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Objectives: The objective of this study was to analyse the global, regional, and national burdens of ischaemic heart disease (IHD) in adults aged 15-49 years and its attributable risk factors from 1990 to 2019., Study Design: Epidemiological study., Methods: Data were obtained from the Global Burden of Disease (GBD) Study 2019. The estimated annual percentage change was used to evaluate temporal trends in incidence, deaths, and disability-adjusted life years (DALYs) of youth IHD. We selected IHD-associated risk factors, including five environmental/occupational factors, 16 behavioural risks, and five metabolic factors. We computed the age-standardised rates and percentage of age-standardised DALY rates attributable to these factors of youth IHD., Results: Globally, there were 2.26 million cases of incidence, 0.63 million deaths, and 30.58 million DALYs in 2019. The age-standardised incidence, death, and DALY rates decreased from 1990 to 2019, whereas the absolute number of incidences, deaths, and DALYs increased significantly. Globally, approximately 94.1% of age-standardised DALY rates from IHD in youths aged 15-49 years are attributable to risk factors listed in the GBD 2019 dataset. The leading global and regional risk factors for youth IHD in 2019 were high low-density lipoprotein cholesterol (68.9%), high systolic blood pressure (51.2%), high body mass index (33.1%), smoking (30.5%), and ambient particulate-matter pollution (25.4%)., Conclusions: The burden of IHD among young people is still heavy, and metabolic risk factors are the leading drivers of IHD. Therefore, formulating relevant policies to control and treat cardiovascular risk factors is an effective measure to reduce the IHD burden in youth., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

The air traffic information network is fundamental for ensuring the efficient and safe operation of flights. However, with the increasing demands of air traffic services, the rigidity of the traditional air traffic information network has become increasingly pronounced. Network function virtualization (NFV) technology presents an effective solution to address this issue. Within the NFV environment, the deployment of service function chains (SFC) forms the basis for achieving end-to-end air traffic services. This paper addresses the low delay and high security requirements inherent in air traffic services and proposes an efficient and secure SFC deployment for delay optimization (ESSFCD-DO) method. Primarily, the paper conducts a theoretical analysis of SFC deployment, and derives four key principles related to SFC delay, security, and resource cost. Subsequently, based on these principles, the ESSFCD-DO method is developed, which encompasses the virtual network function (VNF) aggregation algorithm for security and resources cost optimization (VNFAA-SRCO), the VNF deployment algorithm based on topology aware (VNFD-TA), and the algorithm for deploying virtual links based on k-shortest path. Experimental results demonstrate that, in comparison to other SFC deployment methods within this domain, ESSFCD-DO achieves significant optimizations in terms of end-to-end delay of SFC and long-term revenue-cost ratio, while ensuring security and service request acceptance rate., (© 2024. The Author(s).)

Targeted immunotherapies make substantial strides in clinical cancer care due to their ability to counteract the tumor's capacity to suppress immune responses. Advances in biomimetic technology with minimally immunogenic and highly targeted, are addressing issues of targeted drug delivery and disrupting the tumor's immunosuppressive environment to trigger immune activation. Specifically, the use of dendritic cell (DC) membranes to coat nanoparticles ensures targeted delivery due to DC's unique ability to activate naive T cells, spotlighting their role in immunotherapy aimed at disrupting the tumor microenvironment. The potential of DC's biomimetic membrane to mediate immune activation and target tumors is gaining momentum, enhancing the effectiveness of cancer treatments in conjunction with other immune responses. This review delves into the methodologies behind crafting DC membranes and the fusion of dendritic and tumor cell membranes for encapsulating therapeutic nanoparticles. It explores their applications and recent advancements in combating cancer, offering an all-encompassing perspective on DC biomimetic nanosystems, immunotherapy driven by antigen presentation, and the collaborative efforts of drug delivery in chemotherapy and photodynamic therapies. Current evidence shows promise in augmenting combined therapeutic approaches for cancer treatment and holds translational potential for various cancer treatments in a clinical setting., (© 2024. The Author(s).)

Super enhancers (SEs) are large clusters of transcriptional enhancers driving the expression of genes crucial for defining cell identity. In cancer, tumor-specific SEs activate key oncogenes, leading to tumorigenesis. Identifying SE-driven oncogenes in tumors and understanding their functional mechanisms is of significant importance. In this study, a previously unreported SE region is identified in T-cell acute lymphoblastic leukemia (T-ALL) patient samples and cell lines. This SE activates the expression of interferon regulatory factor 2 binding protein 2 (IRF2BP2) and is regulated by T-ALL master transcription factors (TFs) such as ETS transcription factor ERG (ERG), E74 like ETS transcription factor 1 (ELF1), and ETS proto-oncogene 1, transcription factor (ETS1). Hematopoietic system-specific IRF2BP2 conditional knockout mice is generated and showed that IRF2BP2 has minimal impact on normal T cell development. However, in vitro and in vivo experiments demonstrated that IRF2BP2 is crucial for T-ALL cell growth and survival. Loss of IRF2BP2 affects the MYC and E2F pathways in T-ALL cells. Cleavage under targets and tagmentation (CUT&Tag) assays and immunoprecipitation revealed that IRF2BP2 cooperates with the master TFs of T-ALL cells, targeting the enhancer of the T-ALL susceptibility gene recombination activating 1 (RAG1) and modulating its expression. These findings provide new insights into the regulatory network within T-ALL cells, identifying potential new targets for therapeutic intervention., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

LncRNAs are involved in modulating the individual risk and the severity of progression in metabolic dysfunction-associated fatty liver disease (MASLD), but their precise roles remain largely unknown. This study aimed to investigate the role of lncRNA Snhg3 in the development and progression of MASLD, along with the underlying mechanisms. The result showed that Snhg3 was significantly downregulated in the liver of high-fat diet-induced obesity (DIO) mice. Notably, palmitic acid promoted the expression of Snhg3 and overexpression of Snhg3 increased lipid accumulation in primary hepatocytes. Furthermore, hepatocyte-specific Snhg3 deficiency decreased body and liver weight, alleviated hepatic steatosis and promoted hepatic fatty acid metabolism in DIO mice, whereas overexpression induced the opposite effect. Mechanistically, Snhg3 promoted the expression, stability and nuclear localization of SND1 protein via interacting with SND1, thereby inducing K63-linked ubiquitination modification of SND1. Moreover, Snhg3 decreased the H3K27me3 level and induced SND1-mediated chromatin loose remodeling, thus reducing H3K27me3 enrichment at the Pparg promoter and enhancing PPARγ expression. The administration of PPARγ antagonist T0070907 improved Snhg3 -aggravated hepatic steatosis. Our study revealed a new signaling pathway, Snhg3 /SND1/H3K27me3/PPARγ, responsible for mice MASLD and indicates that lncRNA-mediated epigenetic modification has a crucial role in the pathology of MASLD., Competing Interests: XX, MG, WZ, CL, WZ, JY, YZ, EC, YG, ZG, MZ, EN, HW, XW, YZ, YW, XL, HY, LY, FF, ML, AQ, XL No competing interests declared, (© 2024, Xie et al.)

