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Background and objective In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. Methods A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. Results MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P more...

Background and objective The morbidity and mortality rates of lung cancer remain high worldwide, and lung adenocarcinoma is one of the most important tissue subtypes of lung cancer. Epidermal growth factor receptor (EGFR) mutation is an important driver gene mutation for lung adenocarcinoma. In recent years, immune checkpoint inhibitors (ICIs), such as programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, have achieved remarkable efficacy in some lung cancer patients. Patients with EGFR mutations enjoyed limited benefits from immunotherapy according to recent studies. This study aimed to explore the relationship between EGFR mutation status and the spatial distribution as well as infiltration number of various immune cells in patients with EGFR mutant lung adenocarcinoma. Methods This study included 62 lung adenocarcinoma patients who underwent surgery. Through multi-point sampling of surgically removed tumor tissues in different areas, 223 tumor tissue samples were finally obtained. We aquired EGFR mutations status including variant allele frequency (VAF) and mutation subtype in each tumor tissue by genetic test. Afterwards, hematoxylin-eosin (HE) staining, immunohistochemical staining and multiplex fluorescence immunohistochemistry staining have been performed, therefore the infiltration of various immune cells and the distribution of tertiary lymphoid structure (TLS) in tumor tissues were obtained by calculating the immunohistochemical score. Results Compared with EGFR wild-type patients, patients with EGFR-mutant lung adenocarcinoma had more infiltration of CD68+ macrophages and major histocompatibility complex (MHC) class II antigen-presenting cells and higher spatial distribution heterogeneity of MHC class II antigen presenting cells in tumor tissues, while CD56+ natural killer cells and CD8+ T cells had lower infiltration. Tumor tissues with higher EGFR VAF were associated with lower cell infiltration such as CD3+ T cells, CD20+ B cells, CD56+ natural killer cells, CD68+ macrophages, CD8+ T cells, and only CD3+ T cells showed a lower spatial distribution heterogeneity. For the two common subtypes of EGFR mutations in Chinese population, tumor tissues with EGFR exon 19 deletion mutations have lower immune cell infiltration but higher spatial distribution heterogeneity of CD3+ T cells, CD56+ natural killer cells, CD68+ macrophages, and CD8+ T cells than that in EGFR exon 21 L858R mutant tumor tissues. Prognostic analysis found that patients with EGFR mutations with high degree of CD3+ T cells, CD20+ B cell infiltration and larger numbers of TLS formation and high spatial distribution heterogeneity of CD8+ T cell had longer disease-free survival. Conclusion EGFR-mutated lung adenocarcinoma had a unique "non-inflammatory" tumor microenvironment with low infiltration of immune cells, and there was also heterogeneity in the tumor microenvironment among the tumors with different mutation subtypes and mutation abundance. These differences were not only reflected in the number but also the spatial distribution of immune cell infiltration. Hence, further studies on the immune microenvironment of EGFR-mutant lung adenocarcinoma were of great significance for improving the efficacy of immunotherapy in EGFR-mutant lung adenocarcinoma patients in the future. more...

Royal jelly is a yellowish, creamy and acidic substance secreted by mandibular and hypopharyngeal glands of young worker bees. Fatty acids including (E)-10-hydroxy-2-decenoic acid, 10-hydroxydecanoic acid, 3,10-dihydroxydecanoic acid, 8-hydroxyoctanoic acid, sebacic acid and so on are one of the major components of royal jelly with a variety of biological activities, such as anti-inflammation, anti-bacteria and anti-tumor. Fatty acids are one of the main active components of royal jelly which are considered an important indicator in quality control. This article summarizes the identification methods of the royal jelly fatty acid including the principle of the method, the comparisons of technology and application features of methods, as well as the future research prospects. This review will provide a reference for the development of determining methods for fatty acids and pave the way for quality control of royal jelly. more...

BackgroundDibutyl phthalate (DBP) is a common plasticizer in daily life and has been proved to be related to the exacerbation of allergic asthma. Domestic and foreign studies have shown that lipid peroxidation is closely related to the severity of asthma, which can be used as a basis for the diagnosis and treatment of asthma. Whether DBP can induce lipid peroxidation in allergic asthma remains to be further studied.ObjectiveTo investigate whether DBP aggravates allergic asthma by inducing lipid peroxidation in allergic asthma mice.MethodsEighty male BALB/c mice were randomly divided into 4 groups, namely control group, DBP group (40 mg·kg−1), 50 μg ovalbumin (OVA) group (allergic asthma model group), and DBP+OVA group. The DBP group and the DBP+OVA group were given DBP by gavage from Day 1 to 28, and the OVA group and the DBP+OVA group were sensitized by intraperitoneal injection of OVA, once every 3 d, a total of 5 injections, from Day 9 to 21. From Day 29 to 35, the OVA group and the DBP+OVA group were challenged by OVA atomization. After the exposure, samples of blood and lung were collected. The airway hyperresponsiveness of mice was observed by lung function analysis. The serum contents of immunoglobulin E (IgE), OVA-specific immunoglobulin E (OVA-IgE), and lung homogenate levels of interleukin 4 (IL-4) were detected by enzyme-linked immunosorbent assay (ELISA) to evaluate airway allergic inflammation. The pathological changes of lung tissues were observed after hematoxylin-eosin (HE) staining and collagen fiber (Masson) staining. The contents of reactive oxygen species (ROS), lipid ROS, glutathione peroxidase 4 (GPX4), reduced glutathione (GSH), malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) in lung homogenates were detected by ELISA to evaluate lipid peroxidation.ResultsThe results of lung function analysis showed that compared with the control group, the inspiratory resistance (Ri) and expiratory resistance (Re) of the OVA group and the DBP+OVA group were increased, and the lung compliance (Cldyn) was decreased. The DBP + OVA group was more severe, and the difference between the OVA group and the DBP + OVA group was statistically significant (P more...

