Comprehensive analysis of the function of helicobacter-associated ferroptosis gene YWHAE in gastric cancer through multi-omics integration, molecular docking, and machine learning.

Gastric cancer is strongly associated with Helicobacter pylori (H. pylori) infection. However, the molecular mechanisms underlying the development of gastric cancer in the context of H. pylori infection, particularly in relation to ferroptosis, remain poorly understood. In this study, we investigated the role of the Helicobacter-associated ferroptosis gene YWHAE in gastric cancer. We analyzed multi-omics data, performed molecular docking, and employed machine learning to comprehensively evaluate the expression, function, and potential implications in gastric cancer, including its influence on drug sensitivity, mutation, immune microenvironment, immunotherapy, and prognosis. Our findings demonstrated that the YWHAE gene exhibits high expression in both H. pylori-associated gastritis and gastric cancer. Pan-cancer analysis revealed elevated expression of YWHAE in several cancer types compared to normal tissues. We also examined the methylation, single nucleotide variations (SNVs), and copy number variations (CNVs) associated with YWHAE. Single-cell analysis indicated that the YWHAE gene is expressed in various cell types, with its expression level potentially influenced by H. pylori infection. Functionally, we observed a positive correlation between YWHAE gene expression and ferroptosis in gastric cancer and associated with multiple cancer-related signaling pathways, including MAPK, NF-κB, and PI3K. Furthermore, we predicted five small molecule compounds that show promise for treating gastric cancer patients and screened five drugs with the highest correlation with YWHAE and validated them by molecular docking. Additionally, significant differences were observed in various immune cell types and immunotherapeutic response between the high and low YWHAE gene expression groups. Moreover, we found a positive correlation between YWHAE gene expression and the tumour mutation burden (TMB). By applying 10 machine learning algorithms and 101 integration combinations, we developed a prognostic model for YWHAE-related genes. Finally, qRT-PCR and immunohistochemistry (IHC) consistently demonstrated the upregulation of YWHAE in gastric cancer. In conclusion, we conducted a comprehensive analysis of YWHAE gene in gastric cancer. Our findings provided novel insights into the role of YWHAE as a gene associated with H. pylori infection and ferroptosis in gastric cancer and expanded our understanding of the molecular mechanisms underlying gastric carcinogenesis.

Dissecting the genetic basis of heterosis in elite super-hybrid rice.

Y900 is one of the top hybrid rice (Oryza sativa) varieties, with its yield exceeding 15 t·hm-2. To dissect the mechanism of heterosis, we sequenced the male parent line R900 and female parent line Y58S using long-read and Hi-C technology. High-quality reference genomes of 396.41 Mb and 398.24 Mb were obtained for R900 and Y58S, respectively. Genome-wide variations between the parents were systematically identified, including 1,367,758 single-nucleotide polymorphisms, 299,149 insertions/deletions, and 4,757 structural variations. The level of variation between Y58S and R900 was the lowest among the comparisons of Y58S with other rice genomes. More than 75% of genes exhibited variation between the two parents. Compared with other two-line hybrids sharing the same female parent, the portion of Geng/japonica (GJ)-type genetic components from different male parents increased with yield increasing in their corresponding hybrids. Transcriptome analysis revealed that the partial dominance effect was the main genetic effect that constituted the heterosis of Y900. In the hybrid, both alleles from the two parents were expressed, and their expression patterns were dynamically regulated in different tissues. The cis-regulation was dominant for young panicle tissues, while trans-regulation was more common in leaf tissues. Overdominance was surprisingly prevalent in stems and more likely regulated by the trans-regulation mechanism. Additionally, R900 contained many excellent GJ haplotypes, such as NARROW LEAF1, Oryza sativa SQUAMOSA PROMOTER BINDING PROTEIN-LIKE13, and Grain number, plant height, and heading date8, making it a good complement to Y58S. The fine-tuned mechanism of heterosis involves genome-wide variation, GJ introgression, key functional genes, and dynamic gene/allele expression and regulation pattern changes in different tissues and growth stages.

Treatment failure is a key factor in the development of Helicobacter pylori resistance.

