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Background: m6A modification has close connection with the occurrence, development, and prognosis of tumors. This study aimed to explore the roles of m6A modification and its related mechanisms in non-small cell lung cancer (NSCLC). Methods: NSCLC tissues and their corresponding para-cancerous tissues were collected to determine the m6A levels of total RNA/lncRNAs and the expression of m6A modification-related genes/lncRNAs. Then, A549 cells were transfected with si-METTL14 or oe-METTL14, and the cell transfection efficiency was assessed. Subsequently, the viability, apoptosis, cell colony formation, migration and invasion of the different cells were determined. Finally, the nude mouse tumorigenicity experiments were performed to observe the effects of METTL14 in vivo. Results: Compared to the para-NSCLC tissues, the m6A level and METTL14 expression were both significantly increased in the NSCLC tissues (P < 0.05). Based on the expression of METTL14 in the different cell lines, A549 cells were chosen for further experiments. Then, the A549 cells with METTL14 knockdown and overexpression were successfully established, as well as it was found that METTL14 knockdown could inhibit the viability, colony formation, migration, and invasion of A549 cells, while facilitate their apoptosis. In vivo experiments also showed that METTL14 knockdown could inhibit tumor formation and growth. Additionally, the m6A level of MSTRG.292666.16 was higher in the NSCLC tissues; and after METTL14 knockdown, the expression and m6A level of MSTRG.292666.16 were both significantly reduced in A549 cells, and vice versa. Conclusion: METTL14 may promote the progression of NSCLC through up-regulating MSTRG.292666.16 and enhance its m6A modification level. [ABSTRACT FROM AUTHOR]

Background: Osimertinib resistance limits the treatment of epidermal growth factor receptor-(EGFR)-mutated non-small-cell lung carcinoma (NSCLC). The mechanisms of osimertinib resistance need to be elucidated to determine alternative treatment strategies. This study explores the role of M2 type tumor-associated macrophage (TAM)-derived exosomal MSTRG.292666.16 in osimertinib resistance, and its related competing endogenous RNA (ceRNA) mechanism. Methods: M2 type TAMs were induced with 200 ng/mL phorbol 12-myristate 13-acetate, 20 ng/mL IL-4 and IL-13, and M2 type macrophage markers were measured by RT-qPCR. Next, the exosomes were isolated and characterized. Tumor formation in nude mice was conducted using H1975 cells under different treatment conditions. Small RNA sequencing was performed on exosomes derived from sensitive and resistant plasma, and ceRNA networks were constructed. Fluorescence in situ hybridization was used to observe the localization of MSTRG.292666.16, and a ceRNA network (MSTRG.292666.16-miR-6836-5p-MAPK8IP3) was selected for further validation. Results: M2 type TAMs, and M2 type TAM-derived exosomes were successfully induced and isolated. Nude mice results showed that M2 type TAM-derived exosomes and MSTRG.292666.16 overexpression significantly increased tumor volume after administration of osimertinib for 4 weeks. M2 type TAMs were found in the resistant plasma, and MSTRG.292666.16 localized in the cytoplasm of H1975 cells. In addition, the genes in the ceRNA networks were significantly enriched in eight GO terms and seven KEGG pathways, including the MAPK signaling pathway. Subsequently, the levels of MSTRG.292666.16 and MAPK8IP3 significantly increased in both resistant plasma-derived exosomes and M2 type TAM-derived exosomes, while miR-6836-5p levels were significantly reduced. Finally, MSTRG.292666.16, miR-6836-5p, and MAPK8IP3 were part of the same network. Conclusions: M2 type TAM-derived exosomes promoted osimertinib resistance in NSCLC by regulating the MSTRG.292666.16/miR-6386-5p/MAPK8IP3 axis. [ABSTRACT FROM AUTHOR]

Atomically thin monolayer (ML) GeSb 2 Te 4 (GST) holds promising prospects in non-volatile memory applications because of its high non-homogeneous crystallization rate. In GST-based devices, the interaction between GST and metals is crucial, as it affects the electronic properties. Herein, based on first-principles calculations, we investigate the interaction and Schottky barrier height of contacts formed by the combination of ML GST with various metals. It is found that the interfaces of GST with Pt, Pd, Ir and W exhibit strong interaction, characterized by large binding energies ranging from 1.394 to 1.015 eV , and the interfaces between GST and Cu, Ag and Au display weak interaction. For the seven contacts, Ag and W form Ohmic contacts with ML GST, while Cu, Au, Pd, Ir, and Pt form n-type Schottky contacts, with Schottky barrier heights ranging from 0.029 to 0.353 eV . The strong Fermi level pinning at GST-metal interface is observed with a pinning factor of 0.378. Additionally, altering the interfacial distance and optimizing the layers of GST enable a transition from Ohmic contact to Schottky contact. These findings provide crucial guidance for the design and optimization of electronic devices based on phase change materials like GST. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: To determine the prevalence, severity, risk factors and self-perception of female urinary incontinence (UI) in rural Fujian, China. Methods: This population-based cross-sectional study was conducted between June and October 2022. Women aged 20 to 70 years from rural communities in Fujian Province were selected by multistage random sampling. Data from respondents were collected by completing standardised questionnaires through face-to-face interviews. The main outcome was prevalence and self-perception of UI. Results: A total of 5659 valid questionnaires were collected. The overall prevalence of female UI was 23.6% (95% CI 22.5–24.7). The most common type was stress UI with a prevalence of 14.0% (95% CI 13.1–14.9), followed by mixed UI with a prevalence of 6.1% (95% CI 5.5–6.7), and finally urgency UI with a prevalence of 3.5% (95% CI 3.0–3.9). Multivariate regression analysis suggested that older age, obesity, postmenopausal status, multiple vaginal deliveries, macrosomia, instrumental vaginal delivery and previous pelvic floor surgeries were independently associated with UI (P < 0.05). The overall awareness rate of UI was 24.7%, and older age, lower level of education, and income were significantly associated with a decrease in awareness (P < 0.05). Only 33.3% of respondents believed they should seek medical help for UI. Conclusion: UI affects more than one-fifth of women in rural Fujian, and several factors are thought to be associated with its development. Rural women have a poor self-perception of UI, which is exacerbated by older age, lower levels of education, and lower income. [ABSTRACT FROM AUTHOR]

