Dietary fiber alleviates alcoholic liver injury via Bacteroides acidifaciens and subsequent ammonia detoxification.

The gut microbiota and diet-induced changes in microbiome composition have been linked to various liver diseases, although the specific microbes and mechanisms remain understudied. Alcohol-related liver disease (ALD) is one such disease with limited therapeutic options due to its complex pathogenesis. We demonstrate that a diet rich in soluble dietary fiber increases the abundance of Bacteroides acidifaciens (B. acidifaciens) and alleviates alcohol-induced liver injury in mice. B. acidifaciens treatment alone ameliorates liver injury through a bile salt hydrolase that generates unconjugated bile acids to activate intestinal farnesoid X receptor (FXR) and its downstream target, fibroblast growth factor-15 (FGF15). FGF15 promotes hepatocyte expression of ornithine aminotransferase (OAT), which facilitates the metabolism of accumulated ornithine in the liver into glutamate, thereby providing sufficient glutamate for ammonia detoxification via the glutamine synthesis pathway. Collectively, these findings uncover a potential therapeutic strategy for ALD involving dietary fiber supplementation and B. acidifaciens.

Association between hemoglobin and non-alcoholic fatty liver disease (NAFLD) in United States adults: Results from NHANES 2017-2020.

Background: Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition of increasing prevalence, is closely related to various metabolic disorders. Hemoglobin, a protein that transports oxygen in red blood cells, is the focus of this study, which seeks to investigate its potential association with NAFLD. Methods: We selected 6,516 eligible adult participants from the United States using the 2017-2020 National Health and Nutrition Examination Survey database for cross-sectional analyses. We analyzed the association of hemoglobin with NAFLD using weighted logistic regression models. Results: The study performed a weighted logistic regression modeling analysis, which verified that hemoglobin levels were positively associated with NAFLD, especially in the higher hemoglobin quartile groups. Subgroup analyses revealed no significant interactions, demonstrating the robustness of the model. The analysis of mediation effects showed that Gamma-Glutamyl Transferase, Alanine Aminotransferase, and triglycerides were important mediating variables in the relationship between hemoglobin and NAFLD. Conclusion: Increased hemoglobin levels were found to be significantly and independently associated with an increased NAFLD risk. This insight is crucial for the risk assessment and early detection of NAFLD, underscoring the need for heightened vigilance in individuals with higher hemoglobin levels.

Bismuth Sulfide Nanoflowers Facilitated miR339 Delivery to Overcome Stemness and Radioresistance through Ubiquitin-Specific Peptidase 8 in Esophageal Cancer.

Despite the superior efficacy of radiotherapy in esophageal squamous cell carcinoma (ESCC), radioresistance by cancer stem cells (CSCs) leads to recurrence, metastasis, and treatment failure. Therefore, it is necessary to develop CSC-based therapies to enhance radiotherapy. miR-339-5p (miR339) is involved in stem cell division and DNA damage checkpoint signaling pathways based on ESCC cohort. miR339 inhibited ESCC cell stemness and enhanced radiation-induced DNA damage by targeting USP8, suggesting that it acts as a potential CSC regulator and radiosensitizer. Considering the limited circulating periods and poor tumor-targeting ability of miRNA, a multifunctional nanoplatform based on bismuth sulfide nanoflower (Bi@PP) is developed to efficiently deliver miR339 and improve radioresistance. Intriguingly, Bi@PP encapsulates more miR339 owing to their flower-shaped structure, delivering more than 1000-fold miR339 into cells, superior to free miR339 alone. Besides being used as a carrier, Bi@PP is advantageous for dynamically monitoring the distribution of delivered miR339 in vivo while simultaneously inhibiting tumor growth. Additionally, Bi@PP/miR339 can significantly enhance radiotherapy efficacy in patient-derived xenograft models. This multifunctional platform, incorporating higher miRNA loading capacity, pH responsiveness, hypoxia relief, and CT imaging, provides another method to promote radiosensitivity and optimize ESCC treatment.

