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Abstract Diazo compounds are rare natural products possessing various biological activities. Kinamycin and lomaiviticin, two diazo natural products featured by the diazobenzofluorene core, exhibit exceptional potency as chemotherapeutic agents. Despite the extensive studies on their biosynthetic gene clusters and the assembly of their polyketide scaffolds, the formation of the characteristic diazo group remains elusive. l-Glutamylhydrazine was recently shown to be the hydrazine donor in kinamycin biosynthesis, however, the mechanism for the installation of the hydrazine group onto the kinamycin scaffold is still unclear. Here we describe an O-methyltransferase-like protein, AlpH, which is responsible for the hydrazine incorporation in kinamycin biosynthesis. AlpH catalyses a unique SAM-independent coupling of l-glutamylhydrazine and polyketide intermediate via a rare Mannich reaction in polyketide biosynthesis. Our discovery expands the catalytic diversity of O-methyltransferase-like enzymes and lays a strong foundation for the discovery and development of novel diazo natural products through genome mining and synthetic biology.

During the fault of the wind power collection line of the MMC-HVDC system, the amplitude of the fault current may be limited due to the control of the converter, which leads to the severe limitation of traditional protection. In this paper, based on the difference of negative sequence current accumulation, a new protection scheme for wind farm collection lines is proposed. First, the negative sequence current equivalent circuit of the wind farm collection line is constructed. Then, the distribution characteristics of negative sequence current at different fault locations are identified. On this base, a novel protection scheme based on transient negative sequence current accumulation difference using interconnected blocking signals is proposed. The RTDS simulation results show that the protection scheme can accurately identify faults of different types and locations.

An isolated power grid (IPG) lacks the support of the external power grid, and a single generator or load accounts for a large proportion of the total capacity. Once transient angle instability, the generator and load shedding is not effectively. Phase sequence exchange (PSE) uses power electronic devices to switch the three-phase sequence, thereby reducing the power angle of the generator by 120° and preventing the system from losing stability. This paper proposed a PSE scheme for transient angle instability applied to IPG. The local measurements of IPG are used to identify the critical generator, and the system trajectory is obtained through large-step integration. The stability is assessed by the concavity of the trajectory. Once the trajectory swings from the concave area to the convex area, the IPG loses transient stability, at which point the generators in the critical cluster simultaneously PSE prevent transient instability. Based on Simulink and RTDS platform, the scheme is verified in a 39-bus 10-machine system and an existing IPG system. The results show that the proposed scheme can effectively restore the stability of the IPG, outperforming generators and load shedding.

Deep learning-based template matching in remote sensing has received increasing research attention. Existing anchor box-based and anchor-free methods often suffer from low template localization accuracy in the presence of multimodal, nonrigid deformation and occlusion. To address this problem, we transform the template matching task into a center-point localization task for the first time and propose an end-to-end template matching method based on a novel fully convolutional Siamese network. Furthermore, we propose an adaptive shrinkage cross-correlation scheme, which improves the precision of template localization and alleviates the impact of background clutter without adding any parameters. We also design a scheme that leverages keypoint information to assist in locating the template center, thereby enhancing the precision of template localization. We construct a multimodal template matching dataset to verify the performance of the method in dealing with differences in view, scale, rotation and occlusion in practical application scenarios. Extensive experiments on a public dataset, OTB, the proposed dataset, as well as a remote sensing dataset, SEN1-2, demonstrate that our method achieves state-of-the-art performance.

Background: Resveratrol is a potent phytochemical known for its potential in treating cardiometabolic multimorbidity. However, its underlying mechanisms remain unclear. Our study systematically investigates the effects of resveratrol on cardiometabolic multimorbidity and elucidates its mechanisms using network pharmacology and molecular docking techniques. Methods: We screened cardiometabolic multimorbidity-related targets using the OMIM, GeneCards, and DisGeNET databases, and utilized the DSigDB drug characterization database to predict resveratrol’s effects on cardiometabolic multimorbidity. Target identification for resveratrol was conducted using the TCMSP, SymMap, DrugBank, Swiss Target Prediction, CTD, and UniProt databases. SwissADME and ADMETlab 2.0 simulations were used to predict drug similarity and toxicity profiles of resveratrol. Protein–protein interaction (PPI) networks were constructed using Cytoscape 3.9.1 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed via the DAVID online platform, and target-pathway networks were established. Molecular docking validated interactions between core targets and resveratrol, followed by molecular dynamics simulations on the optimal core proteins identified through docking. Differential analysis using the GEO dataset validated resveratrol as a core target in cardiometabolic multimorbidity. Results: A total of 585 cardiometabolic multimorbidity target genes were identified, and the predicted results indicated that the phytochemical resveratrol could be a major therapeutic agent for cardiometabolic multimorbidity. SwissADME simulations showed that resveratrol has potential drug-like activity with minimal toxicity. Additionally, 6703 targets of resveratrol were screened. GO and KEGG analyses revealed that the main biological processes involved included positive regulation of cell proliferation, positive regulation of gene expression, and response to estradiol. Significant pathways related to MAPK and PI3K-Akt signaling pathways were also identified. Molecular docking and molecular dynamics simulations demonstrated strong interactions between resveratrol and core targets such as MAPK and EGFR. Conclusions: This study predicts potential targets and pathways of resveratrol in treating cardiometabolic multimorbidity, offering a new research direction for understanding its molecular mechanisms. Additionally, it establishes a theoretical foundation for the clinical application of resveratrol.

