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Cancer cells, as well as surrounding stromal and inflammatory cells, form an inflammatory tumor microenvironment (TME) to promote all stages of carcinogenesis. As an emerging post-translational modification (PTM) of serine and threonine residues of proteins, O-linked-N-Acetylglucosaminylation (O-GlcNAcylation) regulates diverse cancer-relevant processes, such as signal transduction, transcription, cell division, metabolism and cytoskeletal regulation. Recent studies suggest that O-GlcNAcylation regulates the development, maturation and functions of immune cells. However, the role of protein O-GlcNAcylation in cancer-associated inflammation has been less explored. This review summarizes the current understanding of the influence of protein O-GlcNAcylation on cancer-associated inflammation and the mechanisms whereby O-GlcNAc-mediated inflammation regulates tumor progression. This will provide a theoretical basis for further development of anti-cancer therapies.

Using traditional process to fabricate large scale titanium alloy thin-walled part such as wings and grid rudder, has the problem of low material utilization. Wire arc additive manufacturing (WAAM) is a flexible manufacturing technology with high deposition efficiency and high material utilization. In addition, a hot-wire device is attached to the WAAM system as auxiliary heat source, and the WAAM system becomes hot-wire arc additive manufacturing (HWAAM) system. In this paper, a large scale titanium alloy drone frame was fabricated by HWAAM. A double-side alternating deposition method was proposed to reduce the thermal deformation of the substrate. Two additional sections of the drone frame was taken off for mechanical analysis. The shape of the whole drone frame is completed and the mechanical properties meet the requirements of the project.

Coarse grains and gas pores are two main problems that limit the application of additive manufacturing aluminum alloys. To reduce porosity and refine grains, this paper presents a quantitative investigation into the effect of pulse frequency and arc current on the porosity and grains of arc additive manufacturing Al–5Si alloy. The experiment results show that pulse frequency and arc current have a significant impact on the macrostructure, microstructure, porosity, and tensile properties of the samples. Fine grains and a uniform microstructure can be obtained with low pulse frequency and low arc current as a result of the rapid cooling of the molten pool. With the increase of pulse frequency, density shows a trend that firstly escalates and attains the maximum value at 50 Hz, but later declines as a result of the relation between pores formation and gas escape. Moreover, better tensile properties can be obtained at low pulse frequency and low arc current because of the finer grains.

Identifying alpha-fetal protein (AFP)-negative focal hepatic lesions presents a significant challenge, particularly in China. We sought to develop an economically portable tool for the diagnosis of benign and malignant liver lesions with AFP-negative status, and explore its clinical diagnostic efficiency. A retrospective study was conducted at Peking University Shenzhen Hospital from January 2017 to February 2023, including a total of 348 inpatients with AFP-negative liver space-occupying lesions. The study used a training set of 252 inpatients from January 2017 to September 2021 to establish a diagnostic model for differentiating benign and malignant AFP-negative liver space-occupying lesions. Additionally, a validation cohort of 96 inpatients from October 2021 to February 2023 was used to confirm the diagnostic performance of the model. From January 2017 to February 2023, patients at JingNing People's Hospital, Gansu Province were assigned to the external cohort ( = 78). A predictive tool was established by screening age, gender, hepatitis B virus (HBV)/hepatitis C virus (HCV) infected, single lesion, alanine amino transferase (ALT), and lymphocyte-to-monocyte ratio (LMR) using multivariate logistic regression analysis and clinical practice. The area under the curve (AUC) of the model was 0.911 (95% CI [0.873-0.949]) in the training set and 0.882 (95% CI [0.815-0.949]) in the validation cohort. In addition, the model achieved an area under the curve of 0.811 (95% CI [0.687-0.935]) in the external validation cohort. Our results demonstrated that the predictive tool has the characteristics of good diagnostic efficiency, economy and convenience, which is helpful for the clinical triage and decision-making of AFP-negative liver space-occupying lesions.