Fat body-derived juvenile hormone acid methyltransferase functions to maintain iron homeostasis in Drosophila melanogaster.

Iron homeostasis is of critical importance to living organisms. Drosophila melanogaster has emerged as an excellent model to study iron homeostasis, while the regulatory mechanism of iron metabolism remains poorly understood. Herein, we accidently found that knockdown of juvenile hormone (JH) acid methyltransferase (Jhamt) specifically in the fat body, a key rate-limiting enzyme for JH synthesis, led to iron accumulation locally, resulting in serious loss and dysfunction of fat body. Jhamt knockdown-induced phenotypes were mitigated by iron deprivation, antioxidant and Ferrostatin-1, a well-known inhibitor of ferroptosis, suggesting ferroptosis was involved in Jhamt knockdown-induced defects in the fat body. Further study demonstrated that upregulation of Tsf1 and Malvolio (Mvl, homolog of mammalian DMT1), two iron importers, accounted for Jhamt knockdown-induced iron accumulation and dysfunction of the fat body. Mechanistically, Kr-h1, a key transcription factor of JH, acts downstream of Jhamt inhibiting Tsf1 and Mvl transcriptionally. In summary, the findings indicated that fat body-derived Jhamt is required for the development of Drosophila by maintaining iron homeostasis in the fat body, providing unique insight into the regulatory mechanisms of iron metabolism in Drosophila.

Comparison of CRISPR typing and conventional molecular methods for distinguishing Laribacter hongkongensis isolates from fish, frogs and humans.

High-resolution and efficient typing for Laribacter hongkongensis (L. hongkongensis) is essential for epidemiological investigation of such emerging foodborne pathogens. Clustered regularly interspaced short palindromic repeats (CRISPR) typing is an innovative molecular method that shows great promise for L. hongkongensis typing. Here, we explored the CRISPR typing method by combining CRISPR1 and CRISPR2 loci to characterize a collection of 109 L. hongkongensis isolates from humans and animals and compared it to current molecular methods such as pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The results showed that all three methods have high discriminatory power (diversity index was 0.9902 for PFGE, 0.9663 for CRISPR and 0.9562 for MLST); strong congruence was observed between them (Rand index was 0.969 between CRISPR and PFGE, 0.953 between CRISPR and MLST, 0.958 between PFGE and MLST). CRISPR typing could well distinguish the isolates in the same STs or PFGE profiles, and the genetic information contained by the CRISPR array is useful for deep phylogenetic typing. We demonstrate that rapid CRISPR typing is a practical genetic fingerprinting tool with high resolution, comparable ease of use and lower cost, ability to track the source of various groups of L. hongkongensis strains and indication of genetic characteristics.

Explainable coronary artery disease prediction model based on AutoGluon from AutoML framework.

Objective: This study focuses on the innovative application of Automated Machine Learning (AutoML) technology in cardiovascular medicine to construct an explainable Coronary Artery Disease (CAD) prediction model to support the clinical diagnosis of CAD. Methods: This study utilizes a combined data set of five public data sets related to CAD. An ensemble model is constructed using the AutoML open-source framework AutoGluon to evaluate the feasibility of AutoML in constructing a disease prediction model in cardiovascular medicine. The performance of the ensemble model is compared against individual baseline models. Finally, the disease prediction ensemble model is explained using SHapley Additive exPlanations (SHAP). Results: The experimental results show that the AutoGluon-based ensemble model performs better than the individual baseline models in predicting CAD. It achieved an accuracy of 0.9167 and an AUC of 0.9562 in 4-fold cross-bagging. SHAP measures the importance of each feature to the prediction of the model and explains the prediction results of the model. Conclusion: This study demonstrates the feasibility and efficacy of AutoML technology in cardiovascular medicine and highlights its potential in disease prediction. AutoML reduces the barriers to model building and significantly improves prediction accuracy. Additionally, the integration of SHAP enhances model transparency and explainability, which is critical to ensuring model credibility and widespread adoption in cardiovascular medicine.

