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Abstract Background Myelodysplastic syndromes (MDS) are heterogeneous and clonal hematological disorders. The role and mechanism of necroptosis in MDS remain poorly understood. Methods mRNA expression profiles and single-cell RNA-sequencing (scRNA-seq) data were sourced from the GEO database. ScRNA-seq data were processed using the “Seurat” package. After cell annotation, necroptosis-related scores (NRscores) for each cell were calculated using the “UCell” package. Differentially expressed genes (DEGs) and their associated biological functions in NRscore-related cell populations were identified. Additionally, DEGs and necroptosis-related genes (DE-NRGs) between MDS patients and healthy controls were identified. Consensus clustering was employed to classify MDS patients into distinct subclusters based on DE-NRGs. The biological functions and immune characteristics of these classifications were analyzed. Prognostic gene signatures were determined using LASSO and SVM-RFE analyses, and a nomogram was constructed based on the prognostic gene signature. Results A total of 12 cell types were identified in MDS and healthy controls. NRscore was found to be elevated in monocytes and common lymphoid precursors (CLPs). Enrichment analysis revealed that monocytes and CLPs with high NRscore were associated with mitochondria-related and immune-related pathways. Eleven DEGs in monocytes and CLPs between MDS patients and healthy controls were identified. Additionally, 13 DE-NRGs were identified from 951 DEGs between MDS and healthy controls. MDS patients were classified into two distinct subclusters based on these 13 DE-NRGs, revealing several immune-related processes and signaling pathways. Differences in immune subpopulations between the two subclusters were observed. A necroptosis-related diagnostic gene signature (IRF9, PLA2G4A, MLKL, BAX, JAK2, and STAT3) was identified as predictive of MDS prevalence. Conclusion Necroptosis plays a role in MDS progression by inducing inflammation. A novel necroptotic gene signature has been developed to distinguish and diagnose MDS at early stages of the disease.

BackgroundThis randomized controlled trial aimed to compare the effects of butorphanol and sufentanil on early post-operative cognitive dysfunction (POCD) and systemic inflammation in older surgical patients.MethodsPatients (aged 65 years or above) undergoing surgeries with general anesthesia were randomized to either the butorphanol group (40 μg/kg during anesthesia induction) or the sufentanil group (0.4 μg/kg). Cognitive function changes during the perioperative period were assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) scale up to 3 days after surgery. POCD was defined as a Z-score or composite Z-score greater than 1.96 for both MMSE and MoCA scores. Circulating inflammatory factors, including tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 10 (IL-10), were measured using enzyme-linked immunosorbent assay.ResultsThe study included 114 patients (median age: 71 years, 57.7% male). Compared to sufentanil, butorphanol significantly reduced the incidence of POCD on the first (11.5% versus 32.7%, p = 0.017) and third day (3.8% versus 15.4%, p = 0.046) after surgery. Additionally, patients receiving butorphanol had significantly lower circulating levels of TNF-α and IL-1β at the time of discharge from the post-anesthesia care unit and on the first and third day after surgery (p

One of the hallmarks of cancer is metabolic reprogramming in tumor cells, and aerobic glycolysis is the primary mechanism by which glucose is quickly transformed into lactate. As one of the primary rate-limiting enzymes, pyruvate kinase (PK) M is engaged in the last phase of aerobic glycolysis. Alternative splicing is a crucial mechanism for protein diversity, and it promotes PKM precursor mRNA splicing to produce PKM2 dominance, resulting in low PKM1 expression. Specific splicing isoforms are produced in various tissues or illness situations, and the post-translational modifications are linked to numerous disorders, including cancers. hnRNPs are one of the main components of the splicing factor families. However, there have been no comprehensive studies on hnRNPs regulating PKM alternative splicing. Therefore, this review focuses on the regulatory network of hnRNPs on PKM pre-mRNA alternative splicing in tumors and clinical drug research. We elucidate the role of alternative splicing in tumor progression, prognosis, and the potential mechanism of abnormal RNA splicing. We also summarize the drug targets retarding tumorous splicing events, which may be critical to improving the specificity and effectiveness of current therapeutic interventions.

