BIGH3 mediates apoptosis and gap junction failure in osteocytes during renal cell carcinoma bone metastasis progression.

Renal cell carcinoma (RCC) bone metastatis progression is driven by crosstalk between tumor cells and the bone microenvironment, which includes osteoblasts, osteoclasts, and osteocytes. RCC bone metastases (RCCBM) are predominantly osteolytic and resistant to antiresorptive therapy. The molecular mechanisms underlying pathologic osteolysis and disruption of bone homeostasis remain incompletely understood. We previously reported that BIGH3/TGFBI (transforming growth factor-beta-induced protein ig-h3, shortened to BIGH3 henceforth) secreted by colonizing RCC cells drives osteolysis by inhibiting osteoblast differentiation, impairing healing of osteolytic lesions, which is reversible with osteoanabolic agents. Here, we report that BIGH3 induces osteocyte apoptosis in both human RCCBM tissue specimens and in a preclinical mouse model. We also demonstrate that BIGH3 reduces Cx43 expression, blocking gap junction (GJ) function and osteocyte network communication. BIGH3-mediated GJ inhibition is blocked by the lysosomal inhibitor hydroxychloroquine (HCQ), but not osteoanabolic agents. Our results broaden the understanding of pathologic osteolysis in RCCBM and indicate that targeting the BIGH3 mechanism could be a combinational strategy for the treatment of RCCBM-induced bone disease that overcomes the limited efficacy of antiresorptives that target osteoclasts.

Molecular Photoelectrochemical Energy Storage Materials for Coupled Solar Batteries.

ConspectusSolar-to-electrochemical energy storage is one of the essential solar energy utilization pathways alongside solar-to-electricity and solar-to-chemical conversion. A coupled solar battery enables direct solar-to-electrochemical energy storage via photocoupled ion transfer using photoelectrochemical materials with light absorption/charge transfer and redox capabilities. Common photoelectrochemical materials face challenges due to insufficient solar spectrum utilization, which restricts their redox potential window and constrains energy conversion efficiency. In contrast, molecular photoelectrochemical energy storage materials are promising for their mechanism of exciton-involved redox reaction that allows for extra energy utilization from hot excitons generated by superbandgap excitation and localized heat after absorption of sub-bandgap photons. This enables more efficient redox reactions with a less restricted redox potentials window and, thus, better utilization of the full solar spectrum. Despite these advantages, practical application remains elusive due to the mismatch between the short lifetime of the charge separation state (µs). This mismatch results in a significant portion of the photogenerated charges recombining before participating in desired electrochemical energy storage reactions, leading to diminished overall efficiency. It is therefore highly important to develop molecular materials with intrinsic prolonged charge separation state and extrinsic effective mass-electron transfer to enable efficient coupled solar batteries for practical applications.In this Account, we begin with an introduction of the general solar-to-electrochemical energy storage concept based on molecular photoelectrochemical energy storage materials, highlighting the advantages of periodic oxidative donor-reductive acceptor porous aggregate structures that have synergistic implications on charge separation state lifetime extension and mass-electron transfer. We then present our earliest trial on the design and application of molecular photoelectrochemical energy storage materials, which stimulated our subsequent studies on tuning electron donor and acceptor structures for enhanced charge separation and diverse photoelectrochemical redox reactions. Moreover, we introduce the best practices in the design and assembly of various coupled solar battery devices, along with our literature contributions and progresses in solar-to-electrochemical energy storage efficiency (ηSES) over nearly the past decade. Finally, we conclude by highlighting the universality of our strategies as essential design principles, spanning from regulating long-lived charge separation states and photocoupled ion transfer processes in molecular materials to the construction of efficient coupled solar batteries. We offer perspectives on the synergy between photovoltage and redox potentials and the practical significance of 3D printing, providing key evaluation indicators for large-scale application. This Account provides molecular level insights for the construction of high-efficiency photoelectrochemical energy storage materials and guidance for practical solar-to-electrochemical energy storage applications.

Low-frequency ERK and Akt activity dynamics are predictive of stochastic cell division events.

