Xuequan Wang

Background: Cystic echinococcosis (CE), caused by Echinococcus granulosus , is a zoonotic disease with major global social and economic impacts. Research on its burden in children and adolescents remains limited. This study evaluates the global CE burden from 1990 to 2021 and projects future trends, supporting WHO NTD Roadmap goals aimed at enhancing control in 17 high-endemic countries by 2030. Methods: Using the Global Burden of Disease (GBD) database, we assessed prevalence, incidence, deaths, DALYs, YLDs, and YLLs due to CE in individuals aged 0–19 at global, regional, and national levels. We computed age-standardized rates (ASRs) and estimated annual percentage changes (EAPCs). Additional analyses included joinpoint regression, inequality measures, frontier and decomposition analysis, age-period-cohort (APC) modeling, Socio-demographic Index (SDI) correlations, and future trend prediction. Results: Over 32 years, the global CE burden declined overall, though disparities persisted. Low SDI regions had high ASPR, ASIR, and ASMR. In 2021, global ASIR was 1.12 per 100,000, ASPR was 3.71, and ASMR was 0.01. Moldova had the highest ASPR; Iceland the lowest. East Asia saw growth in ASPR and ASIR. South Sudan had the highest ASMR; Ethiopia had the highest ASDR. Females showed higher ASPR and ASIR; males had higher ASMR. A strong negative correlation was observed between SDI and health indicators. Population changes primarily influenced ASPR. Frontier analysis indicated elevated ASMR/ASDR in some low-SDI nations and rising trends in certain high SDI countries. Age-specific prevalence increased with age. Projections suggest a slow decline in CE burden over the next 25 years, though some countries will remain severely affected. Conclusions: The global CE burden in children and adolescents decreased from 1990 to 2021, yet challenges remain, especially in low-SDI regions such as Sub-Saharan Africa and Central Asia. The Slope Index of Inequality (SII) for ASPR narrowed from -2.597 to -1.087, reflecting reduced but persistent disparity. Rising ASMR and ASDR in high SDI countries like Germany and Norway underscore the need for targeted interventions. The negative SDI health correlation highlights socioeconomic influences. Prevention should focus on females in low-SDI areas, while improved medical care is needed for males facing higher mortality. Although a continued decline is projected, sustained efforts are essential in high burden countries. These findings, supported by a improving concentration index (CI) for ASPR (-0.358 to -0.218), reveal critical health inequalities and inform public health strategies.

Dietary microRNAs have attracted increasing attention in the field of aging research due to their potential regulatory roles, highlighting a novel direction for nutritional strategies in anti-aging interventions.

Lymph node metastasis significantly affects the NSCLC patients' staging, treatment strategy, and prognosis. Studies have shown that IGF2BP3, an oncofetal protein and an m6A reader, overexpresses and correlates to lymph node metastasis and worse overall survival in histopathological studies including NSCLC, but its mechanism needs further study. This study explored IGF2BP3's function and mechanism in LUAD lymphatic metastasis using public databases, a human LUAD tissue microarray, human LUAD cells, and a lymphatic metastasis model in male BALB/c nude mice. Firstly, we proved that IGF2BP3 overexpression was positively correlated to patients' lymph node metastasis and worse overall survival in bioinformatics and a human LUAD tissue microarray analysis. IGF2BP3 was knocked out or overexpressed in human LUAD cell lines. Functionally, IGF2BP3 facilitated NCI‐H1299, NCI‐H358, and A549 cell growth, migration, invasion, and EMT in vitro, and promoted tumorigenesis, lymphangiogenesis, and lymphatic metastasis of NCI‐H1299 cells in BALB/c nude mice. Mechanically, RIP, RNA pull‐down assay, MeRIP, mRNA stability assays, rescue experiments, and immunohistochemical assays were conducted. IGF2BP3 was demonstrated to bind to the m6A site of the 3′UTR region of SRC, stabilizing its mRNA and activating the downstream STAT3 signaling pathway and lymphatic growth factors such as VEGF‐C, therefore affecting lymphatic metastasis. The cell migration and EMT function of IGF2BP3 were partially rescued by utilizing SRC siRNA or AZD0530, an SRC inhibitor. This study demonstrated that IGF2BP3 promotes lymphatic metastasis in LUAD via activating the m6A‐SRC‐STAT3‐VEGFC signaling axis, indicating that IGF2BP3 is a potential therapeutic target to overcome metastasis in LUAD patients.