Inflammation is a hallmark of intervertebral disc degeneration (IVDD) characterized by immune cell infiltration and cytokine secretion. Stage‐specific transcriptomic analyses of IVDD via single‐cell RNA sequencing (scRNA‐seq) have primarily focused on nucleus pulposus cell phenotypes but not immune subpopulations. In other disease contexts, integrating genome‐wide association studies (GWAS) with scRNA‐seq data has provided insights on pathomechanisms in relation to specific cellular subpopulations via single‐cell disease relevance scores (scDRS). However, such an approach remains to be applied to IVDD. Here, the stage‐ specific analysis of IVDD in relation to Pfirrmann grading revealed a key transition in immune cells from a preponderance of LCN2high myeloid‐derived suppressor cells (MDSCs) during early degeneration to a surge of proinflammatory IL1B+ macrophages in advanced IVDD. scDRS implicated IL1B+ M1‐like macrophages as a GWAS risk‐enriched subpopulation associated with disease, while functional validation indicated an immunomodulatory effect of LCN2high MDSCs via ANXA1‐mediated inflammation suppression. Accordingly, LCN2 knockout mice exhibit accelerated IVDD, whereas recombinant LCN2 promoted macrophage polarization in vitro to the reparative phenotype by enhancing ANXA1 / Arginase‐1 expression and countering LPS/IFN‐γ‐induced pro‐inflammatory phenotype. This work identifies LCN2high MDSCs as an immunoprotective subpopulation in early IVDD and highlights a potential role of LCN2 as a novel therapeutic agent. Inflammatory dysregulation drives intervertebral disc degeneration via stage‐dependent immune cellular dynamics. Single‐cell transcriptomics and genetic risk mapping revealed a shift from LCN2high myeloid‐derived suppressor cells maintaining disc repair in early stages to IL1B+ macrophage‐dominated pathology in advanced disease. Functional validation identified LCN2 as a critical immunomodulator, rescuing inflammatory imbalance via regulating ANXA1/Arginase‐1 expression, thus highlighting its therapeutic potential in degenerative disc disease.

The International Consensus on ANA Patterns (ICAP) recently codified the AC-30 nuclear pattern, characterized by fine speckled nuclear texture and metaphase chromatin staining. Although formally recognized, its clinical significance remains unclear. Quantitative methods and objective outcome measures for characterizing AC-30 have not been established. A retrospective analysis was conducted using archived HEp-2 ANA images. AC-30 was defined by unanimous scoring from three blinded experts. AC-1 and AC-2 served as comparator sets. Clinical diagnoses and serological data were retrieved from hospital records. Pixel classification was performed using ilastik, and per-nucleus intensity features were extracted with CellProfiler. Image-level separation was assessed by partitioning nuclei into high- and low-intensity groups via Isolation Forest. Statistical comparisons used Welch's t-tests and Spearman's rank correlation. The AC-30 group included 183 images (AC-1, n = 183; AC-2, n = 207). Within AC-30, 57.4% had non-AID or unknown diagnoses, 26.8% had other autoimmune diseases, and 15.8% had ANA-associated rheumatic disease (AARD). In ENA-negative AC-30, AARD accounted for 7.7% (6/78), compared to 18.3% (21/115) in ENA-negative AC-2. RA accounted for 16.9% (31/183) in AC-30, consistent across ENA strata. AC-30 displayed lower per-nucleus intensities than AC-2 (all p < 0.0001) and reduced per-image ΔMaxIntensity (0.177 vs. 0.252, p < 0.0001), while ΔMeanIntensity was similar (0.068 vs. 0.067, p = 0.549). AC-30 is quantitatively dimmer than AC-2, with reduced nuclear brightness and peak-intensity separation. In this retrospective cohort, ENA-negative AC-30 was associated with fewer AARD cases. RA accounted for ~17% of AC-30, and anti-CCP and RF remained informative markers. The ilastik-CellProfiler workflow enables auditable ANA quantification.

