CHN nanocomposites and nanocoating resist enamel white spot lesions by enhancing remineralization and antibacterial activity.

Enamel white spot lesions (WSLs) are usually caused by the dissolution of minerals (mainly calcium and phosphate) on the tooth surface due to the acidic environment in the oral cavity. Without timely intervention, WSLs may lead to white spots or a sense of transparency on the tooth surface, and even the formation of dental caries (tooth decay) in severe cases. The key to preventing and treating WSLs is inhibiting the activity of acid-producing bacteria and promoting the remineralization of demineralized enamel. In this study, the network structure formed by sodium tripolyphosphate (TPP) cross-linked chitosan was used to stabilize calcium phosphate, and the multifunctional nanocomposite was constructed by integrating antibacterial components of traditional Chinese medicine, honokiol nanoparticles (HK-NPs) and sodium fluoride to achieve the purpose of resisting cariogenic bacteria and remineralizing with sustained release of calcium and phosphate ions. Notably, we enhanced the remineralization effect of nanocomposites with the help of functional nanocoatings inspired by the mussel biomimetic coating. The experimental results show that the synergistic remineralization effect of nanocomposite and nanocoating is better than that of a single strategy. This multi-prong treatment strategy provides the theoretical and experimental basis for the clinical prevention and treatment of WSLs.

Curcumin Inhibits α-Synuclein Aggregation by Acting on Liquid-Liquid Phase Transition.

Parkinson's disease (PD), the second most common neurodegenerative disorder, is linked to α-synuclein (α-Syn) aggregation. Despite no specific drug being available for its treatment, curcumin, from the spice turmeric, shows promise. However, its application in PD is limited by a lack of understanding of its anti-amyloidogenic mechanisms. In this study, we first reconstructed the liquid-liquid phase separation (LLPS) of α-Syn in vitro under different conditions, which may be an initial step in entraining the pathogenic aggregation. Subsequently, we evaluated the effects of curcumin on the formation of droplets, oligomers, and aggregated fibers during the LLPS of α-synuclein, as well as its impact on the toxicity of aggregated α-synuclein to cultured cells. Importantly, we found that curcumin can inhibit amyloid formation by inhibiting the occurrence of LLPS and the subsequent formation of oligomers of α-Syn in the early stages of aggregation. Finally, the molecular dynamic simulations of interactions between α-Syn decamer fibrils and curcumin showed that van der Waal's interactions make the largest contribution to the anti-aggregation effect of curcumin. These results may help to clarify the mechanism by which curcumin inhibits the formation of α-Syn aggregates during the development of PD.

A Machine learning model for predicting sepsis based on an optimized assay for microbial cell-free DNA sequencing.

OBJECTIVE: To integrate an enhanced molecular diagnostic technique to develop and validate a machine-learning model for diagnosing sepsis. METHODS: We prospectively enrolled patients suspected of sepsis from August 2021 to August 2023. Various feature selection algorithms and machine learning models were used to develop the model. The best classifier was selected using 5-fold cross validation set and then was applied to assess the performance of the model in the testing set. Additionally, we employed the Shapley Additive exPlanations (SHAP) method to illustrate the effects of the features. RESULTS: We established an optimized mNGS assay and proposed using the copies of microbe-specific cell-free DNA per milliliter of plasma (CPM) as the detection signal to evaluate the real burden, with strong precision and high accuracy. In total, 237 patients were eligible for participation, which were randomly assigned to either the training set (70 %, n = 165) or the testing set (30 %, n = 72). The random forest classifier achieved accuracy, AUC and F1 scores of 0.830, 0.918 and 0.856, respectively, outperforming other machine learning models in the training set. Our model demonstrated clinical interpretability and achieved good prediction performance in differentiating between bacterial sepsis and non-sepsis, with an AUC value of 0.85 and an average precision of 0.91 in the testing set. Based on the SHAP value, the top nine features of the model were PCT, CPM, CRP, ALB, SBPmin, RRmax, CREA, PLT and HRmax. CONCLUSION: We demonstrated the potential of machine-learning approaches for predicting bacterial sepsis based on optimized mcfDNA sequencing assay accurately.

