Pseudolaric acid B suppresses NSCLC progression through the ROS/AMPK/mTOR/autophagy signalling pathway.

Pseudolaric acid B (PAB), an acid isolated from the roots of Pseudolarix kaempferi gorden, has shown antitumour effects through multiple mechanisms of action. The objective of this study was to investigate the anticancer effect of PAB on non-small cell lung cancer (NSCLC) and its underlying mechanism. In our experiments, we observed that PAB decreased cell viability, inhibited colony formation, induced cell cycle arrest, impeded scratch healing, and increased apoptosis in H1975 and H1650 cells. Additionally, PAB treatment enhanced the fluorescence intensity of MDC staining in NSCLC cells, upregulated the protein expression of microtubule-associated protein light chain 3 II (LC3 II), and downregulated the expression of sequestosome 1 (SQSTM1/P62). Combined treatment with PAB and chloroquine (CQ) increased the protein expression levels of LC3 II and P62 while decreasing the apoptosis of H1975 and H1650 cells. Moreover, treatment with PAB led to significant mTOR inhibition and AMPK activation. PAB combined with compound C (CC) inhibited autophagy and apoptosis. Furthermore, PAB treatment increased intracellular reactive oxygen species (ROS) levels in NSCLC cells, which correlated with the modulation of the AMPK/mTOR signalling pathway and was associated with autophagy and apoptosis. Finally, we validated the antitumour growth activity and mechanism of PAB in vivo using athymic nude mice bearing H1975 tumour cells. In conclusion, our findings suggest that PAB can induce apoptosis and autophagic cell death in NSCLC through the ROS-triggered AMPK/mTOR signalling pathway, making it a promising candidate for future NSCLC treatment.

Gut microbiota and its metabolic products in acute respiratory distress syndrome.

The prevalence rate of acute respiratory distress syndrome (ARDS) is estimated at approximately 10% in critically ill patients worldwide, with the mortality rate ranging from 17% to 39%. Currently, ARDS mortality is usually higher in patients with COVID-19, giving another challenge for ARDS treatment. However, the treatment efficacy for ARDS is far from satisfactory. The relationship between the gut microbiota and ARDS has been substantiated by relevant scientific studies. ARDS not only changes the distribution of gut microbiota, but also influences intestinal mucosal barrier through the alteration of gut microbiota. The modulation of gut microbiota can impact the onset and progression of ARDS by triggering dysfunctions in inflammatory response and immune cells, oxidative stress, cell apoptosis, autophagy, pyroptosis, and ferroptosis mechanisms. Meanwhile, ARDS may also influence the distribution of metabolic products of gut microbiota. In this review, we focus on the impact of ARDS on gut microbiota and how the alteration of gut microbiota further influences the immune function, cellular functions and related signaling pathways during ARDS. The roles of gut microbiota-derived metabolites in the development and occurrence of ARDS are also discussed.

The EMT-Related Genes GALNT3 and OAS1 are Associated with Immune Cell Infiltration and Poor Prognosis in Lung Adenocarcinoma.