Maternal anemia has been identified as a contributing factor to adverse reproductive outcomes associated with cadmium (Cd) exposure, a common heavy metal. Our recent findings suggest that inhibited erythroid differentiation and enucleation also play significant roles in the direct embryonic toxicity resulting from maternal Cd exposure. However, the effects of Cd exposure on lipid metabolism remodeling, which is essential for physiological erythropoiesis, remain poorly understood. In the present study, pregnant mice were administered low doses of CdCl 2 via oral exposure from early to late gestation to mitigate Cd-induced maternal anemia. Compared to vehicle-treated controls, embryos from Cd-treated mice exhibited a slight decrease in weight, though without signs of atrophy. Consistent with our previous observations, fetal livers from Cd-exposed embryos demonstrated a dose-dependent inhibition of erythroid differentiation, as confirmed by ex vivo analysis. Notably, an intrinsic decrease in lipid peroxidation during erythroid differentiation was observed in the bone marrow and fetal livers of vehicle-treated mice, attributed to diminished lipid content. In contrast, this decrease in lipid peroxidation was absent in fetal liver erythroblasts from Cd-treated mice, where an increase in lipid peroxidation was instead noted. These findings elucidate a potential mechanism, lipid peroxidation, underlying Cd-induced embryonic toxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Parkinson's disease is characterized by multiple neurotransmitter systems beyond the traditional dopaminergic pathway, yet their influence on volumetric alterations is not well comprehended. We included 72 de novo, drug-naïve Parkinson's disease patients and 61 healthy controls. Voxel-wise gray matter volume was evaluated between Parkinson's disease and healthy controls, as well as among Parkinson's disease subgroups categorized by clinical manifestations. The Juspace toolbox was utilized to explore the spatial relationship between gray matter atrophy and neurotransmitter distribution. Parkinson's disease patients exhibited widespread GM atrophy in the cerebral and cerebellar regions, with spatial correlations with various neurotransmitter receptors (FDR-P < 0.05). Cognitively impaired Parkinson's disease patients showed gray matter atrophy in the left middle temporal atrophy, which is associated with serotoninergic, dopaminergic, cholinergic, and glutamatergic receptors (FDR-P < 0.05). Postural and gait disorder patients showed atrophy in the right precuneus, which is correlated with serotoninergic, dopaminergic, gamma-aminobutyric acid, and opioid receptors (FDR-P < 0.05). Patients with anxiety showed atrophy in the right superior orbital frontal region; those with depression showed atrophy in the left lingual and right inferior occipital regions. Both conditions were linked to serotoninergic and dopaminergic receptors (FDR-P < 0.05). Parkinson's disease patients exhibited regional gray matter atrophy with a significant distribution of specific neurotransmitters, which might provide insights into the underlying pathophysiology of clinical manifestations and develop targeted intervention strategies., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Super-enhancers (SEs) typically govern the expression of critical oncogenes and play a fundamental role in the initiation and progression of cancer. Focusing on genes that are abnormally regulated by SE in cancer may be a new strategy for understanding pathogenesis. In the context of this investigation, we have identified a previously unreported SE-driven gene IRF2BP2 in neuroblastoma (NB)., Methods: The expression and prognostic value of IRF2BP2 were detected in public databases and clinical samples. The effect of IRF2BP2 on NB cell growth and apoptosis was evaluated through in vivo and in vitro functional loss experiments. The molecular mechanism of IRF2BP2 was investigated by the study of chromatin regulatory regions and transcriptome sequencing., Results: The sustained high expression of IRF2BP2 results from the activation of a novel SE established by NB master transcription factors MYCN, MEIS2, and HAND2, and they form a new complex that regulates the gene network associated with the proliferation of NB cell populations. We also observed a significant enrichment of the AP-1 family at the binding sites of IRF2BP2. Remarkably, within NB cells, AP-1 plays a pivotal role in shaping the chromatin accessibility landscape, thereby exposing the binding site for IRF2BP2. This orchestrated action enables AP-1 and IRF2BP2 to collaboratively stimulate the expression of the NB susceptibility gene ALK, thereby upholding the highly proliferative phenotype characteristic of NB., Conclusions: Our findings indicate that SE-driven IRF2BP2 can bind to AP-1 to maintain the survival of tumor cells via regulating chromatin accessibility of the NB susceptibility gene ALK., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Lymph-node status is important in decision-making during early gastric cancer (EGC) treatment. Currently, endoscopic submucosal dissection is the mainstream treatment for EGC. However, it is challenging for even experienced endoscopists to accurately diagnose and treat EGC. Multiphoton microscopy can extract the morphological features of collagen fibers from tissues. The characteristics of collagen fibers can be used to assess the lymph-node metastasis status in patients with EGC. First, we compared the accuracy of four deep learning models (VGG16, ResNet34, MobileNetV2, and PVTv2) in training preprocessed images and test datasets. Next, we integrated the features of the best-performing model, which was PVTv2, with manual and clinical features to develop a novel model called AutoLNMNet. The prediction accuracy of AutoLNMNet for the no metastasis (Ly0) and metastasis in lymph nodes (Ly1) stages reached 0.92, which was 0.3% higher than that of PVTv2. The receiver operating characteristics of AutoLNMNet in quantifying Ly0 and Ly1 stages were 0.97 and 0.97, respectively. Therefore, AutoLNMNet is highly reliable and accurate in detecting lymph-node metastasis, providing an important tool for the early diagnosis and treatment of EGC., (© 2024 Wiley Periodicals LLC.)

Background: Platycodon grandiflorum (P. grandiflorum) is a commonly used medicinal plant in China. Transcriptome sequencing studies of different tissues of P. grandiflorum have been widely conducted. However, studies on transcriptome sequencing and expression patterns of key genes in the saponin synthesis pathway of Tongcheng P. grandiflorum, a high-quality medicinal resource of different years, are relatively limited., Results: This study involved transcriptome sequencing and bioinformatics analysis of the roots from annual, biennial, and triennial P. grandiflorum in the Tongcheng area. After data filtering and assembly, we obtained 111.44 Gb of clean base data, including 742,880616 clean reads. We identified 5,156 differential expression unigenes between at least two sample groups, with differences noted among annual, biennial, and triennial P. grandiflorum plants. GO enrichment analysis annotated 3509, 1819, and 1393 DEGs in comparison TC1vsTC2, TC1vsTC3, and TC2vsTC3, respectively. Furthermore, KEGG enrichment analysis identified 16 genes encoding key enzymes in the terpene skeleton biosynthesis, sesquiterpene and triterpene biosynthesis pathways, including SE, AACT, FPPS, DXR, HMGR, HMGS, and DXS. The results of qRT-PCR experiments showed that most of the genes were most highly expressed in annual P. grandiflorum., Conclusions: The present study provided transcriptomic data from the roots of Tongcheng P. grandiflorum of different years, which provides critical bioinformatics data on the growth and development of P. grandiflorum, laying a foundation for further research on saponins and identifying key enzymes involved in this process across different growth stages., (© 2024. The Author(s).)

The genetic transcription profile and underlying molecular mechanisms of ischemic stroke (IS) remain elusive. To address this issue, four mRNA and one miRNA expression profile of rats with middle cerebral artery occlusion (MCAO) were acquired from the Gene Expression Omnibus (GEO) database. A total of 780 differentially expressed genes (DEGs) and 56 miRNAs (DEMs) were screened. Gene set and functional enrichment analysis revealed that a substantial number of immune-inflammation-related pathways were abnormally activated in IS. Through weighted gene co-expression network analysis, the turquoise module was identified as meaningful. By taking the intersection of the turquoise module genes, DEM-target genes, and all DEGs, 354 genes were subsequently obtained as key IS-related genes. Among them, six characteristic genes were identified using the least absolute shrinkage and selection operator. After validation with three external datasets, transforming growth factor beta 1 (Tgfb1) was selected as the hub gene. This finding was further confirmed by gene expression pattern analysis in both the MCAO model rats and clinical IS patients. Moreover, the expression of the hub genes exhibited a negative correlation with the modified Rankin scale score (P < 0.05). Collectively, these results expand our knowledge of the genetic profile and molecular mechanisms involved in IS and suggest that the Tgfb1 gene is a potential biomarker of this disease., (© 2024. The Author(s).)

Purpose: This meta-analysis was conducted to assess the relative diagnostic effectiveness of [ 18 F]FDG PET/CT and MRI in the initial detection of ovarian cancer., Methods: A thorough literature search was conducted using PubMed, Embase, and Web of Science databases to locate relevant studies published up to April 2024. The selected studies were those that evaluated diagnostic performance of [ 18 F]FDG PET/CT and MRI for the initial detection of ovarian cancer. Sensitivity and specificity metrics were analyzed employing the DerSimonian and Laird random-effects model, with further transformation utilizing the Freeman-Tukey double arcsine method. The quality of included studies was appraised using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool., Results: The meta-analysis included 23 articles encompassing a total of 1973 patients. The sensitivity of [ 18 F]FDG PET/CT was found to be higher than that of MRI (0.94 vs. 0.87, P = 0.02). In terms of specificity, [ 18 F]FDG PET/CT and MRI demonstrated similar values (0.87 vs. 0.86, P = 0.90). An assessment of publication bias using the funnel plot asymmetry test revealed no significant bias for any outcomes (Egger's test: all P > 0.05)., Conclusions: Our meta-analysis reveals that [ 18 F]FDG PET/CT exhibits higher sensitivity while maintaining similar specificity compared to MRI for the initial detection of ovarian cancer. However, the substantial heterogeneity observed across studies may influence these findings. Consequently, larger-scale prospective studies are necessary to validate these results., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Recent studies have highlighted type 2 diabetes (T2DM) as a significant risk factor for the development of metabolic dysfunction-associated fatty liver disease (MAFLD). This investigation aimed to assess electroacupuncture's (EA) impact on liver morphology and function in T2DM rats, furnishing experimental substantiation for its potential to stall MAFLD progression in T2DM., Methods: T2DM rats were induced by a high-fat diet and a single intraperitoneal injection of streptozotocin, and then randomly assigned to five groups: the T2DM group, the electroacupuncture group, the metformin group, combination group of electroacupuncture and metformin, combination group of electroacupuncture and Compound C. The control group received a standard diet alongside intraperitoneal citric acid - sodium citrate solution injections. After a 6-week intervention, the effects of each group on fasting blood glucose, lipids, liver function, morphology, lipid droplet infiltration, and fibrosis were evaluated. Techniques including Western blotting, qPCR, immunohistochemistry, and immunofluorescence were employed to gauge the expression of key molecules in AMPK-associated glycolipid metabolism, insulin signaling, autophagy, and fibrosis pathways. Additionally, transmission electron microscopy facilitated the observation of liver autophagy, lipid droplets, and fibrosis., Results: Our studies indicated that hyperglycemia, hyperlipidemia and IR promoted lipid accumulation, pathological and functional damage, and resulting in hepatic steatosis and fibrosis. Meanwhile, EA enhanced the activation of AMPK, which in turn improved glycolipid metabolism and autophagy through promoting the expression of PPARα/CPT1A and AMPK/mTOR pathway, inhibiting the expression of SREBP1c, PGC-1α/PCK2 and TGFβ1/Smad2/3 signaling pathway, ultimately exerting its effect on ameliorating hepatic steatosis and fibrosis in T2DM rats. The above effects of EA were consistent with metformin. The combination of EA and metformin had significant advantages in increasing hepatic AMPK expression, improving liver morphology, lipid droplet infiltration, fibrosis, and reducing serum ALT levels. In addition, the ameliorating effects of EA on the progression of MAFLD in T2DM rats were partly disrupted by Compound C, an inhibitor of AMPK., Conclusions: EA upregulated hepatic AMPK expression, curtailing gluconeogenesis and lipogenesis while boosting fatty acid oxidation and autophagy levels. Consequently, it mitigated blood glucose, lipids, and insulin resistance in T2DM rats, thus impeding liver steatosis and fibrosis progression and retarding MAFLD advancement., (© 2024. The Author(s).)