2,2- dimethylbenzopyran derivatives containing pyridone structural fragments as selective dual-targeting inhibitors of HIF-1α and EZH2 for the treatment of lung cancer.

We formerly reported that EZH2 inhibitors sensitized HIF-1 inhibitor-resistant cells and inhibited HIF-1α to promote SUZ12 transcription, leading to enhanced EZH2 enzyme activity and elevated H3K27me3 levels, and conversely, inhibition of EZH2 promoted HIF-1α transcription. HIF-1α and EZH2 interacted to form a negative feedback loop that reinforced each other's activity. In this paper, a series of 2,2- dimethylbenzopyran derivatives containing pyridone structural fragments were designed and synthesized with DYB-03, a HIF-1α inhibitor previously reported by our group, and Tazemetostat, an EZH2 inhibitor approved by FDA, as lead compounds. Among these compounds, D-01 had significant inhibitory activities on HIF-1α and EZH2. In vitro experiments showed that D-01 significantly inhibited the migration of A549 cells, clone, invasion and angiogenesis. Moreover, D-01 had good pharmacokinetic profiles. All the results about compound D-01 could lay a foundation for the research and development of HIF-1α and EZH2 dual-targeting compounds.

Resting-state fMRI network efficiency as a mediator in the relationship between the glymphatic system and cognitive function in obstructive sleep apnea hypopnea syndrome: Insights from a DTI-ALPS investigation.

INTRODUCTION: Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with cognitive impairment and physiological complications, necessitating further understanding of its mechanisms. This study investigates the relationship between glymphatic system function, brain network efficiency, and cognitive impairment in OSAHS patients using diffusion tensor image analysis along the perivascular space (DTI-ALPS) and resting-state fMRI. MATERIALS AND METHODS: This study included 31 OSAHS patients and 34 age- and gender-matched healthy controls (HC). All participants underwent GE 3.0T magnetic resonance imaging (MRI) with diffusion tensor image (DTI) and resting-state fMRI scans. The DTI-ALPS index and brain functional networks were assessed. Differences between groups and correlations with clinical characteristics were analyzed. Additionally, the mediating role of brain network efficiency was explored. Finally, receiver operating characteristics (ROC) analysis assessed diagnostic performance. RESULTS: OSAHS patients had significantly lower ALPS-index (1.268 vs. 1.431, p < 0.0001) and moderate negative correlation with Apnea Hypopnea Index (AHI) (r = -0.389, p = 0.031), as well as moderate positive correlation with Montreal Cognitive Assessment (MoCA) (r = 0.525, p = 0.002). Moreover, global efficiency (Eg) of the brain network was positively correlated with the ALPS-index and MoCA scores in OSAHS patients (r = 0.405, p = 0.024; r = 0.56, p = 0.001, respectively). Furthermore, mediation analysis showed that global efficiency partially mediated the impact of glymphatic system dysfunction on cognitive impairment in OSAHS patients (indirect effect = 4.58, mediation effect = 26.9 %). The AUROC for identifying OSAHS and HC was 0.80 (95 % CI 0.69 to 0.91) using an ALPS-index cut-off of 1.35. CONCLUSIONS: OSAHS patients exhibit decreased ALPS-index, indicating impaired glymphatic system function. Dysfunction of the glymphatic system can affect cognitive function in OSAHS by disrupting brain functional network, suggesting a potential underlying pathological mechanism. Additionally, preliminary findings suggest that the ALPS-index may offer promise as a potential indicator for OSAHS.

Molecular characterization and functional analysis of Eimeria tenella ankyrin repeat-containing protein.