Understanding the dynamics of intracellular signaling pathways, such as ERK1/2 (ERK) and Akt1/2 (Akt), in the context of cell fate decisions is important for advancing our knowledge of cellular processes and diseases, particularly cancer. While previous studies have established associations between ERK and Akt activities and proliferative cell fate, the heterogeneity of single-cell responses adds complexity to this understanding. This study employed a data-driven approach to address this challenge, developing machine learning models trained on a dataset of growth factor-induced ERK and Akt activity time courses in single cells, to predict cell division events. The most predictive models were developed by applying discrete wavelet transforms (DWTs) to extract low-frequency features from the time courses, followed by using Ensemble Integration, a data integration and predictive modeling framework. The results demonstrated that these models effectively predicted cell division events in MCF10A cells (F-measure=0.524, AUC=0.726). ERK dynamics were found to be more predictive than Akt, but the combination of both measurements further enhanced predictive performance. The ERK model`s performance also generalized to predicting division events in RPE cells, indicating the potential applicability of these models and our data-driven methodology for predicting cell division across different biological contexts. Interpretation of these models suggested that ERK dynamics throughout the cell cycle, rather than immediately after growth factor stimulation, were associated with the likelihood of cell division. Overall, this work contributes insights into the predictive power of intra-cellular signaling dynamics for cell fate decisions, and highlights the potential of machine learning approaches in unraveling complex cellular behaviors.

Combining Flexible Region Design and Automatic Design to Enhance the Thermal Stability and Catalytic Efficiency of Leucine Dehydrogenase.

Leucine dehydrogenase (LeuDH, EC 1.4.1.9) can reversibly catalyze the oxidative deamination of l-leucine and some other specific α-amino acids to form the corresponding α-ketoacids. This reaction has great significance in the field of food additives and the pharmaceutical industry. The LeuDH from Exiguobacterium sibiricum (EsLeuDH) has high catalytic efficiency but limited thermal stability, hindering its widespread industrial application. In this study, a mutant N5F/I12L/A352Y of EsLeuDH (referred to as M2) was developed with enhanced thermal stability and catalytic activity through rational modification. The M2 mutant exhibits a half-life at 60 °C (t1/2(60 °C)) of 975.7 min and a specific activity of 69.6 U mg-1, which is 5.4 and 2.1 times higher than those of EsLeuDH, respectively. This research may facilitate the utilization of EsLeuDH at elevated temperatures, enhancing its potential for industrial applications. The findings offer a practical and efficient approach for optimizing LeuDH and other industrial enzymes.

Sex differences in correlates of suicide attempts in Chinese Han first-episode and drug-naïve major depressive disorder with comorbid subclinical hypothyroidism: A cross-sectional study.

BACKGROUND: This study aimed to investigate sex differences in risk factors for suicide attempts in first-episode and drug naive (FEDN) major depressive disorder (MDD) with comorbid subclinical hypothyroidism (SCH). METHODS: A total of 1034 FEDN MDD patients with comorbid SCH were enrolled. The Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) positive subscale were used to assess patients' symptoms. Thyroid hormone levels and metabolic parameters were measured. RESULTS: MDD patients with SCH had a significantly higher risk of suicide attempts than those without SCH (25.4% vs. 12.2%). Logistic regression showed that HAMA score, thyroid stimulating hormone (TSH) levels, and thyroid peroxidase antibody (TPOAb) levels were significantly associated with an increased risk for suicide attempts in both male and female MDD patients comorbid SCH, while low-density lipoprotein cholesterol (LDL-C) was significantly associated with an increased risk for suicide attempts only in male patients, HAMD score and systolic blood pressure were significantly associated with an increased risk for suicide attempts only in female patients. CONCLUSION: SCH comorbidities may increase suicide attempts in MDD patients. Our results showed significant sex differences in clinical and metabolic factors associated with suicide attempts among FEDN MDD patients with comorbid SCH, highlighting appropriate sex-based preventive interventions are needed.

Unbiased metastatic niche-labeling identifies estrogen receptor-positive macrophages as a barrier of T cell infiltration during bone colonization.

Microenvironment niches determine cellular fates of metastatic cancer cells. However, robust and unbiased approaches to identify niche components and their molecular profiles are lacking. We established Sortase A-Based Microenvironment Niche Tagging (SAMENT), which selectively labels cells encountered by cancer cells during metastatic colonization. SAMENT was applied to multiple cancer models colonizing the same organ and the same cancer to different organs. Common metastatic niche features include macrophage enrichment and T cell depletion. Macrophage niches are phenotypically diverse between different organs. In bone, macrophages express the estrogen receptor alpha (ERα) and exhibit active ERα signaling in male and female hosts. Conditional knockout of Esr1 in macrophages significantly retarded bone colonization by allowing T cell infiltration. ERα expression was also discovered in human bone metastases of both genders. Collectively, we identified a unique population of ERα+ macrophages in the metastatic niche and functionally tied ERα signaling in macrophages to T cell exclusion during metastatic colonization. HIGHLIGHTS: SAMENT is a robust metastatic niche-labeling approach amenable to single-cell omics.Metastatic niches are typically enriched with macrophages and depleted of T cells.Direct interaction with cancer cells induces ERα expression in niche macrophages. Knockout of Esr1 in macrophages allows T cell infiltration and retards bone colonization.