Assessment of tissue microenvironment lactate levels has emerged as a crucial indicator of microcirculation and early organ dysfunction. Lactylation modification, closely associated with lactate concentration, represents a novel post-translational alteration targeting protein lysine residues. Post-translational modifications are chemical changes capable of modulating protein activity and functionality, serving as a rapid mechanism for enhancing proteomic diversity and influencing various life processes. While previous research primarily focused on histone lactylation, recent studies have revealed the occurrence of lactylation on non-histone proteins, exerting significant effects on gene expression and intercellular communication. Lactylation has been implicated in diverse diseases spanning embryonic development, neuronal excitability, inflammatory responses, cardiovascular conditions, tumor progression, invasion, and aging. Hence, lactylation emerges as a pivotal regulator in numerous pathological conditions. This review delves into the mechanisms underlying lactylation and disease pathogenesis, elucidates the multifaceted roles of lactylation in disease progression, and identifies novel therapeutic targets related to lactylation, offering potential avenues for future clinical interventions.

Omniphobic membranes, due to their exceptional properties, have drawn significant attention for overcoming the bottleneck in membrane distillation (MD) technology. This study demonstrates an innovative method for fabricating an omniphobic membrane that is simple and facile compared to other methods such as wet/dry etching and photolithography. The surface morphology of springtails was imitated using electrospraying technique to coat a polyvinylidene fluoride substrate with concave-shaped polystyrene beads that were successfully developed by controlling the electrical traction (voltage) and air resistance (humidity). Then, the lipid coating of springtail surfaces was mimicked by dip-coating the membrane in a low-toxicity short-chain perfluoropolyether lubricant. The concave structure's tiny air pockets increased membrane hydrophobicity significantly, indicated by the fact that the first round of water bouncing took only 16.3 ms. Finally, in MD treatment of seawater containing 1.0 mM sodium dodecyl sulfate, the optimized omniphobic membrane maintained a stable 99.9% salt rejection rate., (© 2024. The Author(s).)

Background: Recurrent Clostridioides difficile infection (CDI) is a critical clinical issue due to the increase in incidence and difficulty in treatment. We aimed to identify gut microbial and metabolic features associated with disease recurrence in a group of pediatric CDI patients., Methods: A total of 84 children with primary CDI were prospectively enrolled in the study. Fecal samples collected at the initial diagnosis were subjected to 16S rRNA gene sequencing and targeted metabolomics analysis to profile the bacterial composition and metabolome., Results: Twenty-six of 84 (31.0%) pediatric CDI patients experienced recurrence. The alpha diversity of the fecal microbiota was significantly lower in the recurrent group than in the nonrecurrent group, and the beta diversity was different from that of the nonrecurrent group. Taxonomic profiles revealed that the relative abundances of multiple bacterial taxa significantly differed between the recurrent and nonrecurrent groups. Linear discriminant analysis effect size analysis identified several bacterial genera that discriminated between recurrent and nonrecurrent groups, including Parabacteroides , Coprococcus , Dialister , and Clostridium . Recurrent bacteria presented lower abundances of several short-chain fatty acid (SCFA)-producing bacteria ( Faecalibacterium , Butyricicoccus , Clostridium , Roseburia , and Ruminococcus ), which were correlated with reduced fecal SCFA levels. In addition, several bile acids, including lithocholic acid (LCA), 12-ketoLCA, trihydroxycholestanoic acid, and deoxycholic acid, were decreased in recurrent patients., Conclusions: Our study suggests that the differing gut microbiota profiles in pediatric CDI patients may contribute to disease recurrence by modulating SCFA concentrations and bile acid profiles. The gut microbiota and metabolite signatures may be used to predict disease recurrence in children with CDI., Competing Interests: Potential conflicts of interest. All authors: No potential conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The cross-regulation of immunity and metabolism is currently a research hotspot in life sciences and immunology. Metabolic immunology plays an important role in cutting-edge fields such as metabolic regulatory mechanisms in immune cell development and function, and metabolic targets and immune-related disease pathways. Protein post-translational modification (PTM) is a key epigenetic mechanism that regulates various biological processes and highlights metabolite functions. Currently, more than 400 PTM types have been identified to affect the functions of several proteins. Among these, metabolic PTMs, particularly various newly identified histone or non-histone acylation modifications, can effectively regulate various functions, processes and diseases of the immune system, as well as immune-related diseases. Thus, drugs aimed at targeted acylation modification can have substantial therapeutic potential in regulating immunity, indicating a new direction for further clinical translational research. This review summarises the characteristics and functions of seven novel lysine acylation modifications, including succinylation, S-palmitoylation, lactylation, crotonylation, 2-hydroxyisobutyrylation, β-hydroxybutyrylation and malonylation, and their association with immunity, thereby providing valuable references for the diagnosis and treatment of immune disorders associated with new acylation modifications., (© 2024 John Wiley & Sons Ltd.)

Objective: Our objective was to explore the patterns of resting-state network (RSN) connectivity alterations and investigate how the influences of individual-level network connections on cognition varied across clinical stages without assuming a constant relationship., Methods: 108 PD patients with continuum of cognitive decline (PD-NC = 46, PD-MCI = 43, PDD = 19) and 34 healthy controls (HCs) underwent resting-state functional MRI and neuropsychological tests. Independent component analysis (ICA) and graph theory analyses (GTA) were employed to explore RSN connection changes. Additionally, stage-dependent differential impact of network communication on cognitive performance were examined using sparse varying coefficient modeling., Results: Compared to HCs, the dorsal attention network (DAN) and dorsal sensorimotor network (dSMN) were central networks with decreased connections in PD-NC and PD-MCI stage, while the lateral visual network (LVN) emerged as a central network in patients with dementia. Additionally, connectivity of the cerebellum network (CBN) increased in the PD-NC and PD-MCI stages. GTA demonstrated decreased nodal metrics for DAN and dSMN, coupled with an increase for CBN. Moreover, the degree centrality (DC) values of DAN and dSMN exhibited a stage-dependent differential impact on cognitive performance across the continuum of cognitive decline., Conclusion: Our findings suggest that across the progression of cognitive impairment, the LVN gradually transitions into a core node with reduced connectivity, while the enhancement of connections in CBN diminishes. Furthermore, the non-linear relationship between the DC values of RSNs and cognitive decline indicates the potential for tailored interventions targeting specific stages., Competing Interests: Declaration of competing interest The authors declare no potential conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Ovarian cancer is among the most common gynecological cancers and the eighth leading cause of cancer-related deaths among women worldwide. Surgery is among the most important options for cancer treatment. During surgery, a biopsy is generally required to screen for lesions; however, traditional case examinations are time consuming and laborious and require extensive experience and knowledge from pathologists. Therefore, this study proposes a simple, fast, and label-free ovarian cancer diagnosis method that combines second harmonic generation (SHG) imaging and deep learning. Unstained fresh human ovarian tissues were subjected to SHG imaging and accurately characterized using the Pyramid Vision Transformer V2 (PVTv2) model. The results showed that the SHG imaged collagen fibers could quantify ovarian cancer. In addition, the PVTv2 model could accurately differentiate the 3240 SHG images obtained from our imaging collection into benign, normal, and malignant images, with a final accuracy of 98.4%. These results demonstrate the great potential of SHG imaging techniques combined with deep learning models for diagnosing the diseased ovarian tissues., (© 2024 Wiley‐VCH GmbH.)

Objective: Aortic dissection (AD) is a prevalent and acute clinical catastrophe characterized by abrupt manifestation, swift progression, and elevated fatality rates. Despite smoking being a significant risk factor for AD, the precise pathological process remains elusive. This investigation endeavors to explore the mechanisms by which smoking accelerates AD through ferroptosis induction., Methodology: In this novel study, we detected considerable endothelial cell death by ferroptosis within the aortic inner lining of both human AD patients with a smoking history and murine AD models induced by β-aminopropionitrile, angiotensin II, and nicotine. Utilizing bioinformatic approaches, we identified microRNAs regulating the expression of the ferroptosis inhibitor Glutathione peroxidase 4 (GPX4). Nicotine's impact on ferroptosis was further assessed in human umbilical vein endothelial cells (HUVECs) through modulation of miR-1909-5p. Additionally, the therapeutic potential of miR-1909-5p antagomir was evaluated in vivo in nicotine-exposed AD mice., Findings: Our results indicate a predominance of ferroptosis over apoptosis, pyroptosis, and necroptosis in the aortas of AD patients who smoke. Nicotine exposure instigated ferroptosis in HUVECs, where the miR-1909-5p/GPX4 axis was implicated. Modulation of miR-1909-5p in these cells revealed its regulatory role over GPX4 levels and subsequent endothelial ferroptosis. In vivo, miR-1909-5p suppression reduced ferroptosis and mitigated AD progression in the murine model., Conclusions: Our data underscore the involvement of the miR-1909-5p/GPX4 axis in the pathogenesis of nicotine-induced endothelial ferroptosis in AD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