BACKGROUND: Helicobacter pylori eradication failure influences its antibiotic resistance. AIMS: This study aimed to evaluate the effect of previous treatment failures on it, including the changes in the antibiotic resistance rates, minimal inhibitory concentration (MIC) distributions, and resistance patterns. MATERIALS AND METHODS: This single-center retrospective study included 860 primary isolates and 247 secondary isolates. Antibiotic susceptibility testing was performed for amoxicillin, metronidazole, clarithromycin, levofloxacin, furazolidone, tetracycline, and rifampicin. The demographic data and detailed regimens were collected. RESULTS: The primary resistance rates to amoxicillin, metronidazole, clarithromycin, levofloxacin, tetracycline, rifampin, and furazolidone were 5.93%, 83.84%, 28.82%, 26.28%, 0.35%, 1.16%, and 0%, while secondary were 25.10%, 92.31%, 79.76%, 63.16%, 1.06%, 3.19%, and 0%, respectively. The resistance rates to amoxicillin, metronidazole, clarithromycin, and levofloxacin increased significantly with the number of treatment failures accumulated, and showed a linear trend. The proportion of primary and secondary multidrug-resistant (MDR) isolates were 17.79% and 63.16%, respectively. The MIC values of amoxicillin, clarithromycin, and levofloxacin were elevated significantly with medication courses increased. CONCLUSION: The prevalence of amoxicillin, clarithromycin, levofloxacin, and metronidazole resistance would increase rapidly following first-line treatment failure, as well as the MIC values of them. Clinicians should pay great attention to the first-line treatment to cure H. pylori infection successfully.

Impact of Helicobacter pylori colonization density and depth on gastritis severity.

BACKGROUND AND OBJECTIVES: Helicobacter pylori (H. pylori) infection is the most common etiology of chronic gastric. H. pylori gastritis would gradually evolve into gastric atrophy, intestinal metaplasia, dysplasia and malignant lesions. Herein, this study aimed to investigate the potential impact of H. pylori colonization density and depth on the severity of histological parameters of gastritis. METHODS: A prospective monocentric study was conducted from December 2019 to July 2022, enrolling patients with confirmed chronic H. pylori infection via histopathological evaluation. H. pylori colonization status was detected by immunohistochemical staining, pathological changes of gastric specimens were detected by hematoxylin eosin staining. Epidemiological, endoscopic and histopathological data were collected. RESULTS: A total of 1120 patients with a mean age of 45.8 years were included. Regardless of the previous history of H. pylori eradication treatment, significant correlations were observed between the density and depth of H. pylori colonization and the intensity of gastritis activity (all P < 0.05). Patients with the lowest level of H. pylori colonization density and depth exhibited the highest level of mild activity. In whole participants and anti-H. pylori treatment-naive participants, H. pylori colonization density and depth were markedly correlated with the severity of chronic gastritis and gastric atrophy (all P < 0.05). H. pylori colonization density (P = 0.001) and depth (P = 0.047) were significantly associated with ulcer formation in patients naive to any anti-H. pylori treatment. No significant associations were observed between the density and depth of H. pylori colonization and other histopathological findings including lymphadenia, lymphoid follicle formation and dysplasia. CONCLUSIONS: As the density and depth of H. pylori colonization increased, so did the activity and severity of gastritis, along with an elevated risk of ulcer formation.

mmSafe: A Voice Security Verification System Based on Millimeter-Wave Radar.

With the increasing popularity of smart devices, users can control their mobile phones, TVs, cars, and smart furniture by using voice assistants, but voice assistants are susceptible to intrusion by outsider speakers or playback attacks. In order to address this security issue, a millimeter-wave radar-based voice security authentication system is proposed in this paper. First, the speaker's fine-grained vocal cord vibration signal is extracted by eliminating static object clutter and motion effects; second, the weighted Mel Frequency Cepstrum Coefficients (MFCCs) are obtained as biometric features; and finally, text-independent security authentication is performed by the WMHS (Weighted MFCCs and Hog-based SVM) method. This system is highly adaptable and can authenticate designated speakers, resist intrusion by other unspecified speakers as well as playback attacks, and is secure for smart devices. Extensive experiments have verified that the system achieves a 93.4% speaker verification accuracy and a 5.8% miss detection rate for playback attacks.

Millimeter wave gesture recognition using multi-feature fusion models in complex scenes.