Coordination cages integrated into swelling poly(ionic liquid)s for guest encapsulation and separation.

Coordination cages have been widely reported to bind a variety of guests, which are useful for chemical separation. Although the use of cages in the solid state benefits the recycling, the flexibility, dynamicity, and metal-ligand bond reversibility of solid-state cages are poor, preventing efficient guest encapsulation. Here we report a type of coordination cage-integrated solid materials that can be swelled into gel in water. The material is prepared through incorporation of an anionic FeII4L6 cage as the counterion of a cationic poly(ionic liquid) (MOC@PIL). The immobilized cages within MOC@PILs have been found to greatly affect the swelling ability of MOC@PILs and thus the mechanical properties. Importantly, upon swelling, the uptake of water provides an ideal microenvironment within the gels for the immobilized cages to dynamically move and flex that leads to excellent solution-level guest binding performances. This concept has enabled the use of MOC@PILs as efficient adsorbents for the removal of pollutants from water and for the purification of toluene and cyclohexane. Importantly, MOC@PILs can be regenerated through a deswelling strategy along with the recycling of the extracted guests.

A study on satisfaction evaluation of Chinese mainstream short video platforms based on grounded theory and CRITIC-VIKOR.

In recent years, Chinese short video platforms have experienced vigorous development, accompanied by increasing expectations and demands from users. This study aims to explore the factors influencing user satisfaction on mainstream Chinese short video platforms and provide a scientific and objective evaluation framework to support the enhancement of user satisfaction and the development of short video platforms. Through a combination of qualitative and quantitative research methods, multiple mainstream Chinese short video platforms were evaluated and analyzed. Firstly, semi-structured interviews with users were conducted using Grounded Theory to delve into the key factors shaping users' expectations, needs, and satisfaction towards short video platforms. Secondly, the CRITIC-VIKOR method was employed to assign comprehensive weights to various factors and to evaluate the satisfaction levels of the mainstream platforms. The study revealed that the core categories affecting user satisfaction include content quality and interaction, trust and values, and user experience. The weighted values of the main categories are as follows: interface and interaction design 0.124, personalized experience 0.115, platform stability and performance 0.075, privacy and security 0.133, user service and communication 0.060, social impact and values 0.124, content quality and diversity 0.088, social interaction 0.094, and advertising experience 0.186. Furthermore, the satisfaction evaluation of mainstream short video platforms indicated that bilibili platform garnered the highest user satisfaction among surveyed users. This study provides specific directions for improving user experience and enhancing user satisfaction for short video platforms, while also offering a evaluation framework based on Grounded Theory and CRITIC-VIKOR method for similar studies, thus expanding the theoretical and practical fields of user satisfaction research.

Sex differences and risk factors of self-reported suicide attempts in middle-aged Chinese Han patients with first-episode drug-naïve anxious depression: a large-scale cross-sectional study.

This study aims to investigate sex differences and risk factors for self-reported suicide attempts among Chinese Han middle-aged patients with first-episode drug-naïve (FEDN) anxious depression (AD). A total of 1796 patients with FEDN major depressive disorder were enrolled in this study, including 341 middle-aged patients with AD. We compared the prevalence, demographics, and clinical characteristics of suicide attempts between male and female patients with FEDN middle-aged AD. We also explored the risk factors for self-reported suicide attempts in this population using binary logistic regression analysis. The male/female ratio was 91/250 and the age of onset was 51.50 ± 4.13. Our results showed that there were no significant sex differences in the prevalence of self-reported suicide attempts in middle-aged patients with FEDN AD. However, we did find significant differences in several demographic and clinical characteristics between self-reported suicide attempters and non-suicide attempters. Moreover, severe anxiety, measured by the Hamilton Anxiety Rating Scale score, was identified as a risk factor for self-reported suicide attempts in female middle-aged AD patients. Additionally, elevated thyroid peroxidase antibody (TPOAb) levels were linked to self-reported suicide attempts in male AD patients. Our findings suggest that there are no significant sex differences in the prevalence of self-reported suicide attempts in this population, but there may be sex-specific risk factors for self-reported suicide attempts in middle-aged AD. Clinical psychiatrists need to pay attention to thyroid hormone levels in middle-aged anxious depression.