JOURNAL/nrgr/04.03/01300535-202412000-00028/figure1/v/2024-04-08T165401Z/r/image-tiff Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal cord injury. They can greatly affect nerve regeneration and functional recovery. However, there is still limited understanding of the peripheral immune inflammatory response in spinal cord injury. In this study, we obtained microRNA expression profiles from the peripheral blood of patients with spinal cord injury using high-throughput sequencing. We also obtained the mRNA expression profile of spinal cord injury patients from the Gene Expression Omnibus (GEO) database (GSE151371). We identified 54 differentially expressed microRNAs and 1656 differentially expressed genes using bioinformatics approaches. Functional enrichment analysis revealed that various common immune and inflammation-related signaling pathways, such as neutrophil extracellular trap formation pathway, T cell receptor signaling pathway, and nuclear factor-κB signal pathway, were abnormally activated or inhibited in spinal cord injury patient samples. We applied an integrated strategy that combines weighted gene co-expression network analysis, LASSO logistic regression, and SVM-RFE algorithm and identified three biomarkers associated with spinal cord injury: ANO10, BST1, and ZFP36L2. We verified the expression levels and diagnostic performance of these three genes in the original training dataset and clinical samples through the receiver operating characteristic curve. Quantitative polymerase chain reaction results showed that ANO10 and BST1 mRNA levels were increased and ZFP36L2 mRNA was decreased in the peripheral blood of spinal cord injury patients. We also constructed a small RNA-mRNA interaction network using Cytoscape. Additionally, we evaluated the proportion of 22 types of immune cells in the peripheral blood of spinal cord injury patients using the CIBERSORT tool. The proportions of naïve B cells, plasma cells, monocytes, and neutrophils were increased while the proportions of memory B cells, CD8+ T cells, resting natural killer cells, resting dendritic cells, and eosinophils were markedly decreased in spinal cord injury patients increased compared with healthy subjects, and ANO10, BST1 and ZFP26L2 were closely related to the proportion of certain immune cell types. The findings from this study provide new directions for the development of treatment strategies related to immune inflammation in spinal cord injury and suggest that ANO10, BST1, and ZFP36L2 are potential biomarkers for spinal cord injury. The study was registered in the Chinese Clinical Trial Registry (registration No. ChiCTR2200066985, December 12, 2022)., (Copyright © 2024 Copyright: © 2024 Neural Regeneration Research.)

Background: Infantile Juvenile polyposis of infantile (JPI) is a rare and aggressive form of juvenile polyposis syndrome (JPS) typically diagnosed in the first year of life. It often carries a poor prognosis due to chronic gastrointestinal bleeding, protein-losing enteropathy, malnutrition and immune deficiency., Case Presentation: We report a case of a girl initially presented with pallor at 7 months of age, which progressed to gastrointestinal bleeding and protein-losing enteropathy. Endoscopic examination, which included both upper gastrointestinal endoscopy and enteroscopy, showed diffuse polyposis. Histopathology results indicated the presence of juvenile polyps with no dysplasia in all removed polyps. Genetic testing identified a 2.1 Mb deletion on chromosome 10q23.2q23.31 involving the phosphatase and tensin homolog (PTEN) and bone morphogenetic protein receptor type IA (BMPR1A) genes. Treatment with sirolimus initiated at 10 months of age led to a reduction in the need for blood and albumin infusions, improved patient growth, and quality of life. While the frequency of endoscopic evaluations decreased with sirolimus, regular endoscopic polypectomy every 5 months remained necessary. However, discontinuation of sirolimus resulted in polyp recurrence after 2 months due to pneumonia., Conclusion: This case highlights sirolimus treatment can alleviate many complications of JPI, it does not eliminate the need for aggressive polypectomy., (© 2024. The Author(s).)

Long noncoding RNAs (lncRNAs) are strongly associated with glucose homeostasis, but their roles remain largely unknown. In this study, the potential role of lncRNA-Snhg3 in glucose metabolism was evaluated both in vitro and in vivo. Here, we found a positive relationship between Snhg3 and hepatic glycogenesis. Glucose tolerance improved in hepatocyte-specific Snhg3 knock-in (Snhg3-HKI) mice, while it worsened in hepatocyte-specific Snhg3 knockout (Snhg3-HKO) mice. Furthermore, hepatic glycogenesis had shown remarkable increase in Snhg3-HKI mice and reduction in Snhg3-HKO mice, respectively. Mechanistically, Snhg3 increased mRNA and protein expression levels of PPP1R3B through inducing chromatin remodeling and promoting the phosphorylation of protein kinase B. Collectively, these results suggested that lncRNA-Snhg3 plays a critical role in hepatic glycogenesis., (© 2024 Federation of American Societies for Experimental Biology.)

Simple and scalable production of micro-supercapacitors (MSCs) is crucial to address the energy requirements of miniature electronics. Although significant advancements have been achieved in fabricating MSCs through solution-based printing techniques, the realization of high-performance MSCs remains a challenge. In this paper, graphene-based MSCs with a high power density were prepared through screen printing of aqueous conductive inks with appropriate rheological properties. High electrical conductivity (2.04 × 10 4 S∙m -1 ) and low equivalent series resistance (46.7 Ω) benefiting from the dense conductive network consisting of the mesoporous structure formed by graphene with carbon black dispersed as linkers, as well as the narrow finger width and interspace (200 µm) originating from the excellent printability, prompted the fully printed MSCs to deliver high capacitance (9.15 mF∙cm -2 ), energy density (1.30 µWh∙cm -2 ) and ultrahigh power density (89.9 mW∙cm -2 ). Notably, the resulting MSCs can effectively operate at scan rates up to 200 V∙s -1 , which surpasses conventional supercapacitors by two orders of magnitude. In addition, the MSCs demonstrate excellent cycling stability (91.6% capacity retention and ~100% Coulombic efficiency after 10,000 cycles) and extraordinary mechanical properties (92.2% capacity retention after 5000 bending cycles), indicating their broad application prospects in flexible wearable/portable electronic systems.

Helminths serve as principal regulators in modulating host immune responses, and their excretory-secretory proteins are recognized as potential therapeutic agents for inflammatory bowel disease. Nevertheless, our comprehension of the mechanisms underlying immunoregulation remains restricted. This investigation delves into the immunomodulatory role of a secretory protein serpin ( Emu -serpin), within the larval stage of Echinococcus multilocularis . Our observations indicate that Emu -serpin effectively alleviates dextran sulfate sodium-induced colitis, yielding a substantial reduction in immunopathology and an augmentation of anti-inflammatory cytokines. Furthermore, this suppressive regulatory effect is concomitant with the reduction of gut microbiota dysbiosis linked to colitis, as evidenced by a marked impediment to the expansion of the pathobiont taxa Enterobacteriaceae. In vivo experiments demonstrate that Emu -serpin facilitates the expansion of M2 phenotype macrophages while concurrently diminishing M1 phenotype macrophages, alongside an elevation in anti-inflammatory cytokine levels. Subsequent in vitro investigations involving RAW264.7 and bone marrow macrophages reveal that Emu -serpin induces a conversion of M2 macrophage populations from a pro-inflammatory to an anti-inflammatory phenotype through direct inhibition. Adoptive transfer experiments reveal the peritoneal macrophages induced by Emu -serpin alleviate colitis and gut microbiota dysbiosis. In summary, these findings propose that Emu -serpin holds the potential to regulate macrophage polarization and maintain gut microbiota homeostasis in colitis, establishing it as a promising candidate for developing helminth therapy for preventing inflammatory diseases., Competing Interests: The authors declare no conflict of interest.

Background: Although brain glymphatic dysfunction is a contributing factor to the cognitive deficits in Parkinson's disease (PD), its role in the longitudinal progression of cognitive dysfunction remains unknown., Objective: To investigate the glymphatic function in PD with mild cognitive impairment (MCI) that progresses to dementia (PDD) and to determine its predictive value in identifying individuals at high risk for developing dementia., Methods: We included 64 patients with PD meeting criteria for MCI and categorized them as either progressed to PDD (converters) (n = 29) or did not progress to PDD (nonconverters) (n = 35), depending on whether they developed dementia during follow-up. Meanwhile, 35 age- and gender-matched healthy controls (HC) were included. Bilateral diffusion-tensor imaging analysis along the perivascular space (DTI-ALPS) indices and enlarged perivascular spaces (EPVS) volume fraction in bilateral centrum semiovale, basal ganglia (BG), and midbrain were compared among the three groups. Correlations among the DTI-ALPS index and EPVS, as well as cognitive performance were analyzed. Additionally, we investigated the mediation effect of EPVS on DTI-ALPS and cognitive function., Results: PDD converters had lower cognitive composites scores in the executive domains than did nonconverters (P < 0.001). Besides, PDD converters had a significantly lower DTI-ALPS index in the left hemisphere (P < 0.001) and a larger volume fraction of BG-PVS (P = 0.03) compared to HC and PDD nonconverters. Lower DTI-ALPS index and increased BG-PVS volume fraction were associated with worse performance in the global cognitive performance and executive function. However, there was no significant mediating effect. Receiver operating characteristic analysis revealed that the DTI-ALPS could effectively identify PDD converters with an area under the curve (AUC) of 0.850., Conclusion: The reduction of glymphatic activity, measured by the DTI-ALPS, could potentially be used as a non-invasive indicator in forecasting high risk of dementia conversion before the onset of dementia in PD patients., (© 2024. The Author(s).)