Chicken coccidiosis causes disastrous losses to the poultry industry all over the world. Eimeria tenella is the most prevalent of these disease-causing species. Our former RNA-seq indicated that E. tenella ankyrin repeat-containing protein (EtANK) was expressed differently between drug-sensitive (DS) and drug-resistant strains. In this study, we cloned EtANK and analyzed its translational and transcriptional levels using quantitative real-time PCR (qPCR) and western blotting. The data showed that EtANK was significantly upregulated in diclazuril-resistant (DZR) strain and maduramicin-resistant (MRR) strain compared with the drug-sensitive (DS) strain. In addition, the transcription levels in the DZR strains isolated from the field were higher than in the DS strain. The translation levels of EtANK were higher in unsporulated oocysts (UO) than in sporozoites (SZ), sporulated oocysts (SO), or second-generation merozoites (SM), and the protein levels in SM were significantly higher than in UO, SO, and SZ. The results of the indirect immunofluorescence localization showed that the protein was distributed mainly at the anterior region of SZ and on the surface and in the cytoplasm of SM. The fluorescence intensity increased further with its development in vitro. An anti-rEtANK polyclonal antibody inhibited the invasive ability of E. tenella in DF-1 cells. These results showed that EtANK may be related to host cell invasion, required for the parasite's growth in the host, and may be involved in the development of E. tenella resistance to some drugs.

Characterization of the prognostic, diagnostic, and immunological roles of DSCC1 and its genomic alteration and instability in human cancers.

DNA replication and sister chromatid cohesion 1 (DSCC1) exerts various functions including sister chromatid cohesion. DSCC1 overexpression plays an important role in cancer development, such as in colorectal, breast, and hepatocellular cancers. The specific role of DSCC1 in tumor progression remains largely unknown, necessitating a pan-cancer investigation to understand the potential function of DSCC1 in various cancers. In this study, we obtained data on physiological conditions, transcriptional expression, survival prognosis, genomic alteration, genomic instability, enriched pathways, immune infiltration, and immunotherapy from The Cancer Genome Atlas, The Genotype-Tissue Expression, cBioPortal, and other publicly available databases to systematically characterize the oncogenic and immunological roles of DSCC1 in 33 different cancers. We found that DSCC1 expression was upregulated at both mRNA and protein levels in various cancers. Additionally, DSCC1 expression was associated with higher tumor stage and grade in specific cancers. DSCC1 was a potential pan-cancer prognostic biomarker for its close association with patient prognosis and a diagnostic biomarker for its high predictive value in distinguishing tumor tissues from normal tissues. DSCC1 was universally amplified across different cancers and tightly associated with genomic instability. Moreover, DSCC1 had a close relationship with tumor immune cell infiltration; thus, it could be used as a potential biomarker for predicting the response and survival of patients with cancer who receive immune checkpoint blockade treatment. To sum up, our study revealed that DSCC1 is a promising target for tumor therapy.

Common structure of saccades and microsaccades in visual perception.

We obtain large amounts of external information through our eyes, a process often considered analogous to picture mapping onto a camera lens. However, our eyes are never as still as a camera lens, with saccades occurring between fixations and microsaccades occurring within a fixation. Although saccades are agreed to be functional for information sampling in visual perception, it remains unknown if microsaccades have a similar function when eye movement is restricted. Here, we demonstrated that saccades and microsaccades share common spatiotemporal structures in viewing visual objects. Twenty-seven adults viewed faces and houses in free-viewing and fixation-controlled conditions. Both saccades and microsaccades showed distinctive spatiotemporal patterns between face and house viewing that could be discriminated by pattern classifications. The classifications based on saccades and microsaccades could also be mutually generalized. Importantly, individuals who showed more distinctive saccadic patterns between faces and houses also showed more distinctive microsaccadic patterns. Moreover, saccades and microsaccades showed a higher structure similarity for face viewing than house viewing and a common orienting preference for the eye region over the mouth region. These findings suggested a common oculomotor program that is used to optimize information sampling during visual object perception.

Endometrial stem cells alleviate cisplatin-induced ferroptosis of granulosa cells by regulating Nrf2 expression.