As a “medicine food homology” plant, the Piper betle L. has the characteristics of spicy, slightly sweet, and warm in nature, which can be used for treating cold, cough, stomachache, and eczema. The leaves have a strong and spicy aromatic smell and are widely used in chewables in Asia. Chemical analysis showed that the Piper betle L. contains nutrients and other chemical ingredients, including protein, starch, fat, essential oils, phenols, alcohols, ketones and alkaloids, etc. Modern pharmacological studies suggest that Piper betle L. is qualified with antimicrobial, antioxidant, anticancer, insect-resistant, anti-inflammatory, anti-malaria, and anti-glycosylation effect and so on. This article systematically reviews the material foundation and biological activity of Piper betle L., providing a reference for the further research and rational development.

Background: Pancreatic adenocarcinoma (PAAD) is one of the most common malignant tumors with high mortality rates and a poor prognosis. There is an urgent need to determine the molecular mechanism of PAAD tumorigenesis and identify promising biomarkers for the diagnosis and targeted therapy of the disease. Methods: Three GEO datasets (GSE62165, GSE15471 and GSE62452) were analyzed to obtain differentially expressed genes (DEGs). The PPI networks and hub genes were identified through the STRING database and MCODE plugin in Cytoscape software. GO and KEGG enrichment pathways were analyzed by the DAVID database. The GEPIA database was utilized to estimate the prognostic value of hub genes. Furthermore, the roles of MMP14 and COL12A1 in immune infiltration and tumor-immune interaction and their biological functions in PAAD were explored by TIMER, TISIDB, GeneMANIA, Metascape and GSEA. Results: A total of 209 common DEGs in the three datasets were obtained. GO function analysis showed that the 209 DEGs were significantly enriched in calcium ion binding, serine-type endopeptidase activity, integrin binding, extracellular matrix structural constituent and collagen binding. KEGG pathway analysis showed that DEGs were mainly enriched in focal adhesion, protein digestion and absorption and ECM-receptor interaction. The 14 genes with the highest degree of connectivity were defined as the hub genes of PAAD development. GEPIA revealed that PAAD patients with upregulated MMP14 and COL12A1 expression had poor prognoses. In addition, TIMER analysis revealed that MMP14 and COL12A1 were closely associated with the infiltration levels of macrophages, neutrophils and dendritic cells in PAAD. TISIDB revealed that MMP14 was strongly positively correlated with CD276, TNFSF4, CD70 and TNFSF9, while COL12A1 was strongly positively correlated with TNFSF4, CD276, ENTPD1 and CD70. GSEA revealed that MMP14 and COL12A1 were significantly enriched in epithelial mesenchymal transition, extracellular matrix receptor interaction, apical junction, and focal adhesion in PAAD development. Conclusions: Our study revealed that overexpression of MMP14 and COL12A1 is significantly correlated with PAAD patient poor prognosis. MMP14 and COL12A1 participate in regulating tumor immune interactions and might become promising biomarkers for PAAD.

Background Radioresistance is still the major cause of radiotherapy failure and poor prognosis in patients with non-small cell lung cancer (NSCLC). Apatinib (AP) is a highly selective inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2). Whether and how AP affects radiosensitivity in NSCLC remains unknown. The present study aimed to explore the radiosensitization effect of AP in NSCLC and its underlying mechanism as a radiosensitizer. Methods The NSCLC cell lines A549 and LK2 were treated with AP, ionizing radiation (IR), or both AP and IR. Expression of VEGFR2 was analyzed by western blot and RT-PCR. Cell proliferation was measured using CCK-8 and colony formation assays. Apoptosis and cell cycle distribution in NSCLC cells were analyzed by flow cytometry. Nuclear phosphorylated histone H2AX foci immunofluorescence staining was performed to evaluate the efficacy of the combination treatment. Western blot was used to explore the potential mechanisms of action. Results AP inhibited cell proliferation in a dose- and time-dependent manner. Flow cytometry analysis indicated that AP significantly increased radiation-induced apoptosis. Colony formation assays revealed that AP enhanced the radiosensitivity of NSCLC cells. AP strongly restored radiosensitivity by increasing IR-induced G2/M phase arrest. AP effectively inhibited repair of radiation-induced DNA double-strand breaks. Western blot analysis showed that AP enhanced radiosensitivity by downregulating AKT and extracellular signal-regulated kinase (ERK) signaling. Conclusion Our findings suggest that AP may enhance radiosensitivity in NSCLC cells by blocking AKT and ERK signaling. Therefore, AP may be a potential clinical radiotherapy synergist and a novel small-molecule radiosensitizer in NSCLC. Our study fills a gap in the field of anti-angiogenic drugs and radiosensitivity.