Targeting squalene epoxidase restores anti-PD-1 efficacy in metabolic dysfunction-associated steatohepatitis-induced hepatocellular carcinoma.

OBJECTIVE: Squalene epoxidase (SQLE) promotes metabolic dysfunction-associated steatohepatitis-associated hepatocellular carcinoma (MASH-HCC), but its role in modulating the tumour immune microenvironment in MASH-HCC remains unclear. DESIGN: We established hepatocyte-specific Sqle transgenic (tg) and knockout mice, which were subjected to a choline-deficient high-fat diet plus diethylnitrosamine to induce MASH-HCC. SQLE function was also determined in orthotopic and humanised mice. Immune landscape alterations of MASH-HCC mediated by SQLE were profiled by single-cell RNA sequencing and flow cytometry. RESULTS: Hepatocyte-specific Sqle tg mice exhibited a marked increase in MASH-HCC burden compared with wild-type littermates, together with decreased tumour-infiltrating functional IFN-γ+ and Granzyme B+ CD8+ T cells while enriching Arg-1+ myeloid-derived suppressor cells (MDSCs). Conversely, hepatocyte-specific Sqle knockout suppressed tumour growth with increased cytotoxic CD8+ T cells and reduced Arg-1+ MDSCs, inferring that SQLE promotes immunosuppression in MASH-HCC. Mechanistically, SQLE-driven cholesterol accumulation in tumour microenvironment underlies its effect on CD8+ T cells and MDSCs. SQLE and its metabolite, cholesterol, impaired CD8+ T cell activity by inducing mitochondrial dysfunction. Cholesterol depletion in vitro abolished the effect of SQLE-overexpressing MASH-HCC cell supernatant on CD8+ T cell suppression and MDSC activation, whereas cholesterol supplementation had contrasting functions on CD8+ T cells and MDSCs treated with SQLE-knockout supernatant. Targeting SQLE with genetic ablation or pharmacological inhibitor, terbinafine, rescued the efficacy of anti-PD-1 treatment in MASH-HCC models. CONCLUSION: SQLE induces an impaired antitumour response in MASH-HCC via attenuating CD8+ T cell function and augmenting immunosuppressive MDSCs. SQLE is a promising target in boosting anti-PD-1 immunotherapy for MASH-HCC.

CBP/P300 BRD Inhibition Reduces Neutrophil Accumulation and Activates Antitumor Immunity in TNBC.

Tumor-associated neutrophils (TANs) have been shown to promote immunosuppression and tumor progression, and a high TAN frequency predicts poor prognosis in triple-negative breast cancer (TNBC). Dysregulation of CREB binding protein (CBP)/P300 function has been observed with multiple cancer types. The bromodomain (BRD) of CBP/P300 has been shown to regulate its activity. In this study, we found that IACS-70654, a novel and selective CBP/P300 BRD inhibitor, reduced TANs and inhibited the growth of neutrophil-enriched TNBC models. In the bone marrow, CBP/P300 BRD inhibition reduced the tumor-driven abnormal differentiation and proliferation of neutrophil progenitors. Inhibition of CBP/P300 BRD also stimulated the immune response by inducing an IFN response and MHCI expression in tumor cells and increasing tumor-infiltrated CTLs. Moreover, IACS-70654 improved the response of a neutrophil-enriched TNBC model to docetaxel and immune checkpoint blockade. This provides a rationale for combining a CBP/P300 BRD inhibitor with standard-of-care therapies in future clinical trials for neutrophil-enriched TNBC.

A novel miR-466l-3p/FGF23 axis promotes osteogenic differentiation of human bone marrow mesenchymal stem cells.