[Research on intelligent tooth segmentation method combining multiple seed region growth and boundary extension].

The segmentation of dental models is a crucial step in computer-aided diagnosis and treatment systems for oral healthcare. To address the issues of poor universality and under-segmentation in tooth segmentation techniques, an intelligent tooth segmentation method combining multiple seed region growth and boundary extension is proposed. This method utilized the distribution characteristics of negative curvature meshes in teeth to obtain new seed points and effectively adapted to the structural differences between the top and sides of teeth through differential region growth. Additionally, the boundaries of the initial segmentation were extended based on geometric features, which was effectively compensated for under-segmentation issues in region growth. Ablation experiments and comparative experiments with current state-of-the-art algorithms demonstrated that the proposed method achieved better segmentation of crowded dental models and exhibited strong algorithm universality, thus possessing the capability to meet the practical segmentation needs in oral healthcare.

Attribution classification method of APT malware based on multi-feature fusion.

In recent years, with the development of the Internet, the attribution classification of APT malware remains an important issue in society. Existing methods have yet to consider the DLL link library and hidden file address during the execution process, and there are shortcomings in capturing the local and global correlation of event behaviors. Compared to the structural features of binary code, opcode features reflect the runtime instructions and do not consider the issue of multiple reuse of local operation behaviors within the same APT organization. Obfuscation techniques more easily influence attribution classification based on single features. To address the above issues, (1) an event behavior graph based on API instructions and related operations is constructed to capture the execution traces on the host using the GNNs model. (2) ImageCNTM captures the local spatial correlation and continuous long-term dependency of opcode images. (3) The word frequency and behavior features are concatenated and fused, proposing a multi-feature, multi-input deep learning model. We collected a publicly available dataset of APT malware to evaluate our method. The attribution classification results of the model based on a single feature reached 89.24% and 91.91%. Finally, compared to single-feature classifiers, the multi-feature fusion model achieves better classification performance.

Corrigendum to "MiR-423-5p is a novel endogenous control for the quantification of circulating miRNAs in human esophageal squamous cell carcinoma" [Heliyon Volume 9, Issue 4, April 2023, Article e14515].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e14515.].

Activation of nicotinic acetylcholine receptor α7 subunit limits Zika viral infection via promoting autophagy and ferroptosis.

Vagus nerve regulates viral infection and inflammation via the alpha 7 nicotinic acetylcholine receptor (α7 nAChR); however, the role of α7 nAChR in ZIKA virus (ZIKV) infection, which can cause severe neurological diseases such as microcephaly and Guillain-Barré syndrome, remains unknown. Here, we first examined the role of α7 nAChR in ZIKV infection in vitro. A broad effect of α7 nAChR activation was identified in limiting ZIKV infection in multiple cell lines. Combined with transcriptomics analysis, we further demonstrated that α7 nAChR activation promoted autophagy and ferroptosis pathways to limit cellular ZIKV viral loads. Additionally, activation of α7 nAChR prevented ZIKV-induced p62 nucleus accumulation, which mediated an enhanced autophagy pathway. By regulating proteasome complex and an E3 ligase NEDD4, activation of α7 nAChR resulted in increased amount of cellular p62, which further enhanced the ferroptosis pathway to reduce ZIKV infection. Moreover, utilizing in vivo neonatal mouse models, we showed that α7 nAChR is essential in controlling the disease severity of ZIKV infection. Taken together, our findings identify an α7 nAChR-mediated effect that critically contributes to limiting ZIKV infection, and α7 nAChR activation offers a novel strategy for combating ZIKV infection and its complications.

Overactivation of XBP1 in plasma cells implies worse survival through innate immunity in esophageal squamous cell carcinoma.