Utilizing unmanned aerial vehicles (UAVs) as mobile access points or base stations has emerged as a promising solution to address the excessive traffic demands in wireless networks. This paper investigates improving the detector performance at the unmanned aerial vehicle base stations (UAV-BSs) in an uplink grant-free non-orthogonal multiple access (GF-NOMA) system by considering the activity state (AS) temporal correlation of the different user equipments (UEs) in the time domain. The Bernoulli Gaussian-Markov chain (BG-MC) probability model is used for exploiting both the sparsity and slow change characteristic of the AS of the UE. The GAMP Bernoulli Gaussian-Markov chain (GAMP-BG-MC) algorithm is proposed to improve the detector performance, which can utilize the bidirectional message passing between the neighboring time slots to fully exploit the temporally correlated AS of the UE. Furthermore, the parameters of the BG-MC model can be updated adaptively during the estimation procedure with unknown system statistics. Simulation results show that the proposed algorithm can improve the detection accuracy compared to existing methods while keeping the same order complexity.

Nasopharyngeal carcinoma (NPC) requires regular follow-up to detect recurrence as early as possible. However, many patients are unable to regularly follow up due to the inconvenience of the conventional approach. Therefore, this study was designed to investigate the impact of the online clinic on follow-up compliance and prognosis in NPC patients. Patients who were first diagnosed with NPC between April 2019 and November 2019 were enrolled. Good follow-up compliance was defined as having at least one follow-up visit every 6 months within 2 years after treatment completion. Sensitivity analyses were performed using a propensity score matching model. A total of 539 (42%) patients used online follow-up while 731 (58%) used traditional follow-up. The median age of patients in the online cohort was lower than that in the traditional cohort (44 vs. 47, p < 0.001). Compared with the traditional cohort, the online cohort had significantly better follow-up compliance (57.3% vs. 17.1%, p < 0.001) and a higher 2-year PFS rate (98.1% vs. 94.4%, p = 0.003). Survival analysis showed that online follow-up was an independent factor for better survival prognosis (HR 0.39, 95%CI 0.20–0.74, p = 0.004). Sensitivity analysis further confirmed these results. Our study found that the online clinic increased follow-up compliance and improved prognosis in NPC patients.

The metabolic network’s primary sources of free fatty acids (FFAs) are long- and medium-chain fatty acids of triglyceride origin and short-chain fatty acids produced by intestinal microorganisms through dietary fibre fermentation. Recent studies have demonstrated that FFAs not only serve as an energy source for the body’s metabolism but also participate in regulating arterial function. Excess FFAs have been shown to lead to endothelial dysfunction, vascular hypertrophy, and vessel wall stiffness, which are important triggers of arterial hypertension and atherosclerosis. Nevertheless, free fatty acid receptors (FFARs) are involved in the regulation of arterial functions, including the proliferation, differentiation, migration, apoptosis, inflammation, and angiogenesis of vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). They actively regulate hypertension, endothelial dysfunction, and atherosclerosis. The objective of this review is to examine the roles and heterogeneity of FFAs and FFARs in the regulation of arterial function, with a view to identifying the points of intersection between their actions and providing new insights into the prevention and treatment of diseases associated with arterial dysfunction, as well as the development of targeted drugs.

