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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. 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. 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. 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.

An attractive approach for the preparation of spirocyclic benzofuran–furocoumarins has been developed through iodine-catalyzed cascade annulation of 4-hydroxycoumarins with aurones. The reaction involves Michael addition, iodination, and intramolecular nucleophilic substitution in a one-step process, and offers an efficient method for easy access to a series of valuable spirocyclic benzofuran–furocoumarins in good yields (up to 99%) with excellent stereoselectivity. Moreover, this unprecedented protocol provides several advantages, including readily available materials, an environmentally benign catalyst, a broad substrate scope, and a simple procedure.

Background Helicobacter pylori ( H. pylori ) causes chronic gastric disease. An efficient oral vaccine would be mucosa-targeted and offer defense against colonization of invasive infection in the digestive system. Proteolytic enzymes and acidic environment in the gastrointestinal tract (GT) can, however, reduce the effectiveness of oral vaccinations. For the creation of an edible vaccine, L. lactis has been proposed as a means of delivering vaccine antigens. Results We developed a plSAM (pNZ8148-SAM) that expresses a multiepitope vaccine antigen SAM-WAE containing Urease, HpaA, HSP60, and NAP extracellularly (named LL-plSAM-WAE) to increase the efficacy of oral vaccinations. We then investigated the immunogenicity of LL-plSAM-WAE in Balb/c mice. Mice that received LL-plSAM-WAE or SAM-WAE with adjuvant showed increased levels of antibodies against H. pylori , including IgG and sIgA, and resulted in significant reductions in H. pylori colonization. Furthermore, we show that SAM-WAE and LL-plSAM-WAE improved the capacity to target the vaccine to M cells. Conclusions These findings suggest that recombinant L. lactis could be a promising oral mucosa vaccination for preventing H. pylori infection.

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.

Purpose. To elucidate the clinical and prognostic role of PDZ and LIM domain protein (PDLIM) genes and the association to epithelial-mesenchymal transition (EMT) and immune cell infiltration in patients with prostate cancer (PRAD). Methods. The data of RNA-seq, DNA methylation, and clinical features of PRAD patients were collected from The Cancer Genome Atlas (TCGA) database to define the prognostic value of PDLIM gene expression and the association with EMT and immune cell infiltration. A tissue microarray including 134 radical prostatectomy specimens was served as validation by immunohistochemistry (IHC) staining analysis. Results. The mRNA levels of PDLIM1/2/3/4/6/7 were significantly downregulated, while PDLIM5 was upregulated in PRAD (P<0.05). High expression of PDLIM2 mRNA suggests poor progression free interval in PRAD patients. DNA methylation of PDLIM2 was correlated with its mRNA expression level, and that the cg22973076 methylation site in PDLIM2 was associated with shorter PFI (P<0.05) in PRAD. Single-sample gene-set enrichment and gene functional enrichment results showed that PDLIM2 was correlated with EMT and immune processes. Spearman’s test showed a significant correlation with six reported EMT signatures and several EMT signature-related genes. Tumor microenvironment analysis revealed that the PDLIM2 mRNA expression was positively correlated with the immune score, stromal score, and various tumor infiltrating immune cells. Additionally, the results showed that patients in the high-PDLIM2 mRNA expression group may be more sensitive to immune checkpoint blockade therapy. Finally, IHC analysis further implicated the protein level of PDLIM2 was upregulated in PRAD and acts as a novel potential biomarker in predicting tumor progression. Conclusion. Our study suggests that PDLIM family genes might be significantly correlated with oncogenesis and the progression of PRAD. PDLIM2 correlated with EMT and immune cell infiltration by acting as an oncogene in PRAD, which may serve as a potential prognostic biomarker for PRAD patients.

The emergence of NDM-1 containing multi-antibiotic resistant \"Superbugs\" necessitates the needs of developing of novel NDM-1inhibitors. In this study, we report the discovery of novel NDM-1 inhibitors by multi-step virtual screening. From a 2,800,000 virtual drug-like compound library selected from the ZINC database, we generated a focused NDM-1 inhibitor library containing 298 compounds of which 44 chemical compounds were purchased and evaluated experimentally for their ability to inhibit NDM-1 in vitro. Three novel NDM-1 inhibitors with micromolar IC50 values were validated. The most potent inhibitor, VNI-41, inhibited NDM-1 with an IC50 of 29.6 ± 1.3 μM. Molecular dynamic simulation revealed that VNI-41 interacted extensively with the active site. In particular, the sulfonamide group of VNI-41 interacts directly with the metal ion Zn1 that is critical for the catalysis. These results demonstrate the feasibility of applying virtual screening methodologies in identifying novel inhibitors for NDM-1, a metallo-β-lactamase with a malleable active site and provide a mechanism base for rational design of NDM-1 inhibitors using sulfonamide as a functional scaffold.