Aortic dissection (AD) is a severe cardiovascular disease necessitating active therapeutic strategies for early intervention and prevention. Nucleic acid drugs, known for their potent molecule-targeting therapeutic properties, offer potential for genetic suppression of AD. Piwi-interacting RNAs, a class of small RNAs, hold promise for managing cardiovascular diseases. Limited research on these RNAs and AD exists. This study demonstrates that an antagomir targeting heart-apoptosis-associated piRNA (HAAPIR) effectively regulates vascular remodeling, mitigating AD occurrence and progression through the myocyte enhancer factor 2D (Mef2D) and matrix metallopeptidase 9 (MMP9) pathways. Green tea-derived plant exosome-like nanovesicles (PELNs) are used for oral administration of antagomir. The antagomir-HAAPIR-nanovesicle complex, after purification and optimization, exhibits a high packing rate, while the antagomir is resistant to enzyme digestion. Administered to mice, the complex targets the aortic lesion, reducing AD incidence and improving survival. Moreover, MMP9 and Mef2D expression decrease significantly, inhibiting the phenotypic conversion of human aortic smooth muscle cells. PELNs encapsulate the antagomir-HAAPIR complex, maintaining stability, mediating transport into the bloodstream, and delivering Piwi-interacting RNAs to AD sites. Thus, HAAPIR is a potential target for persistent clinical AD prevention and treatment, and nanovesicle-encapsulated nucleic acids offer a promising cardiovascular disease treatment, providing insights for other therapeutic targets., (© 2024 Wiley‐VCH GmbH.)

Background: Osteosarcoma (OS) is one of the most common primary malignant tumors of bone in children, which develops from osteoblasts and typically occurs during the rapid growth phase of the bone. Recently, Super-Enhancers(SEs)have been reported to play a crucial role in osteosarcoma growth and metastasis. Therefore, there is an urgent need to identify specific targeted inhibitors of SEs to assist clinical therapy. This study aimed to elucidate the role of BRD4 inhibitor GNE-987 targeting SEs in OS and preliminarily explore its mechanism., Methods: We evaluated changes in osteosarcoma cells following treatment with a BRD4 inhibitor GNE-987. We assessed the anti-tumor effect of GNE-987 in vitro and in vivo by Western blot, CCK8, flow cytometry detection, clone formation, xenograft tumor size measurements, and Ki67 immunohistochemical staining, and combined ChIP-seq with RNA-seq techniques to find its anti-tumor mechanism., Results: In this study, we found that extremely low concentrations of GNE-987(2-10 nM) significantly reduced the proliferation and survival of OS cells by degrading BRD4. In addition, we found that GNE-987 markedly induced cell cycle arrest and apoptosis in OS cells. Further study indicated that VHL was critical for GNE-987 to exert its antitumor effect in OS cells. Consistent with in vitro results, GNE-987 administration significantly reduced tumor size in xenograft models with minimal toxicity, and partially degraded the BRD4 protein. KRT80 was identified through analysis of the RNA-seq and ChIP-seq data. U2OS HiC analysis suggested a higher frequency of chromatin interactions near the KRT80 binding site. The enrichment of H3K27ac modification at KRT80 was significantly reduced after GNE-987 treatment. KRT80 was identified as playing an important role in OS occurrence and development., Conclusions: This research revealed that GNE-987 selectively degraded BRD4 and disrupted the transcriptional regulation of oncogenes in OS. GNE-987 has the potential to affect KRT80 against OS., (© 2024. The Author(s).)

With the increasing urban environmental problems, spontaneous vegetation has been gradually emphasized for high ecological value, whose distribution has been reported as strongly influenced by fine-scale environmental factors. As one of the major zones for urban spontaneous vegetation distribution, urban riparian corridors are well suited for research on the response of spontaneous plants to microhabitats. Taking the Wenyu River-North Canal in Beijing as the study site, we measured six microhabitat factors, including the level of maintenance and visitor activity, canopy density, litter thickness, and distance to water and road, to investigate their effects on spontaneous plant assemblages. The results showed that spontaneous plants respond significantly to fine-scale habitat variation, and were more responsive to human disturbance than other factors. Compared with diversity indicators, the functional trait compositions were more significantly correlated with microhabitat factors. Under lower maintenance of plants, the spontaneous communities had a higher invasion risk for plants. Thick litter can impede the occurrence of invasive species while favoring the growth of native ones. Our findings are important for furthering understanding of the spontaneous plant community establishment, and can serve as a good reference for the maintenance and management of spontaneous plants in urban riparian corridors., (© 2024. The Author(s).)

Background: Despite the use of targeted therapeutic approaches, T-cell acute lymphoblastic leukemia (T-ALL) is still associated with a high incidence of complications and a poor prognosis. Indisulam (also known as E7070), a newly identified molecular glue compound, has demonstrated increased therapeutic efficacy in several types of cancer through the rapid degradation of RBM39. This study aimed to evaluate the therapeutic potential of indisulam in T-ALL, elucidate its underlying mechanisms and explore the role of the RBM39 gene., Methods: We verified the anticancer effects of indisulam in both in vivo and in vitro models. Additionally, the construction of RBM39-knockdown cell lines using shRNA confirmed that the malignant phenotype of T-ALL cells was dependent on RBM39. Through RNA sequencing, we identified indisulam-induced splicing anomalies, and proteomic analysis helped pinpoint protein changes caused by the drug. Comprehensive cross-analysis of these findings facilitated the identification of downstream effectors and subsequent validation of their functional roles., Results: Indisulam has significant antineoplastic effects on T-ALL. It attenuates cell proliferation, promotes apoptosis and interferes with cell cycle progression in vitro while facilitating tumor remission in T-ALL in vivo models. This investigation provides evidence that the downregulation of RBM39 results in the restricted proliferation of T-ALL cells both in vitro and in vivo, suggesting that RBM39 is a potential target for T-ALL treatment. Indisulam's efficacy is attributed to its ability to induce RBM39 degradation, causing widespread aberrant splicing and abnormal translation of the critical downstream effector protein, THOC1, ultimately leading to protein depletion. Moreover, the presence of DCAF15 is regarded as critical for the effectiveness of indisulam, and its absence negates the ability of indisulam to induce the desired functional alterations., Conclusion: Our study revealed that indisulam, which targets RBM39 to induce tumor cell apoptosis, is an effective drug for treating T-ALL. Targeting RBM39 through indisulam leads to mis-splicing of pre-mRNAs, resulting in the loss of key effectors such as THOC1., (© 2024. The Author(s).)

Tin dioxide is regarded as an alternative anode material rather than graphite due to its high theoretical specific capacity. Modification with carbon is a typical strategy to mitigate the volume expansion effect of SnO 2 during the charge process. Strengthening the interface bonding is crucial for improving the electrochemical performance of SnO 2 /C composites. Here, SnO 2 -embedded reduced graphene oxide (rGO) composite with a low graphene content of approximately 5 wt.% was in situ synthesized via a cetyltrimethylammonium bromide (CTAB)-assisted hydrothermal method. The structural integrity of the SnO 2 /rGO composite is significantly improved by optimizing the Sn-O-C electronic structure with CTAB, resulting a reversible capacity of 598 mAh g -1 after 200 cycles at a current density of 1 A g -1 . CTAB-assisted synthesis enhances the rate performance and cyclic stability of tin dioxide/graphene composites, and boosts their application as the anode materials for the next-generation lithium-ion batteries., (© 2024. The Author(s).)

Previous research on the consequences of ethical voice has largely focused on the performance or social relational consequences of ethical voice on multiple organizational stakeholders. The present research provides an important extension to the ethical voice literature by investigating the distinct intrapersonal and interpersonal moral self-regulatory processes that shape ethical voicers' own psychological experiences and their subsequent purposeful efforts to maintain a positive sense of moral self. On one hand, we argue that ethical voice heightens voicers' sense of responsibility over ethical matters at work (i.e., moral ownership), which motivates them to refrain from violating moral norms (i.e., disengaging from unethical behaviors). On the contrary, we argue that ethical voice generates psychological pressure for voicers as they become anxious about preserving their moral social image (i.e., moral reputation maintenance concerns), which motivates them to signal their moral character to others through symbolic acts (i.e., engaging in moral symbolization behaviors). Further, we expect gender differences in the moral consequences of ethical voice. Across two studies that varied in temporal focus (a multisource, time-lagged field study and a within-person weekly experience sampling study), we found support for most of our predictions. The results suggest that while potentially psychologically uplifting (for both men and women), ethical voice also generates psychological pressure for the voicer to preserve their favorable moral social image and thus motivates them (more so in the case of women voicers at the between-person level) to explicitly symbolize their moral character in the workplace. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Sympathetic hyperinnervation is the leading cause of fatal ventricular arrhythmia (VA) after myocardial infarction (MI). Cardiac mast cells cause arrhythmias directly through degranulation. However, the role and mechanism of mast cell degranulation in sympathetic remodeling remain unknown. We investigated the role of oxytocin (OT) in stabilizing cardiac mast cells and improving sympathetic innervation in rats. MI was induced by coronary artery ligation. Western blotting, immunofluorescence, and toluidine staining of mast cells were performed to determine the expression and location of target protein. Mast cells accumulated significantly in peri-infarcted tissues and were present in a degranulated state. They expressed OT receptor (OTR), and OT infusion reduced the number of degranulated cardiac mast cells post-MI. Sympathetic hyperinnervation was attenuated as assessed by immunofluorescence for tyrosine hydroxylase (TH). Seven days post-MI, the arrhythmia score of programmed electrical stimulation was higher in vehicle-treated rats with MI than in rats treated with OT. An in vitro study showed that OT stabilized mast cells via the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Further in vivo studies on OTR-deficient mice showed worsening mast cell degranulation and worsening sympathetic innervation. OT pretreatment inhibited cardiac mast cell degranulation post-MI and prevented sympathetic hyperinnervation, along with mast cell stabilization via the PI3K/Akt pathway. SIGNIFICANCE STATEMENT: This is the first study to elucidate the role and mechanism of oxytocin (OT) in inflammatory-sympathetic communication mediated sympathetic hyperinnervation after myocardial infarction (MI), providing new approaches to prevent fatal arrhythmias., (Copyright © 2024 by The Author(s).)