Persimmon (Diospyros kaki Thunb.) fruit size variation is abundant. Studying the size of the persimmon fruit is helpful in improving its economic value. At present, the regulatory mechanism of persimmon fruit size formation is still unclear. In this study, the mechanism of fruit size formation was investigated through morphological, cytological and transcriptomic analyses, as well as exogenous ethrel and aminoethoxyinylglycine (AVG: ethylene inhibitor) experiments using the large fruit and small fruit of ‘Yaoxianwuhua’. The results showed that stages 3–4 (June 11–June 25) are the crucial morphological period for differentiation of large fruit and small fruit in persimmon. At this crucial morphological period, the cell number in large fruit was significantly more than that in small fruit, indicating that the difference in cell number is the main reason for the differentiation of persimmon fruit size. The difference in cell number was caused by cell division. CNR1, ANT, LAC17 and EB1C, associated with cell division, may be involved in regulating persimmon fruit size. Exogenous ethrel resulted in a decrease in fruit weight, and AVG treatment had the opposite effect. In addition, LAC17 and ERF114 were upregulated after ethrel treatment. These results indicated that high ethylene levels can reduce persimmon fruit size, possibly by inhibiting cell division. This study provides valuable information for understanding the regulation mechanism of persimmon fruit size and lays a foundation for subsequent breeding and artificial regulation of fruit size.

Ficus is a significant genus within the Moraceae family, primarily native to tropical and subtropical regions. It plays a crucial role in the study of co-evolution and genetics in the fig–fig wasp symbiosis. Advancements in sequencing technology have facilitated whole-genome sequencing of several Ficus species, accumulating vast amounts of genomic and transcriptomic data available in public databases. To streamline data integration, display, and analysis, we developed the Ficus Genome Database (FGD), a consolidated platform for the genomic data of five Ficus species, and self-assembled transcriptome data for 24 fig ostiolar bracts. The FGD is currently home to a diverse array of data, encompassing genome and gene sequences, annotations of genes, transcriptome analyses, biochemical pathways, non-coding RNA, and findings from comparative genomic studies, such as collinear blocks across different Ficus genome assemblies. To enhance translational and practical research concerning Ficus, FGD provides an extensive suite of accessible query interfaces, analytical instruments, and visualization options. These include the NCBI BLAST sequence search tool and the JBrowse/GBrowse genome browser. FGD also offers several distinct tools, including a genome Synteny Viewer, expression heatmap display, gene family identification, Gene Ontology terms enrichment, and pathway enrichment analysis.

The selective separation of small molecules at the sub-nanometer scale has broad application prospects in the field, such as energy, catalysis, and separation. Conventional polymeric membrane materials (e.g., nanofiltration membranes) for sub-nanometer scale separations face challenges, such as inhomogeneous channel sizes and unstable pore structures. Combining polymers with metal–organic frameworks (MOFs), which possess uniform and intrinsic pore structures, may overcome this limitation. This combination has resulted in three distinct types of membranes: MOF polycrystalline membranes, mixed-matrix membranes (MMMs), and thin-film nanocomposite (TFN) membranes. However, their effectiveness is hindered by the limited regulation of the surface properties and growth of MOFs and their poor interfacial compatibility. The main issues in preparing MOF polycrystalline membranes are the uncontrollable growth of MOFs and the poor adhesion between MOFs and the substrate. Here, polymers could serve as a simple and precise tool for regulating the growth and surface functionalities of MOFs while enhancing their adhesion to the substrate. For MOF mixed-matrix membranes, the primary challenge is the poor interfacial compatibility between polymers and MOFs. Strategies for the mutual modification of MOFs and polymers to enhance their interfacial compatibility are introduced. For TFN membranes, the challenges include the difficulty in controlling the growth of the polymer selective layer and the performance limitations caused by the “trade-off” effect. MOFs can modulate the formation process of the polymer selective layer and establish transport channels within the polymer matrix to overcome the “trade-off” effect limitations. This review focuses on the mechanisms of synergistic construction of polymer–MOF membranes and their structure–nanofiltration performance relationships, which have not been sufficiently addressed in the past.