As a form of body language, the gesture plays an important role in smart homes, game interactions, and sign language communication, etc. The gesture recognition methods have been carried out extensively. The existing methods have inherent limitations regarding user experience, visual environment, and recognition granularity. Millimeter wave radar provides an effective method for the problems lie ahead gesture recognition because of the advantage of considerable bandwidth and high precision perception. Interfering factors and the complexity of the model raise an enormous challenge to the practical application of gesture recognition methods as the millimeter wave radar is applied to complex scenes. Based on multi-feature fusion, a gesture recognition method for complex scenes is proposed in this work. We collected data in variety places to improve sample reliability, filtered clutters to improve the signal's signal-to-noise ratio (SNR), and then obtained multi features involves range-time map (RTM), Doppler-time map (DTM) and angle-time map (ATM) and fused them to enhance the richness and expression ability of the features. A lightweight neural network model multi-CNN-LSTM is designed to gestures recognition. This model consists of three convolutional neural network (CNN) for three obtained features and one long short-term memory (LSTM) for temporal features. We analyzed the performance and complexity of the model and verified the effectiveness of feature extraction. Numerous experiments have shown that this method has generalization ability, adaptability, and high robustness in complex scenarios. The recognition accuracy of 14 experimental gestures reached 97.28%.

Macrophage Tim-3 maintains intestinal homeostasis in DSS-induced colitis by suppressing neutrophil necroptosis.

T-cell immunoglobulin domain and mucin domain-3 (Tim-3) is a versatile immunomodulator that protects against intestinal inflammation. Necroptosis is a type of cell death that regulates intestinal homeostasis and inflammation. The mechanism(s) underlying the protective role of macrophage Tim-3 in intestinal inflammation is unclear; thus, we investigated whether specific Tim-3 knockdown in macrophages drives intestinal inflammation via necroptosis. Tim-3 protein and mRNA expression were assessed via double immunofluorescence staining and single-cell RNA sequencing (sc-RNA seq), respectively, in the colonic tissues of patients with inflammatory bowel disease (IBD) and healthy controls. Macrophage-specific Tim3-knockout (Tim-3M-KO) mice were generated to explore the function and mechanism of Tim-3 in dextran sodium sulfate (DSS)-induced colitis. Necroptosis was blocked by pharmacological inhibitors of receptor-interacting protein kinase (RIP)1, RIP3, and reactive oxygen species (ROS). Additionally, in vitro experiments were performed to assess the mechanisms of neutrophil necroptosis induced by Tim-3 knockdown macrophages. Although Tim-3 is relatively inactive in macrophages during colon homeostasis, it is highly active during colitis. Compared to those in controls, Tim-3M-KO mice showed increased susceptibility to colitis, higher colitis scores, and increased pro-inflammatory mediator expression. Following the administration of RIP1/RIP3 or ROS inhibitors, a significant reduction in intestinal inflammation symptoms was observed in DSS-treated Tim-3M-KO mice. Further analysis indicated the TLR4/NF-κB pathway in Tim-3 knockdown macrophages mediates the TNF-α-induced necroptosis pathway in neutrophils. Macrophage Tim-3 regulates neutrophil necroptosis via intracellular ROS signaling. Tim-3 knockdown macrophages can recruit neutrophils and induce neutrophil necroptosis, thereby damaging the intestinal mucosal barrier and triggering a vicious cycle in the development of colitis. Our results demonstrate a protective role of macrophage Tim-3 in maintaining gut homeostasis by inhibiting neutrophil necroptosis and provide novel insights into the pathogenesis of IBD.

Iatrogenic factors of Helicobacter pylori eradication failure: lessons from the frontline.