Nitrogen removal is essential for restoring eutrophic lakes. Microorganisms and aquatic plants in lakes are both crucial for removing excess nitrogen. However, microplastic (MP) pollution and the invasion of exotic aquatic plants have become increasingly serious in lake ecosystems due to human activity and plant-dominant traits. This field mesocosm study explored how the diversity of invasive submerged macrophytes affects denitrification (DNF), anammox (ANA), and dissimilatory nitrate reduction to ammonium (DNRA) in lake sediments with varying MPs. Results showed that invasive macrophytes suppressed DNF rates, but DNRA and ANA were less sensitive than DNF to the diversity of invasive species. Sediment MPs increased the biomass of invasive species more than native species, but did not affect microbial processes. The effects of MPs on nitrate dissimilatory reduction were process-specific. MPs increased DNF rates and the competitive advantage of DNF over DNRA by changing the sediment environment. The decoupling of DNF and ANA was also observed, with increased DNF rates and decreased ANA rates. The study findings suggested new insights into how the invasion of exotic submerged macrophytes affects the sediment nitrogen cycle complex environments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rationale and Objectives: Although both Multiple system atrophy (MSA) and Parkinson's disease (PD) belong to alpha-synucleinopathy, they have divergent clinical courses and prognoses. The degeneration of white matter has a considerable impact on cognitive performance, yet it is uncertain how PD and MSA affect its functioning in a similar or different manner., Methods: In this study, a total of 116 individuals (37 PD with mild cognitive impairment (PD-MCI), 37 MSA (parkinsonian variant) with mild cognitive impairment (MSA-MCI), and 42 healthy controls) underwent diffusion tensor imaging (DTI) and cognitive assessment. Utilizing probabilistic fiber tracking, association fibers, projection fibers, and thalamic fibers were reconstructed. Subsequently, regression, support vector machine, and SHAP (Shapley Addictive exPlanations) analyzes were conducted to evaluate the association between microstructural diffusion metrics and multiple cognitive domains, thus determining the white matter predictors of MCI., Results: MSA-MCI patients exhibited distinct white matter impairment extending to the middle cerebellar peduncle, corticospinal tract, and cingulum bundle. Furthermore, the fractional anisotropy (FA) and mean diffusivity (MD)values of the right anterior thalamic radiation were significantly associated with global efficiency (FA: B = 0.69, P < 0.001, VIF = 1.31; MD: B = -0.53, P = 0.02, VIF = 2.50). The diffusion metrics of white matter between PD-MCI and MSA-MCI proved to be an effective predictor of the MCI, with an accuracy of 0.73 (P < 0.01), and the most predictive factor being the MD of the anterior thalamic radiation., Conclusions: Our results demonstrated that MSA-MCI had a more noticeable deterioration in white matter, which potentially linked to various cognitive domain connections. Diffusion MRI could be a useful tool in comprehending the neurological basis of cognitive impairment in Parkinsonian disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of Interest The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. The manuscript has not been published in any other journal., (Copyright © 2024. Published by Elsevier Inc.)

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy originating from T progenitor cells. It accounts for 15% of childhood and 25% of adult ALL cases. GNE-987 is a novel chimeric molecule developed using proteolysis-targeting chimeras (PROTAC) technology for targeted therapy. It consists of a potent inhibitor of the bromodomain and extraterminal (BET) protein, as well as the E3 ubiquitin ligase Von Hippel-Lindau (VHL), which enables the effective induction of proteasomal degradation of BRD4. Although GNE-987 has shown persistent inhibition of cell proliferation and apoptosis, its specific antitumor activity in T-ALL remains unclear. In this study, we aimed to investigate the molecular mechanisms underlying the antitumor effect of GNE-987 in T-ALL. To achieve this, we employed technologies including RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq) and CUT&Tag. The degradation of BET proteins, specifically BRD4, by GNE-987 has a profound impact on T-ALL cell. In in vivo experiments, sh-BRD4 lentivirus reduced T-ALL cell proliferation and invasion, extending the survival time of mice. The RNA-seq and CUT&Tag analyses provided further insights into the mechanism of action of GNE-987 in T-ALL. These analyses revealed that GNE-987 possesses the ability to suppress the expression of various genes associated with super-enhancers (SEs), including lymphoblastic leukemia 1 (LCK). By targeting these SE-associated genes, GNE-987 effectively inhibits the progression of T-ALL. Importantly, SE-related oncogenes like LCK were identified as critical targets of GNE-987. Based on these findings, GNE-987 holds promise as a potential novel candidate drug for the treatment of T-ALL., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Freezing of gait (FOG), a specific survival-threatening gait impairment, needs to be urgently explored in patients with multiple system atrophy (MSA), which is characterized by rapid progression and death within 10 years of symptom onset. The objective of this study was to explore the topological organisation of both low- and high-order functional networks in patients with MAS and FOG., Method: Low-order functional connectivity (LOFC) and high-order functional connectivity FC (HOFC) networks were calculated and further analysed using the graph theory approach in 24 patients with MSA without FOG, 20 patients with FOG, and 25 healthy controls. The relationship between brain activity and the severity of freezing symptoms was investigated in patients with FOG., Results: Regarding global topological properties, patients with FOG exhibited alterations in the whole-brain network, dorsal attention network (DAN), frontoparietal network (FPN), and default network (DMN), compared with patients without FOG. At the node level, patients with FOG showed decreased nodal centralities in sensorimotor network (SMN), DAN, ventral attention network (VAN), FPN, limbic regions, hippocampal network and basal ganglia network (BG), and increased nodal centralities in the FPN, DMN, visual network (VIN) and, cerebellar network. The nodal centralities of the right inferior frontal sulcus, left lateral amygdala and left nucleus accumbens (NAC) were negatively correlated with the FOG severity., Conclusion: This study identified a disrupted topology of functional interactions at both low and high levels with extensive alterations in topological properties in MSA patients with FOG, especially those associated with damage to the FPN. These findings offer new insights into the dysfunctional mechanisms of complex networks and suggest potential neuroimaging biomarkers for FOG in patients with MSA., Competing Interests: Declaration of competing interest The authors declare no potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: High-altitude pulmonary edema (HAPE) is a severe and potentially fatal condition with limited treatment options. Although ceramide kinase (CERK)-derived ceramide-1-phosphate (C1P) has been demonstrated to offer protection against various pulmonary diseases, its effects on HAPE remain unclear., Objectives: Our study aimed to investigate the potential role of CERK-derived C1P in the development of HAPE and to reveal the molecular mechanisms underlying its protective effects. We hypothesized that CERK-derived C1P could protect against HAPE by stabilizing circadian rhythms and maintaining mitochondrial dynamics., Methods: To test our hypothesis, we used CERK-knockout mice and established HAPE mouse models using a FLYDWC50-1C hypobaric hypoxic cabin. We utilized a range of methods, including lipidomics, transcriptomics, immunofluorescence, Western blotting, and transmission electron microscopy, to identify the mechanisms of regulation., Results: Our findings demonstrated that CERK-derived C1P played a protective role against HAPE. Inhibition of CERK exacerbated HAPE induced by the hypobaric hypoxic environment. Specifically, we identified a novel mechanism in which CERK inhibition induced aryl hydrocarbon receptor nuclear translocator-like (ARNTL) autophagic degradation, inducing the circadian rhythm and triggering mitochondrial damage by controlling the expression of proteins required for mitochondrial fission and fusion. The decreased ARNTL caused by CERK inhibition impaired mitochondrial dynamics, induced oxidative stress damage, and resulted in defects in mitophagy, particularly under hypoxia. Exogenous C1P prevented ARNTL degradation, alleviated mitochondrial damage, neutralized oxidative stress induced by CERK inhibition, and ultimately relieved HAPE., Conclusions: This study provides evidence for the protective effect of C1P against HAPE, specifically, through stabilizing circadian rhythms and maintaining mitochondrial dynamics. Exogenous C1P therapy may be a promising strategy for treating HAPE. Our findings also highlight the importance of the circadian rhythm and mitochondrial dynamics in the pathogenesis of HAPE, suggesting that targeting these pathways may be a potential therapeutic approach for this condition., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Production and hosting by Elsevier B.V.)