PurposeSteroid-induced osteonecrosis of the femoral head (SONFH) is a refractory orthopedic hip joint disease that primarily affects middle-aged and young individuals. SONFH may be caused by ischemia and hypoxia of the femoral head, where mitochondria play a crucial role in oxidative reactions. Currently, there is limited literature on whether mitochondria are involved in the progression of SONFH. Here, we aim to identify and validate key potential mitochondrial-related genes in SONFH through bioinformatics analysis. This study aims to provide initial evidence that mitochondria play a role in the progression of SONFH and further elucidate the mechanisms of mitochondria in SONFH.MethodsThe GSE123568 mRNA expression profile dataset includes 10 non-SONFH (non-steroid-induced osteonecrosis of the femoral head) samples and 30 SONFH samples. The GSE74089 mRNA expression profile dataset includes 4 healthy samples and 4 samples with ischemic necrosis of the femoral head. Both datasets were downloaded from the Gene Expression Omnibus (GEO) database. The mitochondrial-related genes are derived from MitoCarta3.0, which includes data for all 1136 human genes with high confidence in mitochondrial localization based on integrated proteomics, computational, and microscopy approaches. By intersecting the GSE123568 and GSE74089 datasets with a set of mitochondrial-related genes, we screened for mitochondrial-related genes involved in SONFH. Subsequently, we used the good Samples Genes method in R language to remove outlier genes and samples in the GSE123568 dataset. We further used WGCNA to construct a scale-free co-expression network and selected the hub gene set with the highest connectivity. We then intersected this gene set with the previously identified mitochondrial-related genes to select the genes with the highest correlation. A total of 7 mitochondrial-related genes were selected. Next, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the selected mitochondrial-related genes using R software. Furthermore, we performed protein network analysis on the differentially expressed proteins encoded by the mitochondrial genes using STRING. We used the GSEA software to group the genes within the gene set in the GSE123568 dataset based on their coordinated changes and evaluate their impact on phenotype changes. Subsequently, we grouped the samples based on the 7 selected mitochondrial-related genes using R software and observed the differences in immune cell infiltration between the groups. Finally, we evaluated the prognostic significance of these features in the two datasets, consisting of a total of 48 samples, by integrating disease status and the 7 gene features using the cox method in the survival R package. We performed ROC analysis using the roc function in the pROC package and evaluated the AUC and confidence intervals using the ci function to obtain the final AUC results.ResultsIdentification and analysis of 7 intersecting DEGs (differentially expressed genes) were obtained among peripheral blood, cartilage samples, hub genes, and mitochondrial-related genes. These 7 DEGs include FTH1, LACTB, PDK3, RAB5IF, SOD2, and SQOR, all of which are upregulated genes with no intersection in the downregulated gene set. Subsequently, GO and KEGG pathway enrichment analysis revealed that the upregulated DEGs are primarily involved in processes such as oxidative stress, release of cytochrome C from mitochondria, negative regulation of intrinsic apoptotic signaling pathway, cell apoptosis, mitochondrial metabolism, p53 signaling pathway, and NK cell-mediated cytotoxicity. GSEA also revealed enriched pathways associated with hub genes. Finally, the diagnostic value of these key genes for hormone-related ischemic necrosis of the femoral head (SONFH) was confirmed using ROC curves.ConclusionBID, FTH1, LACTB, PDK3, RAB5IF, SOD2, and SQOR may serve as potential diagnostic mitochondrial-related biomarkers for SONFH. Additionally, they hold research value in investigating the involvement of mitochondria in the pathogenesis of ischemic necrosis of the femoral head.

Background: The prognostic significance of the ratio of activated CD4 T cells to Tregs infiltrating tumor tissues in gastric cancer (GC) remains unknown. Materials and methods: For the quantification of infiltration of immune cells, the ssGSEA algorithm, which is a single sample gene set enrichment analysis, was utilized. Group A was defined as having activated CD4 T cells/Tregs >1, while group B was defined as having activated CD4 T cells/Tregs

AimDental erosion is a chemical-mechanical process that leads to the loss of dental hard tissues. This study aimed to investigate the effect of pomegranate juice on the enamel.MethodsEnamel blocks were randomly divided into three groups: deionized water, cola, and pomegranate juice. The blocks were immersed in the solutions four times a day for 14 days, and stored in artificial saliva for the remaining period. The surface hardness was measured on days 7 and 14. The surface structures of the demineralized blocks were observed via scanning electron microscopy (SEM), and the depth of demineralization was observed via confocal laser scanning microscopy (CLSM). The pH, calcium, and phosphorus levels of the three solutions were analyzed.ResultsThe microhardness values of the blocks in the pomegranate juice and cola groups decreased with the increase in the demineralization time. The blocks in the pomegranate juice group exhibited large fractures in the enamel column, whereas those in the cola group had pitted enamels with destruction of the interstitial enamel column. Compared with cola group, fluorescent penetration increased in pomegranate juice (P < 0.01). The pH of cola (2.32 ± 0.09) was lower than that of pomegranate juice (3.16 ± 0.16). Furthermore, the calcium content in pomegranate juice was significantly higher than that in cola (P < 0.01). Alternatively, the concentration of phosphorous in cola was significantly higher than that in pomegranate juice (P < 0.01).ConclusionThese findings indicate that pomegranate juice can cause enamel demineralization with an erosive potential comparable to that of cola.

