N-O Reduction and ROS-Mediated AKT/FOXO1 and AKT/P53 Pathways Are Involved in Growth Promotion and Cytotoxicity of Cyadox.

Cyadox is a novel derivative of quinoxaline-1,4-dioxides (QdNOs) with the potential to be developed as a feed additive. However, the pharmacological and toxicological bioactive molecules of cyadox and the molecular mechanism of its pharmacological and toxic actions remain unclear. In the present study, cyadox and its main metabolites of cy1, cy4, cy6, and cy12 were selected; the growth promotion characteristic was indicated by the mRNA level of EGF; and the cytotoxicity of cyadox was determined by methylthiazol tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release, and Annexin V-FITC/PI apoptosis detection kit with flow cytometry. The intracellular ROS, cyclin D1, and Akt/P53/FOXO1 signaling pathway were also investigated. Our data suggested that cyadox showed relatively higher activity than its metabolites, and the ROS was generated from N-O reduction of cyadox. Moreover, cyadox (2 µM) activated the Akt and increased the EGF, cyclin D1, and FOXO1 expression levels. Cyadox (100 µM) induced cytotoxicity in L02 cells in a concentration- and time-dependent manner. Additionally, the activated P53 pathway, hyperactivated Akt, and apoptosis were found in L02 cells after incubation with 100 µM cyadox. Our data demonstrated that Akt promoted cell survival when it was mildly activated by cyadox at 2 µM, and Akt leads to apoptosis when it was severely activated by cyadox at 100 µM. Thus, the present study revealed that N-O reduction of cyadox and ROS-mediated AKT/FOXO1 and AKT/P53 pathways were involved in growth promotion and cytotoxicity of cyadox.

YuPingFeng (YPF) upregulates caveolin-1 (CAV1) to alleviate pulmonary fibrosis through the TGF-ß1/Smad2 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) is considered a valuable asset in China's medical tradition. YPF is a classic prescription that has been derived from the "Jiu Yuan Fang" formula and consists of three herbs: Huangqi (Astragalus membranaceus Bunge), Baizhu (Atractylodes rubra Dekker), and Fangfeng (Saposhnikovia divaricata (Turcz.) Schischk). This prescription is widely acclaimed for its exceptional pharmacological properties, including potent antioxidant effects, hormone regulation, and immune modulation effects. AIM OF THE STUDY: Previous research provides evidence suggesting that YPF may have therapeutic effects on pulmonary fibrosis. Further exploration is essential to confirm its effectiveness and elucidate the fundamental processes. MATERIALS AND METHODS: First, the active components and target genes of YPF were extracted from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Next, the GSE53845 dataset, which contains information on pulmonary fibrosis, was downloaded from the GEO database. Network informatics methods was then be utilized to identify target genes associated with pulmonary fibrosis. A YPF-based network of protein-protein interactions was constructed to pinpoint possible target genes for pulmonary fibrosis treatment. Additionally, an in vitro model of pulmonary fibrosis induced by bleomycin (BLM) was established to further investigate and validate the possible mechanisms underlying the effectiveness of YPF. RESULTS: In this study, a total of 24 active ingredients of YPF, along with 178 target genes associated with the treatment, were identified. Additionally, 615 target genes related to pulmonary fibrosis were identified. Functional enrichment analysis revealed that 18 candidate genes (CGs) exhibited significant responses to tumor necrosis factor, NF-kB survival signaling, and positive regulation of apoptosis processes. Among these CGs, CAV1, VCAM1, and TP63 were identified as key target genes. Furthermore, cell experiments confirmed that the expression of CAV1 protein and RNA expression was increased in pulmonary fibrosis, but significantly decreased after treatment with YPF. Additionally, the expression of pSmad2, α-SMA, TGF-ß1, and TNF-α was also decreased following YPF treatment. CONCLUSIONS: Network pharmacology analysis revealed that YPF exhibits significant potential as a therapeutic intervention for pulmonary fibrosis by targeting various compounds and pathways. This study emphasizes that the efficacy of YPF in treating pulmonary fibrosis may be attributed to its ability to up-regulate CAV1 expression and inhibiting pulmonary fibrosis via modulation of the TGF-ß1/Smad2 signaling pathway. These findings underscore the promising role of YPF and its ability to potentially alleviate pulmonary fibrosis.

Design of H-Shape Chamber in Thermal Bubble Printer.