Background The nuclear factor I (NFI) is a family of transcription factors consisting of four distinct but closely related genes, NFIA, NFIB, NFIC and NFIX, which are important in the development of various tissues and organs in mammals. Recent study results have shown that NFI family may play a critical role in the progression of various human tumors and have been identified as key tumor suppressors and oncogenes for many cancers. However, the expression levels and distinctive prognostic values of the NFI family remain poorly explored in most cancers. Materials and Methods In the present study, the differences in mRNA expression of the NFI family in various cancers were investigated using the Oncomine and TCGA databases, and the mRNA expression, genetic alteration and DNA methylation of the NFI family members in various cancers were examined using cBioPortal for Cancer Genomics. In addition, the prognostic significance of the NFI family was assessed in multiple cancers using the Kaplan–Meier plotter (KM plotter) and SurvExpress databases. Results The mRNA expression levels in the NFI family were significantly downregulated in most cancers compared with normal tissues and DNA hypermethylation might downregulate the NFI family expression. Although NFIX expression was not downregulated in kidney, colorectal and prostate cancers. Furthermore, NFIB expression was upregulated in gastric cancer. Further survival analyses based on the KM plotter and SurvExpress databases showed dysregulations of the NFI genes were significantly correlated with survival outcomes in breast, lung, and head and neck cancers. Decreased expression levels of NFIA, NFIB and NFIC were associated with poor overall survival (OS) in head and neck cancer. Low mRNA expression of NFIA and NFIB was significantly associated with OS and first progression in lung adenocarcinoma, but not in lung squamous cell carcinoma. In addition, potential correlations between NFI family members and survival outcomes were also observed in liver, esophageal, kidney and cervical cancer. Conclusion The results from the present study indicated certain members of the NFI family could be promising therapeutic targets and novel prognostic biomarkers for human cancers.

Abstract Intensified industrial activities significantly threaten farmland soil integrity, particularly in salinized regions. However, comprehensive evaluations of soil fertility and contamination by polycyclic aromatic hydrocarbons (PAHs) remain limited. In this study, we assessed soil quality in China’s Yellow River Delta (YRD) by quantifying 13 indicators of soil physicochemical and biological properties, along with 11 PAHs. Our findings reveal that the minimum data set approach provides a robust and comprehensive representation of overall soil fertility. Salinity emerged as the primary limiting factor, with strong correlations between salinity and key ions, highlighting its adverse effects on soil structure and function. Additionally, significant PAH contamination was detected, particularly from benzo[a]anthracene (BaA), fluoranthene (Flu), and chrysene (Chr), as indicated by the Nemerov pollution index. A pronounced negative correlation between the soil quality index (SQI) and the soil environmental index (SEI) underscores the substantial role of PAH pollution in soil degradation. Notably, the SQI integrates both SEI and soil fertility, providing a holistic assessment of soil health. These findings highlight the utility of SQI as a diagnostic tool for evaluating soil degradation and emphasize the need for targeted remediation strategies to address salinity and PAH contamination, thereby promoting soil restoration and agricultural sustainability.