BACKGROUND: Iatrogenic factors play an important role in H. pylori eradication failure, whereas it can be easily missed. Therefore, we aimed to investigate and analyze these related iatrogenic factors of H. pylori eradication failure. METHODS: A total of 508 patients who experienced H. pylori eradication failure were included in this study conducted from December 2019 to February 2022. All the patients filled out a questionnaire including demographic characteristics, duration of treatment, regimens, dosage, and time intervals in rescue treatment. RESULTS: In the first-line treatment, 89 patients (17.5%, 89/508) used at least one antibiotic with high resistance rate in triple therapy and 57 patients (11.2%, 57/508) used two antibiotics with high resistance rates or other not recommended antibiotics in quadruple therapy. In the rescue therapy, 85 regimens were repeatedly used as salvage regimens in 58 patients (22.6%, 58/257) and 178 regimens containing antibiotics with high resistance rates were repeatedly used in 85 patients (33.1%, 85/257). CONCLUSION: To decrease the risk of H. pylori eradication failure, iatrogenic factors need to gain more attention. Clinicians should enhance their education and training to standardize the treatment regimens, better manage the H. pylori infection, and improve the eradication rate eventually.

Knowledge landscape of tumor-associated macrophage research: A bibliometric and visual analysis.

Background and aims: Tumor-associated macrophage (TAM) is a highly abundant immune population in tumor microenvironment, which plays an important role in tumor growth and progression. The aim of our study was to explore the development trends and research hotspots of TAM by bibliometric method. Methods: The publications related to TAM were obtained from the Web of Science Core Collection database. Bibliometric analysis and visualization were conducted using VOSviewer, CiteSpace and R software. Results: A total of 6,405 articles published between 2001 and 2021 were included. The United States and China received the most citations, whereas the University of Milan, the university of California San Francisco and Sun Yat-sen University were the main research institutions. Mantovani, Alberto from Humanitas University was the most productive authors with the most citations. Cancer Research published the most articles and received the most co-citations. Activation, angiogenesis, breast cancer, NF-κB and endothelial growth factor were important keywords in TAM research. Among them, PD-1/L1, nanoparticle, PI3Kγ, resistance and immune microenvironment have become the focus of attention in more recent research. Conclusions: The research on TAM is rapidly evolving with active cooperation worldwide. Anticancer therapy targeting TAM is emerging and promising area of future research, especially in translational application. This may provide guidance and new insights for further research in the field of TAM.

Elucidating colony bloom formation mechanism of a harmful alga Phaeocystis globosa (Prymnesiophyceae) using metaproteomics.

Phaeocystis is a globally distributed Prymnesiophyte genus and usually forms massive harmful colony blooms, which impact marine ecosystem, mariculture, human health, and even threaten coastal nuclear power plant safety. However, the mechanisms behind the colony formation from the solitary cells remain poorly understood. Here, we investigated metabolic processes of both solitary and non-flagellated colonial cells of Phaeocystis globosa at different colony bloom stages in the subtropical Beibu Gulf using a metaproteomic approach. Temperature was significantly correlated with Phaeocystis colony bloom formation, and the flagellated motile solitary cells with abundant flagellum-associated proteins, such as tubulin and dynein, were the exclusive cellular morphotype at the solitary cell stage featured with temperatures ≥21 °C. When the temperature decreased to <21 °C, tiny colonies appeared and the flagellum-associated proteins were down-regulated in both solitary and non-flagellated colonial cells, while proteins involved in biosynthesis, chain polymerization and aggregation of glycosaminoglycan (GAG), a key constituent of gelatinous matrix, were up-regulated, indicating the central role of active GAG biosynthesis during the colony formation. Furthermore, light utilization, carbon fixation, nitrogen assimilation, and amino acid and protein synthesis were also enhanced to provide sufficient energy and substrates for GAG biosynthesis. This study highlighted that temperature induced re-allocation of energy and substances toward GAG biosynthesis is essential for colony bloom formation of P. globosa.

Identification of a glycolysis- and lactate-related gene signature for predicting prognosis, immune microenvironment, and drug candidates in colon adenocarcinoma.