Cervical cancer has the second-highest incidence and mortality of female malignancy. The major causes of mortality in patients with cervical cancer are invasion and metastasis. The epithelial–mesenchymal transition (EMT) process plays a major role in the acquisition of metastatic potential and motility. Autophagy-related genes (ARGs) are implicated in the EMT process, and autophagy exerts a dual function in EMT management at different phases of tumor progression. However, the role of specific ARGs during the EMT process has not yet been reported in cervical cancer. Based on the data from the Cancer Genome Atlas (TCGA) cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) sequencing database, we performed the prognosis analysis for those ARGs obtained from the Human Autophagy database. ATG5 was identified as the only important harmful marker influencing survival of cervical cancer patients by univariate Cox regression (HR 1.7; 95% CI: 1.0–2.8, p = 0.047), and the 5-years survival rate for the high- and low-ATG5 expression groups was 0.486 (0.375–0.631) and 0.782 (0.708–0.863), respectively. TCGA CESC methylation data showed that eight methylation sites of ATG5 could also be significantly associated with the overall survival (OS) of cervical cancer patients. Single-sample gene-set enrichment and gene functional enrichment results showed that ATG5 was correlated with some cancer-related pathways, such as phagocytosis-related genes, endocytosis-related genes, immune-related genes, EMT score, and some EMT signature-related genes. Next, cell migration and invasion assay and Western blot were applied to detect the function of ATG5 in EMT of cervical cancer. In cervical cancer cells, ATG5 knockdown resulted in attenuation of migration and invasion. The functional study showed that knockdown of ATG5 could reverse EMT process by P-ERK, P-NFκBp65, P-mTOR pathways, and so on. In conclusion, the present study implies that ATG5 was a major contributor to EMT regulation and poor prognosis in cervical cancer.

An attractive approach for the preparation of pyrrolo[2,3- d ]pyrimidines has been developed via I 2 /DMSO promoted cascade annulation of 6-amino-1,3-dimethyluracil with aurones. The reaction involves Michael addition, iodination, intramolecular nucleophilic substitution, and spiro ring opening in one-step process, and affords a series of natural product analogues containing pyrrolo[2,3- d ]pyrimidine in good yields (up to 99%). Additionally, this protocol exhibits the advantages of high atom economy, inexpensive catalyst, readily available materials, convenient operation and applicability for large-scale synthesis.

The morphology and stability of concave surface of the straw checkerboard barriers are the fundamental guiding principles of exploring the mechanism of erosion and deposition, evaluating effectiveness and life period, and optimizing the physical structures of the sand barriers. Especially, in alpine sandy land, characteristics of erosion (deposition) and capacity for anti-erosion and sand burial of straw checkerboard barriers are significantly different from the arid and semi-arid desert regions. Erosion (deposition) measurements and wind–sand observations for different specifications (1 m × 1 m, 1.5 m × 1.5 m and 2 m × 2 m) and slope positions (toe, middle and top of the windward areas) of wheat straw checkerboard barriers were adopted in the eastern shore of the Qinghai Lake study area. The different sizes of straw checkerboards at different windward areas have distinctly erosive and depositional stability and intensity. Including the checkerboards with 1.5 m × 1.5 m (medium) size at the middle and top, 1 m × 1 m (small) size at the top and 2 m × 2 m (large) size at the toe, all the erosion (deposition) coefficients are between 0.09 and 0.11, while their intensities of accumulation are relatively steady (70–90 kg m⁻²), which are the easiest to form stable concaves, and the heights of the barriers change least. Nevertheless, the concaves with small size at the toe are seriously buried, but eroded in the center of some checkerboards with large size at the top, which lead to a short protective period within 3 years and an unbalance between erosion and deposition. Moreover, the transects of erosion (deposition) dominated by southwesterly and northwesterly winds reflect the different intensities of erosion (deposition) at various orientations. On the transect of the NW–SE orientation, at the dune section, each square in the NW direction is strongly accumulated, and the center–SE azimuth is weakly eroded. Usually, deeper accumulation in the center of transects happen in those checkerboards with smaller size and lower terrain slope, which is mainly caused by an obviously positive correlation between the northwest and southwest wind velocity and the erosive depth, and the same is true with the wind frequency (all correlation coefficients are between 0.85 and 0.95). Taking the characteristics of erosion (deposition), sand protection benefits and costs of all types into account, large size at the toe and medium size at the middle of windward slope are the most practical combinations, while small size is suitable to play an emergency treatment role in some extremely serious hazard areas in alpine sandy land.

[This corrects the article DOI: 10.3389/fcell.2021.757184.].