The accurate identification and assessment of comprehensive risks associated with compound pollution in agricultural ecosystems remain significant challenges due to the complexity of pollution sources, soil heterogeneity, and spatial variability. In this study, bivariate local indicators of spatial association (LISA) were applied to analyze the spatial interaction between heavy metals (HMs) and polycyclic aromatic hydrocarbons (PAHs) in farmland soils in Hezhang County. The results revealed distinct clusters with elevated concentrations of both HMs and PAHs, predominantly in areas affected by long-standing lead-zinc mining and smelting activities. Positive matrix factorization (PMF) was utilized to identify mining and smelting activities, and associated coal consumption as common sources of both pollutants, contributing 53 % and 28 %, respectively. Ecological health risk assessment results indicated that the combined pollution in this area has led to particularly severe ecological and cancer risks, with the pollution coefficient (Pc) exceeding 3.0, and risk values for both adults and children surpassing the threshold of 10−4. Through the integration of advanced bivariate LISA mapping and thorough risk assessment, this study precisely delineated ecological risk zones (33.1 %) and more refined health risk zones (40.1 %) associated with combined pollution. The southwest of Hezhang was identified as a critical hotspot for combined pollution risks, primarily due to intensive mining and smelting activities in the region. Overall, this study underscores the utility of bivariate LISA as a robust approach for delineating spatial clustering patterns caused by combined pollutants. It provides crucial insights for identifying regions with heightened human health and ecological risks in rural settings.

Abstract Objective To explore the relative sensitivity of different methods for detecting cervical glandular lesions. Methods A total of 225 patients with cervical glandular lesions diagnosed from January 2018 to February 2023 were retrieved from the pathology database of Guangdong Maternal and Child Health Hospital, and their clinicopathological features were reviewed. Results Four human papillomavirus (HPV) genotypes: HPV18, 16, 45, and 52, dominated all glandular lesions, and accounting for 74.10% of HPV-positive tumors. Furthermore, 36.89% of abnormal squamous cells were diagnosed as abnormal based on cytological examinations leading to the detection of cervical glandular lesions; only 16.89% were diagnosed based on the initial detection of abnormal glandular cytology. The most common abnormal cervical screening result was ASC-US on cytology (14.22%), followed by HSIL (11.56%). Only few number of patients were diagnosed with or suspected of having cervical adenopathy via a Pap test (18.22%). Nearly one-third of cervical glandular lesions cases were not detected on the Pap test; but were diagnosed upon cervical biopsy or based on the histological examination of ECC, LEEP, or CKC specimens. The LEEP or CKC biopsy specimens had negative margins in 49 cases (40.83%), while the margins were positive in the other 71 cases (59.17%). Five cases (10.20%) with negative margins still had residual lesions following total hysterectomy, and 19 (26.76%) with positive margins had no residual lesions after total hysterectomy. Conclusion The ability to detect cervical glandular lesions varies for routine HPV genotyping, Pap test, or biopsy/ECC, with different sensitivities and advantages and disadvantages for each method.

The presence of polycyclic aromatic hydrocarbons (PAHs) in soil negatively affects the environment and the degradation of these contaminants is influenced by nitrogen metabolism. However, the mechanisms underlying the interrelationships between the functional genes involved in nitrogen metabolism and phenanthrene (PHE) biodegradation, as well as the effects of biochar on these mechanisms, require further study. Therefore, this study utilised metabolomic and metagenomic analysis to investigate primary nitrogen processes, associated functional soil enzymes and functional genes, and differential soil metabolites in PHE-contaminated soil with and without biochar amendment over a 45-day incubation period. Results showed that dissimilatory nitrate reduction to ammonium (DNRA) and denitrification were the dominant nitrogen metabolism processes in PHE-contaminated soil. The addition of biochar enhanced nitrogen modules, exhibiting discernible temporal fluctuations in denitrification and DNRA proportions. Co-occurrence networks and correlation heatmap analysis revealed potential interactions among functional genes and enzymes responsible for PHE biodegradation and nitrogen metabolism. Notably, enzymes associated with denitrification and DNRA displayed significant positive correlation with enzymes involved in downstream phenanthrene degradation. Of particular interest was stronger correlation observed with the addition of biochar. However, biochar amendment inhibited the 9-phenanthrol degradation pathway, resulting in elevated levels of glutathione (GSH) in response to environmental stress. These findings provide new insights into the interactions between nitrogen metabolism and PHE biodegradation in soil and highlight the dual effects of biochar on these processes.