To maintain protein homeostasis, X-box binding protein 1 (XBP1) undergoes splicing following the activation of the unfolded protein response (UPR) in response to endoplasmic reticulum (ER) stress. Although targeting ER stress represents a promising therapeutic strategy, a comprehensive understanding of XBP1 at the cellular level and the link between XBP1 and the innate nervous system is lacking. Here, TCGA pancancer datasets from 33 cancer types, scRNA pancancer datasets from 454 patients and bulk RNA-seq datasets from 155 paired esophageal squamous cell carcinoma (ESCC) patients were analyzed. To cope with ER stress, plasma cells tend to activate XBP1 after undergoing bacterial infection and inflammatory signaling from the innate immune system. Patients with high XBP1 expression in their plasma cells have a higher tumor grade and worse survival. However, activation of the innate immune system with increased XBP1 expression in plasma cells correlates with an increased lymphocyte ratio, indicative of a more robust immune response. Moreover, XBP1 activation appears to initiate leukocyte migration at the transcriptional level. Our study revealed that the XBP1-induced UPR could mediate the crosstalk between optimal acquired humoral immune responses and innate immunity in ESCC.

3D printing of fish-scale derived hydroxyapatite/chitosan/PCL scaffold for bone tissue engineering.

In the field of bone tissue repair, the treatment of bone defects has always posed a significant challenge. In recent years, the advancement of bone tissue engineering and regenerative medicine has sparked great interest in the development of innovative bone grafting materials. In this study, a novel hydroxyapatite (HA) material was successfully prepared and comprehensively characterized. Antimicrobial experiments and biological evaluations were conducted to determine its efficacy. Based on the aforementioned research findings, 3D printing technology was employed to fabricate HA/chitosan (CS)/ polycaprolactone (PCL) scaffolds. The composition of the scaffold materials was confirmed through X-ray diffractometer (XRD) and Fourier Transform Infrared Spectroscopy (FT-IR) tests, while the influence of different HA ratios on the scaffold surface morphology was observed. Additionally, antimicrobial experiments demonstrated the favorable antimicrobial activity of the scaffolds containing 30%HA + 5%CS + PCL. Furthermore, the water contact angle measurements confirmed the superhydrophilicity of the scaffolds. Finally, the excellent bioactivity and ability to promote tissue regeneration of the scaffolds were further confirmed by in vitro and in vivo experiments. This study provides new options for future repair and regeneration of bone tissue and clinical applications.

Enhancer demethylation-regulated gene score identified molecular subtypes, inspiring immunotherapy or CDK4/6 inhibitor therapy in oesophageal squamous cell carcinoma.

BACKGROUND: The 5-year survival rate of oesophageal squamous cell carcinoma (ESCC) is approximately 20%. The prognosis and drug response exhibit substantial heterogeneity in ESCC, impeding progress in survival outcomes. Our goal is to identify a signature for tumour subtype classification, enabling precise clinical treatments. METHODS: Utilising pre-treatment multi-omics data from an ESCC dataset (n = 310), an enhancer methylation-eRNA-target gene regulation network was constructed and validated by in vitro experiments. Four machine learning methods collectively identified core target genes, establishing an Enhancer Demethylation-Regulated Gene Score (EDRGS) model for classification. The molecular function of EDRGS subtyping was explored in scRNA-seq (n = 60) and bulk-seq (n = 310), and the EDRGS's potential to predict treatment response was assessed in datasets of various cancer types. FINDINGS: EDRGS stratified ESCCs into EDRGS-high/low subtypes, with EDRGS-high signifying a less favourable prognosis in ESCC and nine additional cancer types. EDRGS-high exhibited an immune-hot but immune-suppressive phenotype with elevated immune checkpoint expression, increased T cell infiltration, and IFNγ signalling in ESCC, suggesting a better response to immunotherapy. Notably, EDRGS outperformed PD-L1 in predicting anti-PD-1/L1 therapy effectiveness in ESCC (n = 42), kidney renal clear cell carcinoma (KIRC, n = 181), and bladder urothelial carcinoma (BLCA, n = 348) cohorts. EDRGS-low showed a cell cycle-activated phenotype with higher CDK4 and/or CDK6 expression, demonstrating a superior response to the CDK4/6 inhibitor palbociclib, validated in ESCC (n = 26), melanoma (n = 18), prostate cancer (n = 15) cells, and PDX models derived from patients with pancreatic cancer (n = 30). INTERPRETATION: Identification of EDRGS subtypes enlightens ESCC categorisation, offering clinical insights for patient management in immunotherapy (anti-PD-1/L1) and CDK4/6 inhibitor therapy across cancer types. FUNDING: This study was supported by funding from the National Key R&D Program of China (2021YFC2501000, 2020YFA0803300), the National Natural Science Foundation of China (82030089, 82188102), the CAMS Innovation Fund for Medical Sciences (2021-I2M-1-018, 2022-I2M-2-001, 2021-I2M-1-067), the Fundamental Research Funds for the Central Universities (3332021091).