BACKGROUND: MicroRNAs (miRNAs) regulate osteogenic differentiation processes and influence the development of osteoporosis (OP). This study aimed to investigate the potential role of miR-466 l-3p in OP. METHODS: The expression levels of miR-466 l-3p and fibroblast growth factor 23 (FGF23) were quantified in the trabeculae of the femoral neck of 40 individuals with or without OP using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The impact of miR-466 l-3p or FGF23 expression on cell proliferation and the expression levels of runt-related transcription factor 2 (RUNX2), type I collagen (Col1), osteocalcin (OCN), osterix (OSX) and dentin matrix protein 1 (DMP1) was quantified in human bone marrow mesenchymal stem cells (hBMSCs) overexpressing miR-466 l-3p. Furthermore, alkaline phosphatase (ALP) staining and alizarin red staining were performed to measure ALP activity and the levels of calcium deposition, respectively. In addition, bioinformatics analysis, luciferase reporter assays, and RNA pull-down assays were conducted to explore the molecular mechanisms underlying the effects of miR-466 l-3p and FGF23 in osteogenic differentiation of hBMSCs. RESULTS: The expression levels of miR-466 l-3p were significantly lower in femoral neck trabeculae of patients with OP than in the control cohort, whereas FGF23 levels exhibited the opposite trend. Furthermore, miR-466 l-3p levels were upregulated and FGF23 levels were downregulated in hBMSCs during osteogenic differentiation. Moreover, the high miR-466 l-3p expression enhanced the mRNA expression of RUNX2, Col1, OCN, OSX and DMP1, as well as cell proliferation, ALP activity, and calcium deposition in hBMSCs. FGF23 was found to be a direct target of miR-466 l-3p. FGF23 overexpression downregulated the expression of osteoblast markers and inhibited the osteogenic differentiation induced by miR-466 l-3p overexpression. qRT-PCR and Western blot assays showed that miR-466 l-3p overexpression decreased the expression levels of mRNAs and proteins associated with the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, whereas FGF23 upregulation exhibited the opposite trend. CONCLUSION: In conclusion, these findings suggest that miR-466 l-3p enhances the osteogenic differentiation of hBMSCs by suppressing FGF23 expression, ultimately preventing OP.

Feasibility and safety of contrast-enhanced magnetic resonance-guided adaptive radiotherapy for upper abdominal tumors: A preliminary exploration.

This study investigates the use of contrast-enhanced magnetic resonance (MR) in MR-guided adaptive radiotherapy (MRgART) for upper abdominal tumors. Contrast-enhanced T1-weighted MR (cT1w MR) using half doses of gadoterate was used to guide daily adaptive radiotherapy for tumors poorly visualized without contrast. The use of gadoterate was found to be feasible and safe in 5-fraction MRgART and could improve the contrast-to-noise ratio of MR images. And the use of cT1w MR could reduce the interobserver variation of adaptive tumor delineation compared to plain T1w MR (4.41 vs. 6.58, p < 0.001) and T2w MR (4.41 vs. 7.42, p < 0.001).

CrossZoom: Simultaneous Motion Deblurring and Event Super-Resolving.

Even though the collaboration between traditional and neuromorphic event cameras brings prosperity to frame-event based vision applications, the performance is still confined by the resolution gap crossing two modalities in both spatial and temporal domains. This paper is devoted to bridging the gap by increasing the temporal resolution for images, i.e., motion deblurring, and the spatial resolution for events, i.e., event super-resolving, respectively. To this end, we introduce CrossZoom, a novel unified neural Network (CZ-Net) to jointly recover sharp latent sequences within the exposure period of a blurry input and the corresponding High-Resolution (HR) events. Specifically, we present a multi-scale blur-event fusion architecture that leverages the scale-variant properties and effectively fuses cross-modal information to achieve cross-enhancement. Attention-based adaptive enhancement and cross-interaction prediction modules are devised to alleviate the distortions inherent in Low-Resolution (LR) events and enhance the final results through the prior blur-event complementary information. Furthermore, we propose a new dataset containing HR sharp-blurry images and the corresponding HR-LR event streams to facilitate future research. Extensive qualitative and quantitative experiments on synthetic and real-world datasets demonstrate the effectiveness and robustness of the proposed method. Codes and datasets are released at https://bestrivenzc.github.io/CZ-Net/.

A pillar-layered Ni2P-Ni5P4-CoP array derived from a metal-organic framework as a bifunctional catalyst for efficient overall water splitting.