Abstract Background Previous studies have shown that high level of TILs in invasive lobular carcinoma (ILC) is associated with poor prognosis, contrary to that in TNBC and HER2‐positive breast cancer. Methods The densities of six immune cell markers and three immune checkpoints in the ILC microenvironment were detected by computational pathology analysis. Then, the LASSO cox regression model was used to construct an immune score (IS) and further evaluate its prognostic value. Results In our ILC cohort, the low density of CD4, CD8, CD20, CD56, CD68, FOXP3, PD‐1, and PD‐L1 had significantly longer disease‐free survival (DFS) and overall survival (OS); however, the low density of CTLA‐4 was associated with shorter DFS and OS. Based on this, an IS was constructed, and patients with low‐IS had significantly prolonged DFS (p

PurposeTo explore the association between type 2 diabetes mellitus (T2DM) and body composition based on magnetic resonance fat fraction (FF) mapping.MethodsA total of 341 subjects, who underwent abdominal MRI examination with FF mapping were enrolled in this study, including 68 T2DM patients and 273 non-T2DM patients. The FFs and areas of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and abdominal muscle (AM) were measured at the level of the L1-L2 vertebral. The FF of bone marrow adipose tissue (BMAT) was determined by the averaged FF values measured at the level of T12 and L1 vertebral, respectively. The whole hepatic fat fraction (HFF) and pancreatic fat fraction (PFF) were measured based on 3D semi-automatic segmentation on the FF mapping. All data were analyzed by GraphPad Prism and MedCalc.ResultsVAT area, VAT FF, HFF, PFF of T2DM group were higher than those of non-T2DM group after adjusting for age and sex (P < 0.05). However, there was no differences in SAT area, SAT FF, BMAT FF, AM area and AM FF between the two groups (P > 0.05). VAT area and PFF were independent risk factors of T2DM (all P < 0.05). The area under the curve (AUC) of the receiver operating characteristic (ROC) for VAT area and PFF in differentiating between T2DM and non-T2DM were 0.685 and 0.787, respectively, and the AUC of PFF was higher than VAT area (P < 0.05). Additionally, in seemingly healthy individuals, the SAT area, VAT area, and AM area were found to be significantly associated with being overweight and/or obese (BMI ≥ 25) (all P < 0.05).ConclusionsIn this study, it was found that there were significant associations between T2DM and VAT area, VAT FF, HFF and PFF. In addition, VAT area and PFF were the independent risk factors of T2DM. Especially, PFF showed a high diagnostic performance in discrimination between T2DM and non-T2DM. These findings may highlight the crucial role of PFF in the pathophysiology of T2DM, and it might be served as a potential imaging biomarker of the prevention and treatment of T2DM. Additionally, in individuals without diabetes, focusing on SAT area, VAT area and AM area may help identify potential health risks and provide a basis for targeted weight management and prevention measures.

Premenstrual syndrome (PMS) occurs recurrently during the luteal phase of a woman’s menstrual cycle and disappears after menstruation ends. It is characterized by abnormal changes in both the body and mood, and in certain cases, severe disruptions in daily life and even suicidal tendencies. Current drugs for treating PMS, such as selective serotonin reuptake inhibitors, do not yield satisfactory results. Orexin, a neuropeptide produced in the lateral hypothalamus, is garnering attention in the treatment of neurological disorders and is believed to modulate the symptoms of PMS. This paper reviews the advancements in research on sleep disturbances, mood changes, and cognitive impairment caused by PMS, and suggests potential pathways for orexin to address these symptoms. Furthermore, it delves into the role of orexin in the molecular mechanisms underlying PMS. Orexin regulates steroid hormones, and the cyclic fluctuations of estrogen and progesterone play a crucial role in the pathogenesis of PMS. Additionally, orexin also modulates the gamma-aminobutyric acid (GABA) system and the inflammatory response involved in coordinating the mechanism of PMS. Unraveling the role of orexin in the pathogenesis of PMS will not only aid in understanding the etiology of PMS but also hold implications for orexin as a novel target for treating PMS.