Super enhancers (SEs) are genomic regions comprising multiple closely spaced enhancers, typically occupied by a high density of cell-type-specific master transcription factors (TFs) and frequently enriched in key oncogenes in various tumors, including neuroblastoma (NB), one of the most prevalent malignant solid tumors in children originating from the neural crest. Cyclin-dependent kinase 5 regulatory subunit-associated protein 3 (CDK5RAP3) is a newly identified super-enhancer-driven gene regulated by master TFs in NB; however, its function in NB remains unclear. Through an integrated study of publicly available datasets and microarrays, we observed a significantly elevated CDK5RAP3 expression level in NB, associated with poor patient prognosis. Further research demonstrated that CDK5RAP3 promotes the growth of NB cells, both in vitro and in vivo. Mechanistically, defective CDK5RAP3 interfered with the UFMylation system, thereby triggering endoplasmic reticulum (ER) phagy. Additionally, we provide evidence that CDK5RAP3 maintains the stability of MEIS2, a master TF in NB, and in turn, contributes to the high expression of CDK5RAP3. Overall, our findings shed light on the molecular mechanisms by which CDK5RAP3 promotes tumor progression and suggest that its inhibition may represent a novel therapeutic strategy for NB., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Bone formation and homeostasis are greatly dependent on the osteogenic differentiation of human bone marrow stem cells (BMSCs). Therefore, revealing the mechanisms underlying osteogenic differentiation of BMSCs will provide new candidate therapeutic targets for osteoporosis., Methods: The osteogenic differentiation of BMSCs was measured by analyzing ALP activity and expression levels of osteogenic markers. Cellular Fe and ROS levels and cell viability were applied to evaluate the ferroptosis of BMSCs. qRT-PCR, Western blotting, and co-immunoprecipitation assays were harnessed to study the molecular mechanism., Results: The mRNA level of CRYAB was decreased in the plasma of osteoporosis patients. Overexpression of CRYAB increased the expression of osteogenic markers including OCN, OPN, RUNX2, and COLI, and also augmented the ALP activity in BMSCs, on the contrary, knockdown of CRYAB had opposite effects. IP-MS technology identified CRYAB-interacted proteins and further found that CRYAB interacted with ferritin heavy chain 1 (FTH1) and maintained the stability of FTH1 via the proteasome mechanism. Mechanically, we unraveled that CRYAB regulated FTH1 protein stability in a lactylation-dependent manner. Knockdown of FTH1 suppressed the osteogenic differentiation of BMSCs, and increased the cellular Fe and ROS levels, and eventually promoted ferroptosis. Rescue experiments revealed that CRYAB suppressed ferroptosis and promoted osteogenic differentiation of BMSCs via regulating FTH1. The mRNA level of FTH1 was decreased in the plasma of osteoporosis patients., Conclusions: Downregulation of CRYAB boosted FTH1 degradation and increased cellular Fe and ROS levels, and finally improved the ferroptosis and lessened the osteogenic differentiation of BMSCs.

Plant invasions and microplastics (MPs) have significantly altered the structure and function of aquatic habitats worldwide, resulting in severe damage to aquatic ecosystem health. However, the effects of MPs on plant invasion and the underlying mechanisms remain largely unknown. In this study, we conducted mesocosm experiments over a 90-day period to assess the effects of polystyrene microplastics on the invasion of exotic submerged macrophytes, sediment physicochemical properties, and sediment bacterial communities. Our results showed that PS-MPs significantly promoted the performance of functional traits and the invasive ability of exotic submerged macrophytes, while native plants remained unaffected. Moreover, PS-MPs addition significantly decreased sediment pH while increasing sediment carbon and nitrogen content. Additionally, MPs increased the diversity of sediment bacterial community but inhibited its structural stability, thereby impacting sediment bacterial multifunctionality to varying degrees. Importantly, we identified sediment properties, bacterial composition, and bacterial multifunctionality as key mediators that greatly enhance the invasion of exotic submerged macrophytes. These findings provide compelling evidence that the increase in MPs may exacerbate the invasion risk of exotic submerged macrophytes through multiple pathways. Overall, this study enhances our understanding of the ecological impacts of MPs on aquatic plant invasion and the health of aquatic ecosystems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Colorectal cancer (CRC) is one of the most commonly diagnosed malignant tumours of the digestive tract, and new therapeutic targets and prognostic markers are still urgently required. However, the role and molecular mechanisms of ATP binding cassette subfamily A member 8 (ABCA8) in CRC remain unclear., Methods: Databases and clinical specimens were analysed to determine the expression level of ABCA8 in CRC. Colony formation, CCK-8 and Transwell assays were conducted to determine cell proliferation, viability, migration and invasion. Flow cytometry was used to detect cell cycle progression and apoptosis. Western blot and rescue experiments were performed to determine the specific mechanisms of action of ABCA8., Results: ABCA8 expression is dramatically down-regulated in CRC tissues and cell lines. Ectopic expression of ABCA8 induced apoptosis and cell cycle arrest in vitro, inhibited cell growth, suppressed migration and invasion, reversed epithelial-mesenchymal transition and suppressed xenograft tumour growth and metastasis in vivo. Mechanistically, ABCA8 inhibited CRC cell proliferation and metastasis through the Wnt/β-catenin signalling pathway, both in vitro and in vivo., Conclusion: We verified that ABCA8 inhibits the malignant progression of CRC through the Wnt/β-catenin pathway. This newly discovered ABCA8-Wnt-β-catenin signalling axis is probably helpful in guiding the clinical diagnosis and treatment of CRC., Competing Interests: Conflict of interest None., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Human milk contains a variety of microorganisms that exert benefit for human health. In the current study, we isolated a novel Lactobacillus gasseri strain named Lactobacillus gasseri (L. gasseri) SHMB 0001 from human milk and aimed to evaluate the probiotic characteristics and protective effects on murine colitis of the strain. The results showed that L. gasseri SHMB 0001 possessed promising potential probiotic characteristics, including good tolerance against artificial gastric and intestinal fluids, adhesion to Caco-2 cells, susceptibility to antibiotic, no hemolytic activity, and without signs of toxicity or infection in mice. Administration of L. gasseri SHMB 0001 (1 × 10 8  CFU per gram of mouse weight per day) reduced weight loss, the disease activity index, and colon shortening in mice during murine colitis conditions. Histopathological analysis revealed that L. gasseri SHMB 0001 treatment attenuated epithelial damage and inflammatory infiltration in the colon. L. gasseri SHMB 0001 treatment increased the expression of colonic occludin and claudin-1 while decreasing the expression of pro-inflammatory cytokine genes. L. gasseri SHMB 0001 modified the composition and structure of the gut microbiota community and partially recovered the Clusters of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways altered by dextran sulfate sodium (DSS). Overall, our results indicated that the human breast milk-derived L. gasseri SHMB 0001 exhibited promising probiotic properties and ameliorative effect on DSS-induced colitis in mice. L. gasseri SHMB 0001 may be applied as a promising probiotic against intestinal inflammation in the future. PRACTICAL APPLICATION: L. gasseri SHMB 0001 isolated from human breast milk showed good tolerance to gastrointestinal environment, safety, and protective effect against DSS-induced mice colitis via enforcing gut barrier, downregulating pro-inflammatory cytokines, and modulating gut microbiota. L. gasseri SHMB 0001 may be a promising probiotic candidate for the treatment of intestinal inflammation., (© 2024 Institute of Food Technologists.)

Neuroblastoma (NB) is a common childhood tumor with a high incidence worldwide. The regulatory role of RNA N6-methyladenosine (m6A) in gene expression has attracted significant attention, and the impact of methyltransferase-like 14 (METTL14) on tumor progression has been extensively studied in various types of cancer. However, the specific influence of METTL14 on NB remains unexplored. Using data from the Target database, our study revealed significant upregulation of METTL14 expression in high-risk NB patients, with strong correlation with poor prognosis. Furthermore, we identified ETS1 and YY1 as upstream regulators that control the expression of METTL14. In vitro experiments involving the knockdown of METTL14 in NB cells demonstrated significant inhibition of cell proliferation, migration, and invasion. In addition, suppressing METTL14 inhibited NB tumorigenesis in nude mouse models. Through MeRIP-seq and RNA-seq analyses, we further discovered that YWHAH is a downstream target gene of METTL14. Mechanistically, we observed that methylated YWHAH transcripts, particularly those in the 5' UTR, were specifically recognized by the m6A "reader" protein YTHDF1, leading to the degradation of YWHAH mRNA. Moreover, the downregulation of YWHAH expression activated the PI3K/AKT signaling pathway, promoting NB cell activity. Overall, our study provides valuable insights into the oncogenic effects of METTL14 in NB cells, highlighting its role in inhibiting YWHAH expression through an m6A-YTHDF1-dependent mechanism. These findings also suggest the potential utility of a biomarker panel for prognostic prediction in NB patients., (© 2024. The Author(s).)

Stag beetles (Coleoptera: Lucanidae) represent a significant saproxylic assemblage in forest ecosystems and are noted for their enlarged mandibles and male polymorphism. Despite their relevance as ideal models for the study of exaggerated mandibles that aid in attracting mates, the regulatory mechanisms associated with these traits remain understudied, and restricted by the lack of high-quality reference genomes for stag beetles. To address this limitation, we successfully assembled the first chromosome-level genome of a representative species Dorcus hopei. The genome was 496.58 Mb in length, with a scaffold N50 size of 54.61 Mb, BUSCO values of 99.8%, and 96.8% of scaffolds anchored to nine pairs of chromosomes. We identified 285.27 Mb (57.45%) of repeat sequences and annotated 11,231 protein-coding genes. This genome will be a valuable resource for further understanding the evolution and ecology of stag beetles, and provides a basis for studying the mechanisms of exaggerated mandibles through comparative analysis., (© 2024. The Author(s).)