Final analysis of camrelizumab plus chemotherapy for untreated advanced or metastatic esophageal squamous cell carcinoma: The ESCORT-1st trial.

BACKGROUND: The interim analysis of the randomized phase 3 ESCORT-1st study demonstrated significantly longer overall survival (OS) and progression-free survival (PFS) for camrelizumab-chemotherapy than placebo-chemotherapy in untreated advanced/metastatic esophageal squamous cell carcinoma (ESCC). Here, we present the final analysis of this study and investigate potential indicators associated with OS. METHODS: Patients were randomized 1:1 to receive camrelizumab (200 mg) or placebo, both in combination with up to six cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were administered intravenously every 3 weeks. The co-primary endpoints were OS and PFS assessed by the independent review committee. FINDINGS: As of April 30, 2022, the median OS was significantly longer in the camrelizumab-chemotherapy group compared to the placebo-chemotherapy group (15.6 [95% confidence interval (CI): 14.0-18.4] vs. 12.6 months [95% CI 11.2-13.8]; hazard ratio [HR]: 0.70 [95% CI 0.58-0.84]; one-sided p < 0.0001), with 3-year OS rates of 25.6% and 12.8% in the two groups, respectively. The 2-year PFS rates were 20.4% in the camrelizumab-chemotherapy group and 3.4% in the placebo-chemotherapy group. Adverse events were consistent with those reported in the interim analysis. Higher PD-L1 expression correlated with extended OS, and multivariate analysis identified sex and prior history of radiotherapy as independent indicators of OS. CONCLUSIONS: The sustained and significant improvement in efficacy with camrelizumab-chemotherapy compared to placebo-chemotherapy, along with the absence of accumulating or delayed toxicities, supports the long-term use of camrelizumab-chemotherapy as a standard therapy in untreated advanced/metastatic ESCC. FUNDING: This study was funded by Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Immune-tumor interaction dictates spatially directed evolution of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a poor-prognostic cancer type with extensive intra- and inter-patient heterogeneity in both genomic variations and tumor microenvironment (TME). However, the patterns and drivers of spatial genomic and microenvironmental heterogeneity of ESCC remain largely unknown. Here, we generated a spatial multi-omic atlas by whole-exome, transcriptome, and methylome sequencing of 507 tumor samples from 103 patients. We identified a novel tumor suppressor PREX2, accounting for 22% of ESCCs with frequent somatic mutations or hyper-methylation, which promoted migration and invasion of ESCC cells in vitro. Analysis of the TME and quantification of subclonal expansion indicated that ESCCs undergo spatially directed evolution, where subclones mostly originated from the tumor center but had a biased clonal expansion to the upper direction of the esophagus. Interestingly, we found upper regions of ESCCs often underwent stronger immunoediting with increased selective fitness, suggesting more stringent immune selection. In addition, distinct TMEs were associated with variable genomic and clinical outcomes. Among them, hot TME was associated with high immune evasion and subclonal heterogeneity. We also found that immunoediting, instead of CD8+ T cell abundance, acts as an independent prognostic factor of ESCCs. Importantly, we found significant heterogeneity in previously considered potential therapeutic targets, as well as BRCAness characteristics in a subset of patients, emphasizing the importance of focusing on heterogeneity in ESCC targeted therapy. Collectively, these findings provide novel insights into the mechanisms of the spatial evolution of ESCC and inform precision therapeutic strategies.