Objective: In this paper, we present a comprehensive overview of our experience in establishing and leading distinct extracorporeal cardiopulmonary resuscitation (ECPR)-related teams to independently handle ECPR in the early stages in the emergency department. Methods: A retrospective analysis was conducted on the clinical data of 29 patients who underwent ECPR treatment in the emergency room between May 2018 and April 2022. A control group, consisting of 10 patients treated between May 2018 and September 2019 was managed using a standard rescue coordination mode. The 19 patients who received ECPR between October 2019 and April 2022 were treated by members of the department's 24-h extracorporeal life support team. We compared the implementation and operational challenges faced by the two groups, including item preparation, circuit setup, and ECPR initiation times, among other factors. Results: Gender, age, cardiac arrest risk factors, and other baseline data did not significantly differ between the two groups. Extracorporeal membrane oxygenation (ECMO) pipeline prefilling time (from 35.27±10.34 to 13.46±5.32), ECPR establishment time (from 62.35±29.61 to 30.98±13.41), and item preparation time (from 16.42±9.78 to 3.19±1.49) all considerably decreased when compared to the control group. The rate of return of spontaneous circulation recovery rose from 37.50 % to 77.78 % (P

This study focuses on a novel clutchless and synchronizer-free drive system designed explicitly for pure electric vehicles. In contrast to the majority of previous research that solely considers internal excitations, this study not only incorporates various non-linear factors such as time-varying friction forces, time-varying mesh stiffness, and damping associated with internal excitations but also places significant emphasis on analyzing the impact of non-linear external excitations, including road surface unevenness and motor torque fluctuations, on the shifting process of the drive system. Subsequently, a non-linear dynamic model of the shifting process is established. In the modeling process, departing from the traditional two-degree-of-freedom quarter vehicle dynamics model, this study adopts an elastic tire-body and elastic tire-tread tire model, enabling the establishment of a highly accurate multi-degree-of-freedom quarter vehicle dynamics model. The simulation results indicate that road surface roughness and motor torque fluctuation significantly impact the gear-shifting process and the impact of road surface roughness increases with the level of roughness. Moreover, the effect of motor torque fluctuation on the gear-shifting process varies depending on different factors and is not simply additive. Consequently, when formulating and optimizing shifting strategies, it becomes imperative to consider various external factors. The research methodology integrates these factors into the dynamic analysis of the shifting process, providing a theoretical basis for developing effective shifting control strategies while considering external excitations.

Abstract The electrochemical–mechanical degradation of ultrahigh Ni cathode for lithium‐ion batteries is a crucial aspect that limits the cycle life and safety of devices. Herein, the study reports a facile strategy involving rational design of primary grain crystallographic orientation within polycrystalline cathode, which well enhanced its electro‐mechanical strength and Li+ transfer kinetics. Ex situ and in situ experiments/simulations including cross‐sectional particle electron backscatter diffraction (EBSD), single‐particle micro‐compression, thermogravimetric analysis combined with mass spectrometry (TGA‐MS), and finite element modeling reveal that, the primary‐grain‐alignment strategy effectively mitigates the particle pulverization, lattice oxygen release thereby enhances battery cycle life and safety. Besides the preexisting doping and coating methodologies to improve the stability of Ni‐rich cathode, the primary‐grain‐alignment strategy, with no foreign elements or heterophase layers, is unprecedently proposed here. The results shed new light on the study of electrochemical–mechanical strain alleviation for electrode materials.

ABSTRACTBrucellosis, caused by Brucella, is a severe zoonosis, and the current Brucella live attenuated vaccine cannot be used in humans due to major safety risks. Although polysaccharide antigens can be used to prepare the Brucella vaccine, their lower immunogenicity limits them from producing efficient and broad protection. In this study, we produced a high-performance bioconjugate nanovaccine against different species of Brucella by introducing a self-assembly nanoparticle platform and an O-linked glycosylation system into Yersinia enterocolitica serotype O:9, which has an O-polysaccharide composed of the same unit as Brucella. After successfully preparing the vaccine and confirming its stability, we subsequently demonstrated the safety of the vaccine in mice by high-dose immunization. Then, by a series of mouse experiments, we found that the nanovaccine greatly promoted antibody responses. In particular, the increase of IgG2a was more obvious than that of IgG1. Most importantly, this nanovaccine could provide cross-protection against B. abortus, B. melitensis, and B. suis strains by lethal dose challenged models, and could improve the clearance of B. melitensis, the most common pathogenic species in human brucellosis, by non-lethal dose infection. Overall, for the first time, we biocoupled polysaccharide antigens with nano carriers to prepare a Brucella vaccine, which showed pronounced and extensive protective effects in mice. Thus, we provided a potential candidate vaccine and a new direction for Brucella vaccine design.