The utilization rate of ink liquid in the chamber is critical for the thermal bubble inkjet head. The difficult problem faced by the thermal bubble inkjet printing is how to maximize the use of ink in the chamber and increase the printing frequency. In this paper, by adding a flow restrictor and two narrow channels into the chamber, the H-shape flow-limiting structure is formed. At 1.8 µs, the speed of bubble expansion reaches the maximum, and after passing through the narrow channel, the maximum reverse flow rate of ink decreased by 25%. When the vapor bubble disappeared, the ink fills the nozzle slowly. At 20 µs, after passing through the narrow channel, the maximum flow rate of the ink increases by 39%. The inkjet printing frequency is 40 kHz, and the volume of the ink droplet is about 13.1 pL. The structure improves the frequency of thermal bubble inkjet printing and can maximize the use of liquid in the chamber, providing a reference for cell printing, 3D printing, bioprinting, and other fields.

Bismuth fire assay preconcentration and empirical coefficient LA-ICP-MS for the determination of ultra-trace Pt and Pd in geochemical samples.

In this work, a novel method of solid sample pretreatment technique of bismuth fire assay (Bi-FA) combined with solid sample determination by laser ablation ICP-MS (LA-ICP-MS) was reported for the determination of ultra-trace Pt and Pd in geochemical samples. Bismuth oxide (Bi2O3) was used as fire assay collector to directly enrich Pt and Pd from solid samples, and Ag protection cupellation was employed to generate Ag granules. After cleaning, weighing and annealing, the Ag granules were compressed into thin slices and determined by LA-ICP-MS for 195Pt, 105Pd and 109Ag (109Ag was selected as the internal standard isotope). Bi2O3 provided exceptionally low blanks compared to nickel oxide and lead oxide commonly employed in fire assay procedures, and could be applied directly without purification. Different from traditional empirical coefficient method, the Chinese Certified Reference Materials (CRMs) for Pt and Pd were treated by the same procedure to obtain completely matrix matched Ag slices. And then modified empirical coefficient method and internal standard calibration strategy was used to reduce the instability of LA-ICP-MS, and random multipoint laser ablation was employed to further reduce analytical variation resulting from heterogeneity of Pt and Pd in the Ag slice. Under optimal conditions, excellent calibration curves for Pt and Pd were obtained (0.407-2958 µg g-1 and 0.407-2636 µg g-1, respectively), with correlation coefficients exceeding 0.9996. The method detection limits for Pt and Pd were 0.074 and 0.037 ng g-1, respectively. The established method was applied successfully to analysis of real geochemical samples, with determined values in good agreement with the results of traditional Pb-FA graphite furnace atomic absorption spectrometry (GF-AAS), and spiked recoveries between 87.8 and 125.0%.

Design of Chopsticks-Shaped Heating Resistors for a Thermal Inkjet: Based on TaN Film.

Efficient printing frequency is critical for thermal bubble inkjet printing, while the difficulty lies in the structural design and material selection of the heating resistors. In this paper, a TaN film was used as the main material of the heating resistors, and two TaN films were placed in parallel to form the chopsticks-shaped structure. The heating time was divided into two sections, in which 0-0.1 µs was the preheating and 1.2-1.8 µs was the primary heating. At 1.8 µs, the maximum temperature of the Si3N4 film could reach about 1100 °C. At the same time, the SiO2 film was added between the TaN film and Si3N4 film as a buffer layer, which effectively avoided the rupture of the Si3N4 film due to excessive thermal stress. Inside the inkjet print head, the maximum temperature of the chamber reached about 680 °C at 2.5 µs. Due to the high power of the heating resistors, the working time was greatly reduced and the frequency of the inkjet printing was effectively increased. At the interface between the back of the chip and the cartridge, the SiO2 film was used to connect to ensure a timely ink supply. Under the condition of 12 V at 40 kHz, the inkjet chip could print efficiently with 10 nozzles at the same time. The inkjet chip proposed in this paper is not limited to only office printing, but also provides a new reference for 3D printing, cell printing, and vegetable and fruit printing.

CUX1, A Controversial Player in Tumor Development.

CUX1 belongs to the homeodomain transcription factor family and is evolutionarily and functionally conserved from Drosophila to humans. In addition to the involvement in various physiological events including tissue development, cell proliferation, differentiation and migration, and DNA damage response, CUX1 has been implicated in tumorigenesis. Interestingly, CUX1 has been recently recognized as a haploinsufficient tumor suppressor, which is paradoxically overexpressed in tumor cells. While loss of heterozygosity and/or mutations of CUX1 have been frequently detected in many types of cancers, genomic amplification, and overexpression of CUX1 have also been reported in cancer tissues and are correlated with higher tumor grade and poor prognosis. Therefore, deciphering the roles of different CUX1 isoforms and in different tumor stages is required to establish a CUX1-based therapeutic strategy for cancer treatment.