BACKGROUND: Premature ovarian failure (POF) caused by cisplatin is a severe and intractable sequela for young women with cancer who received chemotherapy. Cisplatin causes the dysfunction of granulosa cells and mainly leads to but is not limited to its apoptosis and autophagy. Ferroptosis has been also reported to participate, while little is known about it. Our previous experiment has demonstrated that endometrial stem cells (EnSCs) can repair cisplatin-injured granulosa cells. However, it is still unclear whether EnSCs can play a repair role by acting on ferroptosis. METHODS: Western blotting and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were applied to detect the expression levels of ferroptosis-related genes. CCK-8 and 5-Ethynyl-2'-deoxyuridine (EdU) assays were used to evaluate cell viability. Transmission electron microscopy (TEM) was performed to detect ferroptosis in morphology. And the extent of ferroptosis was assessed by ROS, GPx, GSSG and MDA indicators. In vivo, ovarian morphology was presented by HE staining and the protein expression in ovarian tissue was detected by immunohistochemistry. RESULTS: Our results showed that ferroptosis could occur in cisplatin-injured granulosa cells. Ferroptosis inhibitor ferrostatin-1 (Fer-1) and EnSCs partly restored cell viability and mitigated the damage of cisplatin to granulosa cells by inhibiting ferroptosis. Moreover, the repair potential of EnSCs can be markedly blocked by ML385. CONCLUSION: Our study demonstrated that cisplatin could induce ferroptosis in granulosa cells, while EnSCs could inhibit ferroptosis and thus exert repair effects on the cisplatin-induced injury model both in vivo and in vitro. Meanwhile, Nrf2 was validated to participate in this regulatory process and played an essential role.

FGF2 promotes the proliferation of injured granulosa cells in premature ovarian failure via Hippo-YAP signaling pathway.

Young women undergoing anticancer treatment are at risk of premature ovarian failure (POF). Endometrial-derived stem cells (EnSCs) have demonstrated significant therapeutic potential for treating ovarian insufficiency, although the underlying mechanisms remain to be fully understood. This study aims to further investigate the therapeutic effects of EnSCs, particularly through the paracrine action of fibroblast growth factor 2 (FGF2), on POF. The findings show that exogenous FGF2 enhances the survival of ovarian granulosa cells damaged by cisplatin. FGF2 stimulates the proliferation of these damaged cells by suppressing the Hippo signaling pathway and activating YAP expression. In vivo experiments also revealed that FGF2 treatment significantly improves ovarian reserve and endocrine function in mice with POF. These results suggest that FGF2 can boost the proliferative capacity of damaged ovarian granulosa cells through the Hippo-YAP signaling pathway, providing a theoretical foundation for using EnSCs and FGF2 in clinical treatments for POF.

Glioma segmentation based on dense contrastive learning and multimodal features recalibration.

Accurate segmentation of different regions of gliomas from multimodal magnetic resonance (MR) images is crucial for glioma grading and precise diagnosis, but many existing segmentation methods are difficult to effectively utilize multimodal MR image information to recognize accurately the lesion regions with small size, low contrast and irregular shape. To address this issue, this work proposes a novel 3D glioma segmentation model DCL-MANet. DCL-MANet has an architecture of multiple encoders and one single decoder. Each encoder is used to extract MR image features of a given modality. To overcome the entangle problems of multimodal semantic features, a dense contrastive learning (DCL) strategy is presented to extract the modality-specific and common features. Following that, feature recalibration block (RFB) based on modality-wise attention is used to recalibrate the semantic features of each modality, enabling the model to focus on the features that are beneficial for glioma segmentation. These recalibrated features are input into the decoder to obtain the segmentation results. To verify the superiority of the proposed method, we compare it with several state-of-the-art (SOTA) methods in terms of Dice, average symmetric surface distance (ASSD), HD95 and volumetric similarity (Vs). The comparison results show that the average Dice, ASSD, HD95 and Vs of DCL-MANet on all tumor regions are improved at least by 0.66%, 3.47%, 8.94% and 1.07% respectively. For small enhance tumor (ET) region, the corresponding improvement can be up to 0.37%, 7.83%, 11.32%, and 1.35%, respectively. In addition, the ablation results demonstrate the effectiveness of the proposed DCL and RFB, and combining them can significantly increase Dice (1.59%) and Vs (1.54%) while decreasing ASSD (40.51%) and HD95 (45.16%) on ET region. The proposed DCL-MANet could disentangle multimodal features and enhance the semantics of modality-dependent features, providing a potential means to accurately segment small lesion regions in gliomas.