Background: Tumor initiation and metastasis influence tumor immune exclusion and immunosuppression. Long non-coding RNA (lncRNA) LINC01614 is associated with the prognosis and metastasis of several cancers. However, the relationship between LINC01614 and cancer immune infiltration and the biofunction of LINC01614 in head and neck squamous cell carcinoma (HNSC) remain unclear.Methods: The Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets were used to analyze the expression difference and diagnostic value of LINC01614 in normal and tumor tissues. The correlation of pan-cancer prognosis and tumor stage of LINC01614 was analyzed based on the TCGA database. The pan-cancer association of LINC01614 expression with the tumor microenvironment (TME) including immune infiltration, expression of immune-related genes, and genomic instability parameters, was analyzed using the Spearman correlation method. The correlation between LINC01614 and tumor stemness evaluation indicators, RNA methylation-related genes, and drug resistance was also analyzed. The functional analysis of LINC01614 was performed using the clusterProfiler R package. The protein–protein interaction (PPI) network and ceRNA network of LINC01614 co-expressed genes and miRNA were constructed and visualized by STRING and Cytoscape, respectively. Finally, the cell location and influence of LINC01614 on cell proliferation and metastasis of HNSC cell lines were evaluated using FISH, CCK-8, wound-healing assay, and transwell assay.Results: LINC01614 was found to be overexpressed in 23 cancers and showed a highly sensitive prediction value in nine cancers (AUC >0.85). LINC01614 dysregulation was associated with tumor stage in 12 cancers and significantly influenced the survival outcomes of 26 cancer types, with only Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC), uterine corpus endometrial carcinoma (UCEC), and bladder urothelial carcinoma (BLCA) showing a benign influence. LINC01614 was also associated with immune cell infiltration, tumor heterogeneity, cancer stemness, RNA methylation modification, and drug resistance. The potential biological function of LINC01614 was verified in HNSC, and it was found to play important roles in proliferation, immune infiltration, immunotherapy response, and metastasis of HNSC.Conclusion: LINC01614 may serve as a cancer diagnosis and prognosis biomarker and an immunotherapy target for specific cancers.

The acidic environment and enzyme degradation lead to oral vaccines often having little immune effect. Therefore, it is an attractive strategy to study an effective and safe oral vaccine delivery system that can promote gastrointestinal mucosal immune responses and inhibit antigen degradation. Moreover, the antigens uptake by microfold cells (M cells) is the determining step in initiating efficient immune responses. Therefore, M cell-targeting is one promising approach for enhancing oral vaccine potency. In the present study, an M cell-targeting L. lactis surface display system (plSAM) was built to favor the multivalent epitope vaccine antigen (FAdE) to achieve effective gastrointestinal mucosal immunity against Helicobacter pylori. Therefore, a recombinant Lactococcus lactic acid vaccine (LL-plSAM-FAdE) was successfully prepared, and its immunological properties and protective efficacy were analyzed. The results showed that LL-plSAM-FAdE can secretively express the recombinant proteins SAM-FAdE and display the SAM-FAdE on the bacterial cell surface. More importantly, LL-plSAM-FAdE effectively promoted the phagocytosis and transport of vaccine antigen by M cells in the gastrointestinal tract of mice, and simulated high levels of cellular and humoral immune responses against four key H. pylori adhesins (Urease, CagL, HpaA, and Lpp20) in the gastrointestinal tract, thus enabling effective prevention of H. pylori infection and to some extent eliminating H. pylori already present in the gastrointestinal tract. Key points: • M-cell-targeting L. lactis surface display system LL- plSAM was designed • This system displays H. pylori vaccine-promoted phagocytosis and transport of M cell • A promising vaccine candidate for controlling H. pylori infection was verified