BackgroundDeath education has been confirmed to be an effective method to enhance nursing students’ attitudes and coping abilities toward death. However, integrated Narrative Pedagogy into the death education to explore educational effectiveness is still limited. The study aimed to evaluate the effects of a death education based on Narrative Pedagogy in a palliative care course on the attitude toward death, coping with death, and attitude toward caring for the dying among undergraduate nursing students in China.MethodsThe study was designed as a pre-post intervention study with a quasi-experimental design. All the participants received 6 class hours of death education which was designed in a palliative care course. The death education includes preparation, presentation, discussion, reflection, and practice of the narrative materials. Death Attitude Profile-Revised (DAP-R), Coping with Death Scale (CDS), and Frommelt Attitude Toward Care of the Dying-Form B (FATCOD-Form B) were used to measure outcomes.ResultsSixty undergraduate nursing students who consented. There were statistically significant increases in the mean score of neutral acceptance and approach acceptance in the DAP-R, CDS, and FATCOD-Form B before and after the intervention.ConclusionThis death education integrated Narrative Pedagogy which indicated to improve attitude toward death, competence to cope with death, and attitude toward the care of dying patients. The findings assist teachers in understanding the importance and urgency of death education, as well as providing a favorable approach to death education. However, the long-term effectiveness still needs to study in further.

Abstract Background Polycyclic aromatic hydrocarbons (PAHs) pose a potential risk to ecological safety and human health. They have a range of effects on plant growth and there have been few reports on the health risks associated with ingestion of vegetable crops at different growth stages. Methodology In this study, a pot experiment in which Chinese cabbage (Brassica campestris L.) were grown in a greenhouse for 75 days was used to investigate the dose–effect relationship of pyrene with plant growth and also the exposure risk for adults of ingestion of Chinese cabbage at different growth stages. Results The results showed that low doses of pyrene (5–45 mg kg−1) promoted plant growth (20–220% and 55–97% higher than control treatment for the root biomass and shoot biomass, respectively), but significant inhibition was observed at a high dose (405 mg kg−1) (41–66% and 43–91% lower than control treatment for the root biomass and shoot biomass, respectively). High doses of pyrene reduced soil bacterial abundance and diversity during the growth of Chinese cabbage, and increased malondialdehyde (MDA) levels in the plant. The effects of pyrene on plant biomass were mainly attributed to changes in root activity induced by pyrene, as the relationship between soil pyrene concentration and biomass was similar to that between soil pyrene concentration and root activity. Furthermore, structural equation modeling analysis showed that pyrene altered growth of the vegetable by directly affecting root activity. The incremental lifetime cancer risk for adults is highest for ingestion of Chinese cabbage at the seedling stage, followed in decreasing order by the rosette stages and heading stages. Conclusions The health risk of consumers who have the possibility to ingest the Chinese cabbage planted in pyrene-contaminated soil would be decreased with the increasing growth periods. However, further studies are required to confirm the dose–effect relationship between pyrene concentration and Chinese cabbage growth on a field scale. Graphical Abstract

Most of the previous works on relation extraction between named entities are often limited to extracting the pre-defined types; which are inefficient for massive unlabeled text data. Recently; with the appearance of various distributional word representations; unsupervised methods for many natural language processing (NLP) tasks have been widely researched. In this paper; we focus on a new finding of unsupervised relation extraction; which is called distributional relation representation. Without requiring the pre-defined types; distributional relation representation aims to automatically learn entity vectors and further estimate semantic similarity between these entities. We choose global vectors (GloVe) as our original model to train entity vectors because of its excellent balance between local context and global statistics in the whole corpus. In order to train model more efficiently; we improve the traditional GloVe model by using cosine similarity between entity vectors to approximate the entity occurrences instead of dot product. Because cosine similarity can convert vector to unit vector; it is intuitively more reasonable and more easily converge to a local optimum. We call the improved model RGloVe. Experimental results on a massive corpus of Sina News show that our proposed model outperforms the traditional global vectors. Finally; a graph database of Neo4j is introduced to store these relationships between named entities. The most competitive advantage of Neo4j is that it provides a highly accessible way to query the direct and indirect relationships between entities.