Industrial Metaverse for Smart Manufacturing: Model, Architecture, and Applications.

Smart manufacturing has been transforming toward industrial digitalization integrated with various advanced technologies. Metaverse has been evolving as a next-generation paradigm of a digital space extended and augmented by reality. In the metaverse, users are interconnected for various virtual activities. In consideration of advanced possibilities that may be brought by the metaverse, it is envisioned that industrial metaverse should be integrated into smart manufacturing to upgrade industry for more visible, intelligent and efficient production in the future. Therefore, a conceptual model, named IMverse Model, and novel characteristics of the industrial metaverse for smart manufacturing are proposed in this article. Besides, an industrial metaverse architecture, named IMverse Architecture, is proposed involving several key enabling technologies. Typical innovative applications of the industrial metaverse throughout the whole product life cycle for smart manufacturing are presented with insights. Nonetheless, in prospect of future, the industrial metaverse still faces limitations and is far from implementation. Thus, challenges and open issues of the industrial metaverse for smart manufacturing are discussed, then outlook is provided for further research and application.

Mono-UFMylation promotes misfolding-associated secretion of α-synuclein.

Stressed cells secret misfolded proteins lacking signaling sequence via an unconventional protein secretion (UcPS) pathway, but how misfolded proteins are targeted selectively in UcPS is unclear. Here, we report that misfolded UcPS clients are subject to modification by a ubiquitin-like protein named ubiquitin-fold modifier 1 (UFM1). Using α-synuclein (α-Syn) as a UcPS model, we show that mutating the UFMylation sites in α-Syn or genetic inhibition of the UFMylation system mitigates α-Syn secretion, whereas overexpression of UFBP1, a component of the endoplasmic reticulum-associated UFMylation ligase complex, augments α-Syn secretion in mammalian cells and in model organisms. UFM1 itself is cosecreted with α-Syn, and the serum UFM1 level correlates with that of α-Syn. Because UFM1 can be directly recognized by ubiquitin specific peptidase 19 (USP19), a previously established UcPS stimulator known to associate with several chaperoning activities, UFMylation might facilitate substrate engagement by USP19, allowing stringent and regulated selection of misfolded proteins for secretion and proteotoxic stress alleviation.

Dynamic projection mapping for non-planar objects with a variable focus lens and visual feedback.

Dynamic projection mapping for moving objects has attracted much attention in recent years. However, conventional approaches have faced some issues, such as the target objects being limited to the moving speed of the objects, the limitation of the narrow depth-of-field optics, and the planar shape objects. This work proposed an adaptive three-dimensional projection prototype, and it could project an always in-focus image on a non-planar object based on liquid lens optics. The location of the non-planar object could be detected, and the mapped projection contents calculated; as a result, a stable "printed" projection mapping should be viewed on a moving object.

Vasorin exocytosed from glioma cells facilitates angiogenesis via VEGFR2/AKT signaling pathway.