The author made a relatively detailed analysis of the impact of LSD1 on triple negative breast cancer, but I think this article needs a lot of adjustment before it is published. 1.The author emphasized many aspects of epigenetics, but the article did...

Background: Hepatocellular carcinoma (HCC) is the second malignancy worldwide. POLA2 initiates DNA replication, regulates cell cycle and gene repair that promote tumorigenesis and disease progression. However, the prognostic and biological function roles of POLA2 in HCC had not been conclusively determined. Methods: The expression levels and prognosis role of POLA1 and POLA2 in HCC were analyzed based on TCGA-LIHC database and recruited 24 HCC patients. Gene mutations were analyzed using “maftools” package. POLA2 and immune cells correlations were analyzed by TIMER. POLA2 co-expressed genes functional enrichment were evaluated using Metascape. The mRNA and protein level of POLA2 was detected in HCC cells and tissues. Cell migration, invasion, proliferation, cell cycle and HCC cell lines derived xenograft model were performed to investigate POLA2 biological function. Results: POLA2 was significantly high expressed in HCC than in normal liver tissue in both TCGA-LIHC and our collected HCC samples. In validation cohort, POLA2 significantly related to tumor differentiation, tumor size and Ki-67 (p < 0.05). In TCGA-LIHC cohort, overexpression of POLA2 predicted a low OS and associated with different clinical stages. Multivariate Cox regression showed overexpression of POLA2 effectively distinguished the prognosis at different T, N, M, stages and grades of HCC. POLA2 expression correlated with mutation burden, immune cells infiltration and immune-associated genes expression of HCC. Functional enrichment revealed that POLA2 co-expressed genes were linked to cellular activity, plasma membrane protein complex and leukocyte activity, immune response-regulated cell surface receptor signaling pathway, and immune response-regulated signaling pathway. Moreover, POLA2 was also positively co-expressed with some immune checkpoints (CD274, CTL-4, HAVCR2, PDCD1, PDCD1LG2, TIGIT, and LAG3) (p < 0.001). Gene knockdown revealed that POLA2 promoted proliferation, migration, invasion, and cell cycle of SMMC-7721 and HepG2. The HCC xenograft tumor model also demonstrated remarkably tumor size inhibition, tumor proliferation inhibtion and tumor necrosis promotion when POLA2 knockdown. Conclusions: POLA2 influenced immune microenvironment and tumor progression of HCC indicated that it might be a potential molecular marker for prognostic evaluation or a therapeutic target for HCC.

Corrigendum: High expression of nectin-1 indicates a poor prognosis and promotes metastasis in hepatocellular carcinoma

