs axis.

Hyperglycemia accelerates calcification of atherosclerotic plaques in diabetic patients, and the accumulation of advanced glycation end products (AGEs) is closely related to the atherosclerotic calcification. Here, we show that hyperglycemia-mediated AGEs markedly increase vascular smooth muscle cells (VSMCs) NF90/110 activation in male diabetic patients with atherosclerotic calcified samples. VSMC-specific NF90/110 knockout in male mice decreases obviously AGEs-induced atherosclerotic calcification, along with the inhibitions of VSMC phenotypic changes to osteoblast-like cells, apoptosis, and matrix vesicle release. Mechanistically, AGEs increase the activity of NF90, which then enhances ubiquitination and degradation of AGE receptor 1 (AGER1) by stabilizing the mRNA of E3 ubiquitin ligase FBXW7, thus causing the accumulation of more AGEs and atherosclerotic calcification. Collectively, our study demonstrates the effects of VSMC NF90 in mediating the metabolic imbalance of AGEs to accelerate diabetic atherosclerotic calcification. Therefore, inhibition of VSMC NF90 may be a potential therapeutic target for diabetic atherosclerotic calcification.