BACKGROUND: Lung cancer is the main cause of cancer-related death, with epithelial-mesenchymal transition (EMT) playing an important role in the development of this disease. The EMT-related genes Polypeptide N-Acetylgalactosaminyltransferase 3 (GALNT3) and 2'-5'-Oligoadenylate Synthetase 1 (OAS1) are involved in numerous tumor processes. Although these genes have been extensively studied in cancer, they have yet to be analyzed by multi-omics in lung adenocarcinoma (LUAD). METHODS: EMT-related genes were identified by R and Venn diagram. Cox regression and Kaplan-Meier analysis were performed to evaluate patient survival, and the Gene Expression Profiling Interactive Analysis (GEPIA) database was used for correlation analysis. GeneCards and R packages were used to explore gene characterization and functional annotation. The Tumor Immune Estimation Resource (TIMER), Human Protein Atlas (HPA), University of Alabama at Birmingham Cancer (UALCAN), and The Cancer Genome Atlas (TCGA) databases were used to investigate gene expression, which was then confirmed by RT-PCR. Clinicopathological analysis was carried out using the UALCAN database. Functional mechanisms and multi-omics analysis were performed using DNA Methylation Interactive Visualization Database (DNMIVD), Targetscan, TIMER, Tumor-immune System Interactions Database (TISIDB) and cBioportal. Diagnostic values were calculated using ROC curve analysis. RESULTS: A total of 320 EMT-related genes were identified in LUAD. Their characteristics were confirmed in the Database for Annotation, Visualization and Integrated Discovery (DAVID) database by the intersection of 855 and 3600 different genes from the Gene Expression Omnibus (GEO) and EMTome databases, respectively. Expression of the EMT-related genes GALNT3 and OAS1 was associated with the prognosis of LUAD patients. A positive correlation was observed between the expression of GALNT3 and OAS1, and their expression was higher in LUAD tissue than in normal lung tissue. This was confirmed using RT-PCR. Multi-omics analysis revealed that GALNT3 and OAS1 expression was associated with gene mutation and methylation, cellular immune infiltration, and several immune subtypes. A miRNA-GALNT3/OAS1 regulatory network was also found. Receiver operating characteristic (ROC) curve analysis found that GALNT3 and OAS1 expression combined had superior diagnostic value to that of each marker alone. CONCLUSIONS: GALNT3 and OAS1 expression are associated with immune cell infiltration and poor prognosis in LUAD. Their combined expression has high diagnostic value; hence, GALNT3 and OAS1 may be valuable biomarkers for the early detection of LUAD.

Wheat yield and nitrogen use efficiency enhancement through poly(aspartic acid)-coated urea in clay loam soil based on a 5-year field trial.

The innovation of N fertilizer and N management practices is essential to maximize crop yield with fewer N inputs. A long-term field fertilization experiment was established in 2015 on the North China Plain (NCP) to determine the effects of a control treatment (CN) and the eco-friendly material poly(aspartic acid)-coated urea (PN), applied as a one-time basal application method, on winter wheat yield and N use efficiency at four N application rates: 0 (N0), 63 (N63), 125 (N125), and 188 (N188) kg N ha-1. The results indicated that compared to CN, PN resulted in a significant increase in wheat yield by 9.6% and 9.2% at N63 and N125, respectively, across the three experimental years, whereas no significant (p < 0.05) difference was detected at N188. Leaf area duration (LAD), crop growth rate (CGR), and dry matter accumulation (DMA) increased with increasing N rates, while PN significantly increased LAD and CGR by 5.1%-16.4% and 5.4%-64.3%, respectively, during the anthesis-ripening growth stage and DMA by 13.7% and 10.1% at N63 and N125, respectively, after the anthesis stage compared to CN. During the grain-filling stage, PN significantly increased the kernel maximum grain-filling rate (Gmax) by 21.7% and the kernel weight at the maximum grain-filling rate (Wmax) by 6.7% at N125 compared to CN. Additionally, compared to CN, PN significantly improved the stover and grain N content at harvest and increased NUT, NPFP, and NAE by 5.7%-40.1%, 2.5%-23.3%, and 3.9%-42.8%, respectively, at N63-N125. Therefore, PN applied using a single basal nitrogen fertilizer application method showed promising potential in maintaining a stable wheat yield and increasing N use efficiency with a 33% urea cut (approximately 63 kg N ha-1) compared to CN at the current wheat yield level on the NCP.

Effect of Urea Coated with Polyaspartic Acid on the Yield and Nitrogen Use Efficiency of Sorghum (Sorghum bicolor, (L.) Moench.).

Innovative approaches to enhance N fertilization to improve season-long N availability are essential to optimal sorghum (Sorghum bicolor, (L.) Moench.) productivity and N use efficiency. A two-year field experiment was conducted in the 2020 and 2021 summer seasons on the North China Plain to determine the effects of a novel urea coated with polyaspartic acid (PAA) (PN) and a control treatment (CN) on grain sorghum yield and N utilization characteristics at four N application rates (0, 60, 120, and 240 kg ha-1). The results showed that sorghum yield, agronomic traits (including leaf area duration (LAD), crop growth rate (CGR), and dry matter accumulation (DMA)), the accumulation of nitrate N and ammonium N in the 0-60 cm soil layer, stover and grain N content, and total N uptake (NUT) in 2020 and 2021 significantly increased as N application rates increased from 0 to 240 kg ha-1, whereas nitrogen agronomic efficiency (NAE), N uptake efficiency (NUpE), and N utilization efficiency (NUtE) varied inversely with increasing N application rates. Compared to CN, PN demonstrated a significant enhancement in grain sorghum yield, LAD, and CGR, from 3.3% to 7.1%, from 4.8% to 6.1%, and from 5.8% to 6.8%, respectively, at 60 and 120 kg N ha-1. PN improved the N availability (mainly nitrate-N) in the sorghum soft dough and the stover and grain N content at harvest and NUT, NUpE, and NAE accordingly compared with CN at the 60 and 120 kg ha-1 N application rates. In short, our two-year field trials demonstrated that PN with 120 kg N ha-1 is recommended in grain sorghum to optimize sorghum productivity and nitrogen use efficiency at the current yield level in the North China Plain.