Transforming Natural Eggshell and Diatomite into Bioactive Calcium Silicate Material for Bone Regeneration.

Calcium silicate (CS), a new and important bioceramic bone graft material, is prepared by using eggshells, which have a porous structure and are rich in calcium ions. Furthermore, the preparation of new CS materials using eggshells and diatomaceous earth minimizes their negative impact on the environment. In this study, we prepared CS materials using a high-temperature calcination method. The composition of the material was demonstrated by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analysis. Scanning electron microscopy (SEM) analysis confirmed the porous structure of the CS material. We also introduced ZnO to prepare ZnO-CS with antibacterial properties and showed that ZnO-CS exhibits excellent antibacterial effects through in vitro antibacterial experiments. Subsequent in vitro mineralization experiments demonstrated that ZnO-CS promoted the formation of a hydroxyapatite layer. Furthermore, in vitro cytotoxicity experiments demonstrated that ZnO-CS had very good biosafety and promoted cell proliferation. These findings were confirmed through subsequent cell proliferation experiments. Our results indicate that the novel ZnO-CS is a promising candidate for bone tissue engineering.

Woody encroachment induced earlier and extended growing season in boreal wetland ecosystems.

Woody plant encroachment (WPE), a widespread ecological phenomenon globally, has significant impacts on ecosystem structure and functions. However, little is known about how WPE affects phenology in wetland ecosystems of middle and high latitudes. Here, we investigated the regional-scale effects of WPE on the start (SOS), peak (POS), end (EOS), and length (GSL) of the growing season in boreal wetland ecosystems, and their underlying mechanisms, using remote sensing dataset during 2001-2016. Our results showed that WPE advanced the annual SOS and POS, while delaying EOS and extending GSL in boreal wetlands with these impacts increasing over time. When boreal wetland ecosystems were fully encroached by woody plants, the SOS and POS were advanced by 12.17 and 5.65 days, respectively, the EOS was postponed by 2.74 days, and the GSL was extended by 15.21 days. We also found that the impacts of WPE on wetland SOS were predominantly attributed to the increased degree of WPE (α), while climatic factors played a more significant role in controlling the POS and EOS responses to WPE. Climate change not only directly influenced phenological responses of wetlands to WPE but also exerted indirect effects by regulating soil moisture and α. Winter precipitation and spring temperature primarily determined the effects of WPE on SOS, while its impacts on POS were mainly controlled by winter precipitation, summer temperature, and precipitation, and the effects on EOS were mainly determined by winter precipitation, summer temperature, and autumn temperature. Our findings offer new insights into the understanding of the interaction between WPE and wetland ecosystems, emphasizing the significance of considering WPE effects to ensure accurate assessments of phenology changes.

Multimodal analysis of cfDNA methylomes for early detecting esophageal squamous cell carcinoma and precancerous lesions.

Detecting early-stage esophageal squamous cell carcinoma (ESCC) and precancerous lesions is critical for improving survival. Here, we conduct whole-genome bisulfite sequencing (WGBS) on 460 cfDNA samples from patients with non-metastatic ESCC or precancerous lesions and matched healthy controls. We develop an expanded multimodal analysis (EMMA) framework to simultaneously identify cfDNA methylation, copy number variants (CNVs), and fragmentation markers in cfDNA WGBS data. cfDNA methylation markers are the earliest and most sensitive, detectable in 70% of ESCCs and 50% of precancerous lesions, and associated with molecular subtypes and tumor microenvironments. CNVs and fragmentation features show high specificity but are linked to late-stage disease. EMMA significantly improves detection rates, increasing AUCs from 0.90 to 0.99, and detects 87% of ESCCs and 62% of precancerous lesions with >95% specificity in validation cohorts. Our findings demonstrate the potential of multimodal analysis of cfDNA methylome for early detection and monitoring of molecular characteristics in ESCC.