A Novel Prognosis Signature Based on Ferroptosis-Related Gene DNA Methylation Data for Lung Squamous Cell Carcinoma: Ferroptosis-related genes regulating an iron- and lipid reactive oxygen species (ROS)-dependent form of programmed cell death suggest critical roles for ferroptosis in cancers. However, the prognostic value of ferroptosis-related epigenetic features such as DNA methylation in lung squamous cell carcinoma (LUSC) needs to be studied. Ferroptosis-related genes are collected from the FerrDb database, and the methylation data of these related genes in LUSC methylation data downloaded from the TCGA are retrieved. The DNA methylation data (362 LUSC samples) were analyzed to screen prognostic ferroptosis-related methylation sites. After patients with complete overall survival (OS) information were randomly separated into training cohort (n = 200) and validation cohort (n = 162), the least absolute shrinkage and selection operator (LASSO) and the Cox regression were used to establish and validate the prognostic signature. The time-dependent receiver operating characteristic (ROC) and KaplanMeier survival curve analyses, Harrells concordance index (C-index), calibration analysis, and decision curve analysis (DCA) were performed to evaluate the risk signature and related nomogram. A series of other bioinformatics approaches such as mexpress, cbioportal, maftools, string, metascape, TIMER, and KaplanMeier survival curve analysis were also used to determine the methylation, mutation status, protein interaction network or functional enrichment, effects on immune cell infiltration, or expression level prognosis of those signature-related genes. A total of 137 DNA methylation sites were identified as prognostic predictors corresponding to 109 ferroptosis-related genes (FRGs). The methylation signature containing 31 methylation sites proved to be superior predictive efficiency in predicting the 1-, 3-, 5-, and 10-year OS. 8 out of 28 signature-related genes were significantly related to OS time or OS state in patients with LUSC. In addition, DUSP1, ZFN36, and ALOX5 methylation status also correlated with pathological M and ALOX5 methylation correlated with pathological N. The prognostic prediction efficiency of T, N, M, and the stage was inferior to that of the DNA methylation signature. LUSC patients in the high-risk group own a significantly larger number of variants of FRGs than those in the low-risk group. In addition, negative or positive correlation patterns were presented among the different infiltrating immune cells with risk scores or signature-related genes in patients with LUSC. The expression level of 15 signature-related genes showed a significant relationship with OS of LUSC patients. A novel prognostic nomogram survival model containing 4 factors including age, pathologic T, stage, and risk group was constructed and validated, AndC-index, decision curve analysis (DCA), and calibration analysis demonstrated its excellent predictive performance. The FRG DNA methylation data-based prognostic model acts as a powerful prognostic prediction indicator in LUSC patients and is advantageous over the traditional model based on T, N, M, and stage.

Objectives: Nectins are a new class of cell-adhesion molecules that play an important role in tumorigenesis and disease progression. The aim of this study was to investigate the prognostic and pathogenetic roles of nectins in hepatocellular carcinoma (HCC).Methods: The expression levels of the nectin family in HCC and their role in prognosis were analyzed by bioinformatics analysis based on The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma database. The correlations between nectins and immune cells were analyzed using TIMER. The functional enrichment of the nectin-1 coexpression network was evaluated in TCGA cohort, and the expression levels of nectin-1 were detected by immunohistochemistry and Western blot analysis. A Transwell kit was used for cell migration experiments. Cell proliferation was analyzed using Cell Counting Kit-8.Results: The expression levels of nectin-1 protein in the cancer tissues of 28 patients with HCC were higher than those in paracancerous tissues. The Kaplan–Meier plotter analysis showed that the high expression of all nectin family numbers was related to the poor prognosis of HCC patients. The abnormal expression of nectin-1 effectively distinguished the prognosis at different stages and grades of HCC. The high expression of 17 methylation sites of the nectin-1 gene was related to the high overall survival of HCC patients. Kyoto Encyclopedia of Genes and Genomes analysis of genes negatively correlated with nectin-1, revealing their close relation to the regulation of the immune-effector process. Pearson’s correlation analysis showed that nectin-1 was significantly positively correlated with multiple immune genes and B cells, CD4⁺ T cells, macrophages, neutrophils, and dendritic cell infiltration. Cell proliferation of the knockdown (KD) group decreased significantly compared to the NC-KD group. The number of metastatic cells in the KD group decreased significantly compared to that in the NC-KD group.Conclusions: Abnormal expression of nectins and multiple methylation sites closely correlates with poor prognosis in HCC patients. Nectins are related to immune cell infiltration and immune-related genes. In particular, nectin-1 can promote the proliferation and migration of liver cancer cells and distinguish the prognosis at different stages and grades of HCC. Nectin-1 might be a new potential molecular marker for prognostic evaluation and also a therapeutic target for HCC.