【Objective】The research aims to investigate the effects of nitrogen application rates on growth, yield, output value and quality of cigar in order to provide a basis for rational application of nitrogen fertilizer in cigar filler planting in Shifang, Sichuan Province.【Method】With Dexue 3 (cigar filler) as material, the variation characteristics of agronomic characters, yield, output value, physical quality and chemical composition of tobacco plants under different nitrogen application rates (0, 60, 120, 150, 180 and 240 kg/hm2, which were recorded as N0, N60, N120, N150, N180 and N240, respectively) were analyzed by field experiment.【Result】Nitrogen application rate had little effect on agronomic character indexes of cigar at topping stage (44 days after transplanting). With the increase of nitrogen application rate, the yield and output value of tobacco leaves increased rapidly at first, then the yield increased slowly, and the output value decreased instead of increasing. Compared with N0 treatment, the yield and output value of nitrogen treatment obviously increased by 11.62%-57.62% and 10.11%-45.83%, respectively. Among them, the highest yield of tobacco leaves under N240 treatment was 2 737.18 kg/hm2, while the highest output value of tobacco leaves under N180 treatment was 99 834.63 yuan/hm2, both higher than those under N150 treatment, but there was no significant difference between treatments. With the increase of nitrogen application rate, the proportion of high-quality grade 1 and grade 2 tobacco leaves increased first and then decreased, while the proportion of lowquality grade 3 and lowest grade tobacco leaves presented an opposite trend, among which grade 1 and grade 2 tobacco leaves under N120 and N150 treatments accounted for the largest proportion, both reaching more than 80%. The comprehensive scores of physical quality and chemical composition of cigar leaves increased first and then decreased with the increase of nitrogen application rate. Among them, the coordination of physical quality and chemical composition of tobacco leaves treated with N120 was relatively better, and the comprehensive scores of physical quality and chemical composition of tobacco leaves were the highest, which were 8.58 and 7.58, respectively,【Conclusion】Suitable nitrogen application rate can increase the yield and output value of cigar tobacco, increase the proportion of high-quality tobacco, improve the physical quality of tobacco, and coordinate the chemical composition. Considering the yield, output value and quality of tobacco leaves, the reasonable nitrogen application rate of cigar filler in Shifang of Sichuan Province is 120-150 kg/hm2. more...

【Objective】Digital economy has a profound impact on China's economic development and can accelerate the process of agricultural modernization. The research theoretically explores how the digital economy drives agricultural modernization, constructs a comprehensive evaluation index system of digital economy and agricultural modernization, analyzes the impact of digital economy on agricultural modernization from a national perspective, and puts forward relevant policy recommendations.【Method】Based on the panel data of 31 provinces (cities, autonomous regions) in China from 2011 to 2020, the levels of digital economy and agricultural modernization were calculated respectively, the internal mechanism of the impact of digital economy on agricultural modernization was analyzed, and the heterogeneity and sub-test of digital economy on agricultural modernization were empirically tested.【Result】(1) Digital economy can drive agricultural modernization; (2) Digital economy can indirectly promote agricultural modernization through labor transfer and human capital investment of farmers; (3) In terms of various dimensions of agricultural modernization, digital economy can promote agricultural production modernization, agricultural modernization output and sustainable development of agricultural modernization, however, its impact on agricultural management modernization is not obvious; (4) Focusing on the development of agricultural modernization in various regions, compared with the eastern and central regions, the western regions have gained higher dividends through digital economy.【Conclusion】The digital economy has shown obvious differences in the process of deepening agricultural modernization in various regions of the whole country. On the basis of the existing achievements in the development and construction of the digital economy, we should continue to promote digital technology to empower agriculture, improve the quality of agricultural talents, deepen the concept of green and organic agriculture, develop digital management strategies in the operation and management of the digital economy that has not yet reflected the achievements, widely adopt e-commerce and online marketing models, push the branding, industrialized and scaled development of agricultural products according to local conditions and local characteristics, deepen the influence of digital economy on agricultural operation and management, and improve the internal mechanism of digital economy to drive agricultural modernization. In addition, the government should adopt different policies according to the development degree of agricultural modernization in different regions, and implement a differentiated and stepwise development strategy. more...