The intake of solid fat and cheese may be associated with a reduced risk of Helicobacter pylori infection status: a cross-sectional study based on NHANES 1999-2000.

BACKGROUND: Diet plays an important role in Helicobacter pylori (HP) infection, and our objective was to investigate potential connections between dietary patterns, specific food groups, and HP infection status in U.S. adults. METHODS: The data for this study was obtained from the NHANES (National Health and Nutrition Survey) database for the year 1999-2000. This cross-sectional study involved the selection of adults aged 20 years and older who had undergone dietary surveys and HP testing. Factor analysis was employed to identify dietary patterns, and logistic regression models were utilized to assess the association between these dietary patterns and specific food groups with HP infection status. RESULT: Based on the inclusion and exclusion criteria, our final analysis included 2,952 individuals. The median age of participants was 51.0 years, and 48.7% were male. In the study population, the overall prevalence of HP infection was 44.9%. Factor analysis revealed three distinct dietary patterns: High-fat and high-sugar pattern (including solid fats, refined grains, cheese, and added sugars); Vegetarian pattern (comprising fruits, juices, and whole grains); Healthy pattern (encompassing vegetables, nuts and seeds, and oils). Adjusted results showed that the high-fat and high-sugar pattern (OR = 0.689, 95% CI: 0.688-0.690), vegetarian pattern (OR = 0.802, 95% CI: 0.801-0.803), and healthy pattern (OR = 0.717, 95% CI: 0.716-0.718) were all linked to a lower likelihood of HP infection. Further analysis of the high-fat and high-sugar pattern revealed that solid fats (OR = 0.717, 95% CI: 0.716-0.718) and cheese (OR = 0.863, 95% CI: 0.862-0.864) were protective factors against HP infection, while refined grains (OR = 1.045, 95% CI: 1.044-1.046) and added sugars (OR = 1.014, 95% CI: 1.013-1.015) were identified as risk factors for HP infection. CONCLUSION: Both the Vegetarian pattern and the Healthy pattern are associated with a reduced risk of HP infection. Interestingly, the High-fat and High-sugar pattern, which is initially considered a risk factor for HP infection when the score is low, becomes a protective factor as the intake increases. Within this pattern, animal foods like solid fats and cheese play a protective role, while the consumption of refined grains and added sugars increases the likelihood of HP infection.

OTUB2 silencing promotes ovarian cancer via mitochondrial metabolic reprogramming and can be synthetically targeted by CA9 inhibition.

Ovarian cancer is an aggressive gynecological tumor characterized by a high relapse rate and chemoresistance. Ovarian cancer exhibits the cancer hallmark of elevated glycolysis, yet effective strategies targeting cancer cell metabolic reprogramming to overcome therapeutic resistance in ovarian cancer remain elusive. Here, we revealed that epigenetic silencing of Otubain 2 (OTUB2) is a driving force for mitochondrial metabolic reprogramming in ovarian cancer, which promotes tumorigenesis and chemoresistance. Mechanistically, OTUB2 silencing destabilizes sorting nexin 29 pseudogene 2 (SNX29P2), which subsequently prevents hypoxia-inducible factor-1 alpha (HIF-1α) from von Hippel-Lindau tumor suppressor-mediated degradation. Elevated HIF-1α activates the transcription of carbonic anhydrase 9 (CA9) and drives ovarian cancer progression and chemoresistance by promoting glycolysis. Importantly, pharmacological inhibition of CA9 substantially suppressed tumor growth and synergized with carboplatin in the treatment of OTUB2-silenced ovarian cancer. Thus, our study highlights the pivotal role of OTUB2/SNX29P2 in suppressing ovarian cancer development and proposes that targeting CA9-mediated glycolysis is an encouraging strategy for the treatment of ovarian cancer.