Interfacial engineering emerges as a potent strategy for regulating the catalytic reactivity of metal phosphides. Developing a facile and cost-effective method to construct bifunctional metal phosphides for highly efficient electrochemical overall water splitting remains an essential and challenging issue. Here, a multiphase transition metal phosphide is constructed through the direct phosphorization of a Ni-Co metal-organic framework grown on nickel foam (Ni-Co-MOF/NF), which is prepared by utilizing nickel foam as conductive substrate and nickel source. The resulting transition metal phosphide manifests a pillar-layered morphology, wherein CoP, Ni2P, and Ni5P4 nanoparticles are embedded within each carbon sheet and these carbon sheets assemble into a pillar-shaped structure on the nickel foam (Ni2P-Ni5P4-CoP-C/NF). The heterogeneous Ni2P-Ni5P4-CoP-C/NF with multiple interfaces serves as a highly efficient bifunctional electrocatalyst with overpotentials of -100 mV and 293 mV in the hydrogen evolution reaction and oxygen evolution reaction, respectively, at 50 mA cm-2 in alkaline media. This superior catalytic performance should mainly be ascribed to its enriched active centers and multiphase synergy. When directly applied for alkaline overall water splitting, the Ni2P-Ni5P4-CoP-C/NF couple demonstrates satisfactory activity (1.55 V @10 mA cm-2) along with sustained durability over 18 hours. This method brings fresh enlightenment to the economical and controllable preparation of multi-metal phosphides for energy conversion.

Interfacial Engineering of MoS2@CoS2 Heterostructure Electrocatalysts for Effective pH-Universal Hydrogen Evolution Reaction.

The practical utilization of the hydrogen evolution reaction (HER) necessitates the creation of electrocatalysts that are both efficient and abundant in earth elements, capable of operating effectively within a wide pH range. However, this objective continues to present itself as an arduous obstacle. In this research, we propose the incorporation of sulfur vacancies in a novel heterojunction formed by MoS2@CoS2, designed to exhibit remarkable catalytic performances. This efficacy is attributed to the advantageous combination of the low work function and space charge zone at the interface between MoS2 and CoS2 in the heterojunction. The MoS2@CoS2 heterojunction manifests outstanding hydrogen evolution activity over an extensive pH range. Remarkably, achieving a current density of 10 mA cm-2 in aqueous solutions 1.0 M KOH, 0.5 M H2SO4, and 1.0 M phosphate-buffered saline (PBS), respectively, requires only an overpotential of 48, 62, and 164 mV. The Tafel slopes for each case are 43, 32, and 62 mV dec-1, respectively. In this study, the synergistic effect of MoS2 and CoS2 is conducive to electron transfer, making the MoS2@CoS2 heterojunction show excellent electrocatalytic performance. The synergistic effects arising from the heterojunction and sulfur vacancy not only contribute to the observed catalytic prowess but also provide a valuable model and reference for the exploration of other efficient electrocatalysts. This research marks a significant stride toward overcoming the challenges associated with developing electrocatalysts for practical hydrogen evolution applications.

The novel HLA-B*15:02:15 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*15:02:15 differs from HLA-B*15:02:01:01 by one nucleotide in exon 2.

Six-gene prognostic signature for non-alcoholic fatty liver disease susceptibility using machine learning.

BACKGROUND: nonalcoholic fatty liver disease (NAFLD) is a common liver disease affecting the global population and its impact on human health will continue to increase. Genetic susceptibility is an important factor influencing its onset and progression, and there is a lack of reliable methods to predict the susceptibility of normal populations to NAFLD using appropriate genes. METHODS: RNA sequencing data relating to nonalcoholic fatty liver disease was analyzed using the "limma" package within the R software. Differentially expressed genes were obtained through preliminary intersection screening. Core genes were analyzed and obtained by establishing and comparing 4 machine learning models, then a prediction model for NAFLD was constructed. The effectiveness of the model was then evaluated, and its applicability and reliability verified. Finally, we conducted further gene correlation analysis, analysis of biological function and analysis of immune infiltration. RESULTS: By comparing 4 machine learning algorithms, we identified SVM as the optimal model, with the first 6 genes (CD247, S100A9, CSF3R, DIP2C, OXCT 2 and PRAMEF16) as predictive genes. The nomogram was found to have good reliability and effectiveness. Six genes' receiver operating characteristic curves (ROC) suggest an essential role in NAFLD pathogenesis, and they exhibit a high predictive value. Further analysis of immunology demonstrated that these 6 genes were closely connected to various immune cells and pathways. CONCLUSION: This study has successfully constructed an advanced and reliable prediction model based on 6 diagnostic gene markers to predict the susceptibility of normal populations to NAFLD, while also providing insights for potential targeted therapies.