Evidence is mounting that chronic high‐fructose diets (HFrD) can lead to metabolic abnormalities and cause a variety of diseases. However, the underlying mechanism by which long‐term high fructose intake influencing systemic metabolism remains unclarified. This study, therefore, attempted to investigate the impact of a high‐fructose diet on metabolic profile. Four‐week‐old male C57BL/6 mice were fed with 15% fructose solution as their only source of water for 8 weeks. Afterward, gas chromatography–mass spectrometry (GC–MS) was employed to investigate the comprehensive metabolic profile of serum, muscle, liver, heart, white adipose, brain, and kidney tissues, and multivariate analyses including principal component analysis (PCA) and orthogonal partial least squared‐discriminant analysis (OPLS‐DA) were applied to screen for differential metabolite expression between the HFrD and control groups. Furthermore, the MetaboAnalyst 5.0 (http://www.metaboanalyst.ca) and Kyoto Encyclopedia of Genes and Genomes database (KEGG; http://www.kegg.jp) were employed to portray a detailed metabolic network. This study identified 62 metabolites related to HFrD and 10 disturbed metabolic pathways. The results indicated that high fructose intake mainly influenced amino acid metabolism and biosynthesis (glycine, serine, and threonine metabolism; aspartate, and glutamate metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis, and arginine biosynthesis pathways), glutathione metabolism, sphingolipid metabolism, and glyoxylate and dicarboxylate metabolism in serum, whereas these pathways were suppressed in the brain. Starch and sucrose metabolism in muscle was also disrupted. These results elucidate the effects of long‐term high fructose consumption on the metabolic profiles of various tissues and provide new insight for the identification of potential metabolic biomarkers and pathways disrupted by high fructose.

BET1 encodes a Golgi-associated membrane protein involved in vesicular transport from the endoplasmic reticulum (ER) to the Golgi apparatus. While the role of BET1 in cancer development remains poorly understood, its function in glioblastoma multiforme (GBM) has not been systematically investigated. In this study, we found that 15 out of 33 cancer types showed significant differential BET1 expression between tumor and normal tissues. Furthermore, survival analysis identified BET1 as an independent prognostic factor in GBM. Additional analyses revealed correlations between BET1 expression and the infiltration of immune cells, such as Tregs and CD4 + T cells, in GBM. Moreover, BET1 knockdown in glioblastoma cells reduced their proliferation and migration capacities. This study provides a comprehensive analysis of BET1, thereby advancing our understanding of its oncogenic potential in GBM.

BCL-2 has been implicated in prostate cancer (PCa) progression and development of castration-resistant disease (CRPC); however, it remains unclear how the BCL-2- and AR-expressing PCa cell populations evolve across the PCa continuum, how AR molecularly regulates BCL-2 and whether BCL-2 represents a common therapeutic target in heterogeneous CRPC. Here we first show the selective induction of BCL-2 by AR pathway inhibitors (ARPIs). Vectra-based quantitative multiplex immunofluorescence (qmIF) and image mass cytometry (IMC) analyses with single-cell resolution in patient PCa and xenograft models reveal markedly increased BCL-2 + (AR + or AR - ) PCa cells in CRPC. Mechanistically, AR represses BCL-2 transcription through several AR binding sites and ARPIs relieve this repression. Therapeutic studies in cells, organoids and xenografts support BCL-2 as a shared vulnerability across diverse CRPC subtypes. A Phase Ib clinical trial (NCT03751436) combining enzalutamide and BCL-2 inhibitor venetoclax demonstrated reduced circulating tumor cells in responding patients. In summary, by integrating high-content single-cell level imaging analyses with mechanistic studies, extensive preclinical therapeutic experiments and a Phase Ib clinical trial, our studies herein elucidate the AR +/- BCL-2 +/- PCa cell subpopulation dynamics and credentials BCL-2 as a vital therapeutic target in heterogeneous CRPC.