Rapid global urbanization has resulted in increased biodiversity problems, particularly the loss of ground-dwelling fauna in urban areas. Urban riparian corridors are an important green infrastructure for biodiversity conservation, in which urban vegetation plays an essential role. The influence of urban vegetation on ground-dwelling faunal diversity is poorly understood. In this study, we used camera traps to collect the species, functional and phylogenetic diversity of ground-dwelling fauna in the Wenyu River-North Canal riparian corridor in Beijing, and analyzed the effects of the vegetation structure and plant community composition on the diversity and community composition of ground-dwelling animals. A plant-ground dwelling animal interaction network was also built to investigate the food supply of plants for ground-nesting animals. We found that at the vegetation structure level, the high connectivity within a radius of 2000 m and the homogeneous distribution within a radius of 1000 m of vegetation patches had generally positive effects on ground-dwelling animals, and shrublands exhibited a supportive role for mammals in riparian corridors. At the plant community level, tall herbs were instrumental in increasing the willingness of ground-dwelling animals to stay in and pass through the area. Native plants were the main plant food resource for ground-dwelling animals. Given the significant effects of vegetation on ground-dwelling fauna, we advocate that habitat conservation and food supply for ground-dwelling animals be supported through appropriate plant landscape planning and design strategies in ecological corridors in urban areas in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Necroptosis triggered by H 2 O 2 is hypothesized to be a critical factor in the rupture of atherosclerotic plaques, which may precipitate acute cardiovascular events. Nevertheless, the specific regulatory molecules of this development remain unclear. We aims to elucidate a mechanism from the perspective of circular RNA., Objectives: There are few studies on circRNA in VSMCs necroptosis. The objective of our research is to shed light on the intricate roles that circHIPK3 plays in the process of necroptosis in VSMCs and the development of atherosclerotic plaques that are prone to rupture. Our study elucidates the specific molecular mechanisms by which circHIPK3 regulates necroptosis and atherosclerotic vulnerable plaque formation through targeted proteins. Identifying this mechanism at the cellular level offers a molecular framework for understanding plaque progression and stability regulation, as well as a potential biomarker for the prognosis of susceptible atherosclerotic plaques., Methods: We collected clinical vascular tissue for HE staining and Masson staining to determine the presence and stability of plaques. Then, NCBI database was used to screen out circRNA with elevated expression level in plaque tissue, and the up-regulated circRNA, circHIPK3, was verified by qRT-PCR and FISH. Further, we synthesized circHIPK3's small interference sequence and overexpressed plasmid in vitro, and verified its regulation effect on necroptosis of VSMCs under physiological and pathological conditions by WB, qRT-PCR and PI staining. Through RNA pull down, mass spectrometry and RNA immunoprecipitation, DRP1 was identified as circHIPK3 binding protein and was positively regulated by circHIPK3. Meanwhile, on the basis of silencing of DRP1, the regulation of circHIPK3 on necroptosis is verified to be mediated by DRP1. Finally, we validated the regulation of circHIPK3 on vulnerable plaque formation in ApoE -/- mice., Results: We investigated that circHIPK3 was highly expressed in vulnerable plaques, and the increase in expression level promoted H 2 O 2 induced necroptosis of VSMCs. CircHIPK3 targeted the protein DRP1, leading to an elevation in mitochondrial division rate, resulting in increased reactive oxygen species and impaired mitochondrial function, ultimately leading to necroptosis of VSMCs and vulnerable plaque formation., Conclusion: CircHIPK3 interact with DRP1 involve in H 2 O 2 induced Mitochondrial damage and necroptosis of VSMCs, and Silencing circHIPK3 in vivo can reduce atherosclerotic vulnerable plaque formation. Our research findings may have applications in providing diagnostic biomarkers for vulnerable plaques., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Production and hosting by Elsevier B.V.)

Rationale and Objectives: This study aimed to investigate the structural and functional alterations occurring within bilateral premotor thalamus (mPMtha) in motor subtypes of Parkinson's disease (PD)., Materials and Methods: Sixty-one individuals with instability and gait difficulty (PIGD) subtype, 60 individuals with tremor-dominant (TD) subtype and 66 healthy controls (HCs) participated in the study. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) and 3D T1-weighted (3DT1) scans. Functional connectivity (FC) analysis and Voxel-based morphometry (VBM) analysis were performed to evaluate the function and volume of mPMtha. Additionally, correlations between motor performance and FC values, volumes were examined separately. Support vector machine (SVM) model based on FC values and thalamic volumes was conducted to assist in the clinical diagnosis of PD motor subtype., Results: Compared to HCs and PIGD, TD subtype showed increased FC between the bilateral mPMtha and left middle occipital gyrus, left inferior parietal lobule (IPL). While PIGD subtype demonstrated decreased FC between right mPMtha and precentral gyrus (PreCG), supramarginal, IPL and superior parietal lobule. FC of bilateral mPMtha with the identified regions were significantly correlated with motor performance scores in PD patients. The SVM classification based on FC values demonstrated a high level of efficiency (AUC=0.874). The volumes of the bilateral mPMtha were indifferent among three groups., Conclusion: We noted distinct FC alterations of mPMtha in TD and PIGD subtypes, and these changes were correlated with motor performance. Furthermore, the machine learning based on statistically significant FC might be served as an alternative approach for automatically classifying PD motor subtypes individually., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background and Aims: Pseudomonas aeruginosa (P. aeruginosa) infections are strongly linked to the development of cardiovascular disease and atherosclerosis; however, the underlying mechanisms remain unclear. We previously confirmed that the flagellar hook protein FlgE in P. aeruginosa has immunostimulatory effects. This study investigated the effects and mechanisms of action of FlgE on atherogenesis., Methods: ApoE -/- mice were intravenously challenged with FlgE or FlgEM recombinant proteins for eight weeks. A murine model of chronic lung colonization was established using beads containing either mutable- or wild-type bacteria. Aortic sinus sections were stained to assess atherosclerosis progression. THP-1 macrophages exposed to FlgE or FlgEM were evaluated for their effects on lipid uptake and inflammation in vitro. Western blotting and pull-down assays were used to identify the binding proteins and signaling pathways involved, and specific blocking experiments were performed to confirm these effects., Results: FlgE accelerated atherosclerosis progression by triggering lipid deposition and inflammatory responses in high-fat diet (HFD)-fed ApoE -/- mice. In comparison to infection with wild-type PAO1, infection with PAO1/flgEΔBmF resulted in reduced atherosclerosis. Mechanistic analysis indicated that FlgE exacerbated lipoprotein uptake and foam cell formation by upregulating SR-A1 expression. Moreover, FlgE activated NF-κB and MAPK signaling, which subsequently led to inflammatory responses in THP-1-derived macrophages. Pull-down assays revealed that FlgE directly interacted with ATP5B, whereas blocking ATP5B attenuated FlgE-induced responses in macrophages., Conclusions: FlgE induces macrophage lipid uptake and pro-inflammatory responses mediated by ATP5B/NF-kB/AP-1 signaling, which eventually results in atherosclerosis. These findings support the development of therapeutic strategies for P. aeruginosa infection-induced atherosclerosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The study aimed to investigate the characteristics of brain functional network disruption in patients with systemic lupus erythematosus (SLE) with different cognitive function states by using graph theory analysis and to explore their relationship with clinical data and neuropsychiatric scales., Methods: Resting-state functional magnetic resonance imaging data were collected from 38 female SLE patients and 44 healthy controls. Based on Montreal Cognitive Assessment (MoCA) scores, SLE patients were divided into a high MoCA group (MoCA-H; MoCA score, ≥26) and a low MoCA group (MoCA-L; MoCA score, <26). The matrix of resting-state functional brain networks of subjects in the 3 groups was constructed by using the graph theory approach. The topological properties of the functional brain networks, including global and local metrics, in the 3 groups were calculated. The differences in the topological properties of networks between the 3 groups were compared. In addition, Spearman correlation analysis was used to explore the correlation between altered topological properties of brain networks and clinical indicators, as well as neuropsychiatric scales in SLE patients in the MoCA-L group., Results: At the global level, in the sparsity threshold range of 0.10 to 0.34, the values of small-world properties were greater than 1 in all 3 groups, indicating that functional brain networks of both 3 groups had small-world properties. There were statistically significant differences in the characteristic path length, global, and local efficiency between 3 groups ( F = 3.825, P = 0.0260; F = 3.722, P = 0.0285; and F = 3.457, P = 0.0364, respectively). Systemic lupus erythematosus patients in the MoCA-L group showed increased characteristic path length ( t = 2.816, P = 0.00651), decreased global ( t = -2.729, P = 0.00826), and local efficiency ( t = -2.623, P = 0.0109) compared with healthy controls. No statistically significant differences in local metrics were found between the MoCA-H group and the healthy control, MoCA-L groups. At the local level, there was statistically significant difference in the node efficiency among the 3 groups ( P < 0.05 after Bonferroni correction). Compared with healthy controls, SLE patients in the MoCA-L group showed decreased node efficiency in left anterior cingulate paracingulate gyrus, bilateral putamen, bilateral pallidum, and left Heschl gyrus. No statistically significant differences in the local metrics were found between the MoCA-H, MoCA-L, and healthy control groups. Correlation analysis in SLE patients in the MoCA-L group showed that the characteristic path length was positively correlated with C4 levels ( r = 0.587, P = 0.007), the global and local efficiencies were negatively correlated with C4 levels ( r = -0.599, P = 0.005; r = -0.599, P = 0.005, respectively), and the node efficiency in the bilateral putamen was negatively correlated with C4 levels ( r = -0.611, P = 0.004; r = -0.570, P = 0.009). The node efficiency in the left pallidum was negatively correlated with disease duration ( r = -0.480, P = 0.032). The node efficiency in the left Heschl gyrus was negatively correlated with IgM levels ( r = -0.478, P = 0.033). No correlation was noted between other network metrics, clinical indicators, and neuropsychological scales., Conclusions: The topological properties of functional brain networks were disrupted in SLE patients with low MoCA scores, suggesting that altered topological properties of the brain networks were associated with cognitive function in SLE patients. Correlation between altered topological properties of the brain networks and clinical indicators was noted in SLE patients with low MoCA scores, suggesting that altered topological properties of brain networks in SLE patients may have clinical significance as imaging markers for monitoring disease changes in patients with SLE., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)