Sulfonylurea (SU) herbicides are widely used and often detected in environmental matrices and have toxic effects on ecosystems and plant development. However, the interaction between SU and soil-plant metabolism during the whole wheat growth cycle remains poorly investigated. Field trials demonstrated that bensulfuron methyl exposure reduced wheat height and a thousand grains' weight, disrupting the critical metabolic pathways, including linoleic acid and amino acid metabolism in the maturity stage. During different growth processes, bensulfuron methyl exposure decreases wheat soil and plants' defense-related indole alkaloid compounds, such as benzoxazinoids and melatonin. Microbial sequencing results showed that bensulfuron methyl treated decreased the abundance of beneficial microorganisms (Gammaproteobacteria , Bacteroidia , and Blastocatella) in the rhizosphere soil, which positively correlated with the inhibition of soil enzyme activity and the secretion of allelopathic substances (benzoxazinoids and melatonin). Molecular docking further confirmed that bensulfuron methyl affects protein molecular structure by establishing hydrogen bonds, which disequilibrate wheat benzoxazinoids and melatonin metabolism. Therefore, bensulfuron methyl exposure disrupted the interaction between soil microorganisms and indole alkaloid metabolism, hindering plant development. This study provides constructive insights into the environmental risks of herbicides and agricultural product safety throughout wheat development. [Display omitted] • Bensulfuron methyl exposure reduces wheat height and a thousand grains' weight. • Bensulfuron methyl lowers wheat plant defense-related indole alkaloid chemicals. • Reducing metabolite secretion and microbe's richness disturb plant-soil signaling conduction. • Bensulfuron methyl occupies the binding site of nutritional and defense proteins. [ABSTRACT FROM AUTHOR]

Isobavachalcone, a naturally occurring chalcone in Psoralea corylifolia , posses many biological properties including anticancer, antiplatelet, and antifungal. However, its glucuronidation, glucuronides excretion, and drug-drug interaction (DDI) involving in human cytochrome P450 (CYP), UDP-glucuronosyltransferase (UGT) enzymes, and efflux transporters (BCRP and MRPs) remains unclear so far. After incubation, three glucuronides were produced by HLM and HIM with total intrinsic clearance (CL int) of 236.71 and 323.40 μL/min/mg, respectively. Reaction phenotyping proved UGT1A1, 1A3, 1A7, 1A8, and 1A9 played important roles in glucuronidation with total CL int values of 62.69–143.00 μL/min/mg. Activity correlation analysis indicated UGT1A1 and UGT1A3 participated more in the glucuronidation. In addition, the glucuronidation showed marked species differences, and rabbits and dogs were probably appropriate model animals to investigate the in vivo glucuronidation. Furthermore, BCRP, MRP1, and MRP4 transporters were identified as the most important contributors to glucuronides excretion in HeLa1A1 cells based on gene silencing method. Moreover, isobavachalcone demonstrated broad-spectrum inhibitory effects against CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, UGT1A1, UGT1A9, UGT2B7 with IC 50 values of 1.08–9.78 μM. Except CYP2B6 and CYP2D6, the calculated [I]/ K i values for other enzymes were all greater than 0.1, indicating the inhibition of systemic metabolism or elimination for these enzyme substrates seems likely. Taken together, we summarized metabolic fates of isobavachalcone including glucuronidation and efflux transport as well as inhibitory effects involving in human CYP and UGT enzymes. [ABSTRACT FROM AUTHOR]

Boswellic acids (BAs), as the main components of frankincense, exhibit notable anti-inflammatory properties. However, their pharmaceutical development has been severely limited by their poor oral bioavailability. Traditional Chinese medicinal processing, called Pao Zhi, is believed to improve bioavailability, yet the mechanism is still completely unclear. Previous research suggested that the bioavailability of a drug can be influenced by physical properties. This paper was designed to investigate the physical properties of frankincense and processed frankincense, including the surface morphology, particle size, polydispersity index (PDI), zeta potential (ZP), specific surface area, porosity, and viscosity. The differences in the intestinal absorption characteristics and equilibrium solubilities between frankincense and processed frankincense were determined by an ultra-high-performance liquid chromatography coupled with a triple quadrupole electrospray tandem mass spectrometry (UHPLC-TQ-MS) analysis method. The results showed that vinegar processing can alter the surface morphology, decrease the particle size and PDI, raise the absolute values of the ZP, specific surface area and porosity, and drop the viscosity of frankincense. Meanwhile, the rates of absorption and dissolution of the main BAs were increased after the processing of frankincense. The present study proves that the physical properties were changed after processing, in which case the bioavailability of frankincense was enhanced. [ABSTRACT FROM AUTHOR]