Glioma is a highly vascularized tumor of the central nervous system. Angiogenesis plays a predominant role in glioma progression and is considered an important therapeutic target. Our previous study showed that vasorin (VASN), a transmembrane protein, is overexpressed in glioma and promotes angiogenesis; however, the potential mechanism remains unclear. In this study, we found that human vascular endothelial cells (hECs) co-cultured with VASN-overexpressing glioma cells exhibited accelerated migration ability and increased expression of VASN originated from glioma cells. VASN was found in exosomes secreted by glioma cells and could be taken up by hECs. hECs showed more edge filopodia and significantly upregulated expression of endothelial tip cell marker gene and protein levels after co-culture with VASN-overexpressing glioma cells. In clinical glioma tissue and orthotopic transplantation glioma tissue, the vascular density and the number of vascular endothelial cells with a tip cell phenotype in VASN-overexpressed tissues were significantly higher than in tissues with low expression. At the molecular level, VASN interacted with VEGFR2 and caused internalization and autophosphorylation of VEGFR2 protein, and then activated the AKT signaling pathway. Our study collectively reveals the function and mechanism of VASN in facilitating angiogenesis in glioma, providing a new therapeutic target for glioma. Implications: These findings demonstrate that VASN exocytosed from glioma cells enhanced the migration of vascular endothelial cells by VEGFR2/AKT signaling pathway.

Direct Observation of Z-Scheme Route in Cu31 S16 /Znx Cd1-x S Heteronanoplates for Highly Efficient Photocatalytic Hydrogen Evolution.

Although photocatalytic hydrogen production from water holds great potential as a renewable and sustainable energy alternative, the practical application of the technology demands cost-effective, simple photocatalytic systems with high efficiency in hydrogen evolution reaction (HER). Herein, the synthesis and characterization of Cu31 S16 /Znx Cd1-x S heterostructured nanoplates (Cu31 S16 /ZnCdS HNPs) as a high photocatalytic system are reported. The cost-effective, hierarchical structures are easily prepared using the Cu31 S16 NPs as the seed by the epitaxial growth of the ZnCdS nanocrystals (NCs). The Cu31 S16 /ZnCdS without the noble metal cocatalyst exhibits a high HER rate of 61.7 mmol g-1  h-1 , which is 8,014 and 17 times higher than that of Cu31 S16 and ZnCdS, respectively, under visible light irradiation. The apparent quantum yield (AQY) of Cu31 S16 /ZnCdS reaches 67.9% at 400 nm with the highest value so far in the reported ZnCdS-based photocatalysts. The excellent activity and stability of the Cu31 S16 /ZnCdS are attributed to the formation of a strong internal electric field (IEF) and the Z-scheme pathway. The comprehensive experiments and theoretical calculations provide the direct evidences of the Z-scheme route. This work may offer a way for the design and development of efficient photocatalysts to achieve solar-to-chemical energy conversion at a practically useful level.

The regulatory relationship between NAMPT and PD-L1 in cancer and identification of a dual-targeting inhibitor.

Cancer is a heterogeneous disease. Although both tumor metabolism and tumor immune microenvironment are recognized as driving factors in tumorigenesis, the relationship between them is still not well-known, and potential combined targeting approaches remain to be identified. Here, we demonstrated a negative correlation between the expression of NAMPT, an NAD+ metabolism enzyme, and PD-L1 expression in various cancer cell lines. A clinical study showed that a NAMPTHigh PD-L1Low expression pattern predicts poor prognosis in patients with various cancers. In addition, pharmacological inhibition of NAMPT results in the transcription upregulation of PD-L1 by SIRT-mediated acetylation change of NF-κB p65, and blocking PD-L1 would induce NAMPT expression through a HIF-1-dependent glycolysis pathway. Based on these findings, we designed and synthesized a dual NAMPT/PD-L1 targeting compound, LZFPN-90, which inhibits cell growth in a NAMPT-dependent manner and blocks the cell cycle, subsequently inducing apoptosis. Under co-culture conditions, LZFPN-90 treatment contributes to the proliferation and activation of T cells and blocks the growth of cancer cells. Using mice bearing genetically manipulated tumors, we confirmed that LZFPN-90 exerted target-dependent antitumor activities, affecting metabolic processes and the immune system. In conclusion, our results demonstrate the relevance of NAD+-related metabolic processes in antitumor immunity and suggest that co-targeting NAD+ metabolism and PD-L1 represents a promising therapeutic approach.

Unveiling potential drug targets for hyperparathyroidism through genetic insights via Mendelian randomization and colocalization analyses.