Background: Colon adenocarcinoma (COAD), a malignant gastrointestinal tumor, has the characteristics of high mortality and poor prognosis. Even in the presence of oxygen, the Warburg effect, a major metabolic hallmark of almost all cancer cells, is characterized by increased glycolysis and lactate fermentation, which supports biosynthesis and provides energy to sustain tumor cell growth and proliferation. However, a thorough investigation into glycolysis- and lactate-related genes and their association with COAD prognosis, immune cell infiltration, and drug candidates is currently lacking. Methods: COAD patient data and glycolysis- and lactate-related genes were retrieved from The Cancer Genome Atlas (TCGA) and Gene Set Enrichment Analysis (GSEA) databases, respectively. After univariate Cox regression analysis, a nonnegative matrix factorization (NMF) algorithm was used to identify glycolysis- and lactate-related molecular subtypes. Least absolute shrinkage and selection operator (LASSO) Cox regression identified twelve glycolysis- and lactate-related genes (ADTRP, ALDOB, APOBEC1, ASCL2, CEACAM7, CLCA1, CTXN1, FLNA, NAT2, OLFM4, PTPRU, and SNCG) related to prognosis. The median risk score was employed to separate patients into high- and low-risk groups. The prognostic efficacy of the glycolysis- and lactate-related gene signature was assessed using Kaplan-Meier (KM) survival and receiver operating characteristic (ROC) curve analyses. The nomogram, calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC) were employed to improve the clinical applicability of the prognostic signature. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on differentially expressed genes (DEGs) from the high- and low-risk groups. Using CIBERSORT, ESTIMATE, and single-sample GSEA (ssGSEA) algorithms, the quantities and types of tumor-infiltrating immune cells were assessed. The tumor mutational burden (TMB) and cytolytic (CYT) activity scores were calculated between the high- and low-risk groups. Potential small-molecule agents were identified using the Connectivity Map (cMap) database and validated by molecular docking. To verify key core gene expression levels, quantitative real-time polymerase chain reaction (qRT-PCR) assays were conducted. Results: We identified four distinct molecular subtypes of COAD. Cluster 2 had the best prognosis, and clusters 1 and 3 had poor prognoses. High-risk COAD patients exhibited considerably poorer overall survival (OS) than low-risk COAD patients. The nomogram precisely predicted patient OS, with acceptable discrimination and excellent calibration. GO and KEGG pathway enrichment analyses of DEGs revealed enrichment mainly in the "glycosaminoglycan binding," "extracellular matrix," "pancreatic secretion," and "focal adhesion" pathways. Patients in the low-risk group exhibited a larger infiltration of memory CD4+ T cells and dendritic cells and a better prognosis than those in the high-risk group. The chemotherapeutic agent sensitivity of patients categorized by risk score varied significantly. We predicted six potential small-molecule agents binding to the core target of the glycolysis- and lactate-related gene signature. ALDOB and APOBEC1 mRNA expression was increased in COAD tissues, whereas CLCA1 and OLFM4 mRNA expression was increased in normal tissues. Conclusion: In summary, we identified molecular subtypes of COAD and developed a glycolysis- and lactate-related gene signature with significant prognostic value, which benefits COAD patients by informing more precise and effective treatment decisions.

High-quality genome assembly and pan-genome studies facilitate genetic discovery in mung bean and its improvement.

Mung bean is an economically important legume crop species that is used as a food, consumed as a vegetable, and used as an ingredient and even as a medicine. To explore the genomic diversity of mung bean, we assembled a high-quality reference genome (Vrad_JL7) that was ∼479.35 Mb in size, with a contig N50 length of 10.34 Mb. A total of 40,125 protein-coding genes were annotated, representing ∼96.9% of the genetic region. We also sequenced 217 accessions, mainly landraces and cultivars from China, and identified 2,229,343 high-quality single-nucleotide polymorphisms (SNPs). Population structure revealed that the Chinese accessions diverged into two groups and were distinct from non-Chinese lines. Genetic diversity analysis based on genomic data from 750 accessions in 23 countries supported the hypothesis that mung bean was first domesticated in south Asia and introduced to east Asia probably through the Silk Road. We constructed the first pan-genome of mung bean germplasm and assembled 287.73 Mb of non-reference sequences. Among the genes, 83.1% were core genes and 16.9% were variable. Presence/absence variation (PAV) events of nine genes involved in the regulation of the photoperiodic flowering pathway were identified as being under selection during the adaptation process to promote early flowering in the spring. Genome-wide association studies (GWASs) revealed 2,912 SNPs and 259 gene PAV events associated with 33 agronomic traits, including a SNP in the coding region of the SWEET10 homolog (jg24043) involved in crude starch content and a PAV event in a large fragment containing 11 genes for color-related traits. This high-quality reference genome and pan-genome will provide insights into mung bean breeding.