[Panax notoginseng saponins inhibit proliferation, migration, invasion and promote apoptosis of U2OS osteosarcoma cells via blocking Notch1 pathway].

Objective To explore the effects of Panax notoginseng saponins (PNS) on the proliferation, apoptosis, migration and invasion of osteosarcoma cell line U2OS and its possible molecular mechanism. Methods Human osteosarcoma cell line U2OS was cultured and treated with (0, 200, 400, 600, 800, 1000) µg/mL PNS. The proliferation of U2OS was detected by CCK-8 method. Annexin V-FITC/PI double labeling combined with flow cytometry was used to analyze cell apoptosis. Clone formation assay was used to detect the clone formation ability of the cells. TranswellTM invasion assay was performed to detect cell invasion. TranswellTM migration assay and wound-healing assay were used to determine cell migration. Western blotting was used to detect the expression of Notch1 and downstream protein Hes1 in U2OS cells. Results Compared with the control group, PNS could inhibit the proliferation of U2OS cells and the formation of clonal plaques, increase cell apoptosis rate, weaken the ability of migration and invasion and decrease the expression levels of Notch1 and Hes1 in the cells in a dose-dependent manner. Conclusion PNS can significantly inhibit the proliferation, migration and invasion and promote cell apoptosis of U2OS cells by blocking Notch1 signaling pathway.

Effects of basic application of chlorocholine chloride combined with nitrogen fertilizer on nitrogen use of summer maize in North China Plain.

To clarify the effects of combined applications of chlorocholine chloride (CCC) and nitrogen fertilizer (CN) on nitrogen metabolism and nitrogen use efficiency of summer maize, we conducted a field experiment in Xinxiang experimental station of Chinese Academy of Agricultural Sciences in 2018 and 2019, with four nitrogen application rates (0, 62.5, 125 and 187.5 kg·hm-2), and two maize varieties of Jingnongke 728 (JNK728) and Zhongdan 909 (ZD909). The results showed that across the two years CN-CCC increased maize yield by 7.7% and 5.0% under the nitrogen application rates of 62.5 kg·hm-2 and 125 kg·hm-2, respectively. CN-CCC increased the contents of nitrate reductase, glutamine synthetase, glutamate synthetase and soluble protein, and finally promoted nitrogen metabolism. Under the low and middle nitrogen application conditions (62.5 kg·hm-2 and 125 kg·hm-2), plant nitrogen content of JNK728 and ZD909 increased by 17.6% and 30.3%, grain nitrogen content increased by 10.3% and 17.4%, nitrogen partial productivity, agronomic efficiency of applied nitrogen, recovery efficiency of applied nitrogen, nitrogen use efficiency increased by 10.0%, 15.7%, 23.3%, 24.8% and 5.7%, 15.0%, 49.9%, 71.7%, respectively. In conclusion, appropriate basic application of CN-CCC could enhance nitrogen metabolism, increase nitrogen use efficiency and grain yield of summer maize. Our results showed that CCC combined basic nitrogen application of 125 kg·hm-2 had the best effect.

Formation of highly luminescent cesium bismuth halide perovskite quantum dots tuned by anion exchange.

Cs3Bi2Br9 quantum dots (QDs) with photoluminescence quantum yields (PLQYs) of up to 22% were prepared through the steady binding of octylammonium bromide and oleic acid. Excellent thermal stability and good luminescence properties have been achieved as intrinsic features of the inorganic halide perovskites, as well as the effective passivation of surface trap-states.