Hyperparathyroidism (HPT) manifests as a complex condition with a substantial disease burden. While advances have been made in surgical interventions and non-surgical pharmacotherapy for the management of hyperparathyroidism, radical options to halt underlying disease progression remain lacking. Identifying putative genetic drivers and exploring novel drug targets that can impede HPT progression remain critical unmet needs. A Mendelian randomization (MR) analysis was performed to uncover putative therapeutic targets implicated in hyperparathyroidism pathology. Cis-expression quantitative trait loci (cis-eQTL) data serving as genetic instrumental variables were obtained from the eQTLGen Consortium and Genotype-Tissue Expression (GTEx) portal. Hyperparathyroidism summary statistics for single nucleotide polymorphism (SNP) associations were sourced from the FinnGen study (5590 cases; 361,988 controls). Colocalization analysis was performed to determine the probability of shared causal variants underlying SNP-hyperparathyroidism and SNP-eQTL links. Five drug targets (CMKLR1, FSTL1, IGSF11, PIK3C3 and SLC40A1) showed significant causation with hyperparathyroidism in both eQTLGen and GTEx cohorts by MR analysis. Specifically, phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) and solute carrier family 40 member 1 (SLC40A1) showed strong evidence of colocalization with HPT. Multivariable MR and Phenome-Wide Association Study analyses indicated these two targets were not associated with other traits. Additionally, drug prediction analysis implies the potential of these two targets for future clinical applications. This study identifies PIK3C3 and SLC40A1 as potential genetically proxied druggable genes and promising therapeutic targets for hyperparathyroidism. Targeting PIK3C3 and SLC40A1 may offer effective novel pharmacotherapies for impeding hyperparathyroidism progression and reducing disease risk. These findings provide preliminary genetic insight into underlying drivers amenable to therapeutic manipulation, though further investigation is imperative to validate translational potential from preclinical models through clinical applications.

Immunoglobulin G-mediated food intolerance and metabolic syndrome influence the occurrence of reflux esophagitis in Helicobacter pylori-infected patients.

BACKGROUND: Reflux esophagitis has an increasing prevalence and complex and diverse symptoms. Identifying its risk factors is crucial to understanding the etiology, prevention, and management of the disease. The occurrence of reflux esophagitis may be associated with food reactions, Helicobacter pylori (H. pylori) infection, and metabolic syndromes. AIM: To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin (Ig) G-mediated food intolerance, H. pylori infection, and metabolic syndrome on reflux esophagitis. METHODS: Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively enrolled. The patients' basic information, test results, gastroscopy results, H. pylori test results, and IgG-mediated food intolerance results were collected. Multivariate logistic regression analysis was used to analyze risk factors for reflux esophagitis. Statistical mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on H. pylori infection affecting reflux esophagitis. RESULTS: A total of 7954 outpatients were included; the prevalence of reflux esophagitis, IgG-mediated food intolerance, H. pylori infection, and metabolic syndrome were 20.84%, 61.77%, 35.91%, and 60.15%, respectively. Multivariate analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance (OR = 1.688, 95%CI: 1.497-1.903, P < 0.00001) and metabolic syndrome (OR = 1.165, 95%CI: 1.030-1.317, P = 0.01484), and the independent protective factor for reflux esophagitis was H. pylori infection (OR = 0.400, 95%CI: 0.351-0.456, P < 0.00001). IgG-mediated food intolerance had a partially positive mediating effect on H. pylori infection as it was associated with reduced occurrence of reflux esophagitis (P = 0.0200). Metabolic syndrome had a partially negative mediating effect on H. pylori infection and reduced the occurrence of reflux esophagitis (P = 0.0220). CONCLUSION: Patients with IgG-mediated food intolerance and metabolic syndrome were at higher risk of developing reflux esophagitis, while patients with H. pylori infection were at lower risk. IgG-mediated food intolerance reduced the risk of reflux esophagitis pathogenesis in patients with H. pylori infection; however, metabolic syndrome increased the risk of patients with H. pylori infection developing reflux esophagitis.