Lung cancer seriously threatens human health. To explore the molecular mechanism of 20(S)-Protopanaxadiol (PPD) on human non-small cell lung cancer cells, we investigated the transcriptional profile ...of PPD-treated NCI-H1299 cells. Cell proliferation, cell cycle, and apoptosis were detected using cell counting kit-8 and flow cytometry, respectively. Differentially expressed genes (DEGs) between PPD-treated and untreated cells were determined using RNA sequencing and bioinformatic analysis. Protein phosphorylation was detected using Western blotting. Data of mRNA expression profiles of lung cancer were from The Cancer Genome Atlas (TCGA) and analyzed using R software version 4.3.1. PPD showed an inhibitory effect on the proliferation of NCI-H1299 cells and induced apoptosis. There were 938 upregulated genes and 466 downregulated genes in PPD-treated cells, and DEGs were primarily enriched in the MAPK signaling pathway. The detection of phosphorylation revealed that the phosphorylation of ERK and p38 MAPK was significantly reduced in PPD-treated cells. Further comparison of PPD-regulated DEGs with clinical data of lung adenocarcinoma demonstrated that most downregulated genes in tumor tissues were upregulated in PPD-treated cells or vice versa. Two PPD-downregulated genes
and
were associated with patients' overall survival. Therefore, PPD could inhibit NCI-H1299 cells by affecting gene expression and regulating ERK and p38 MAPK pathways.
The mevalonate pathway is known for the synthesis of cholesterol, but recent studies have reported that it also controls Hippo signaling, which is critical for the regulation of organ size and ...tumorigenesis. Here, we discover that the suppression of the mevalonate pathway inhibits the growth and proliferation of colon cancer cell lines. The results of transcriptomic and proteomic assays suggested that the mevalonate pathway controls multiple signaling pathways relevant to cell proliferation, and the results were further confirmed using western blot, PCR, and immunofluorescence assays. As cell proliferation is an energy-consuming process, we postulate that the mevalonate pathway may also control nutrient uptake to coordinate the processes of energy supply and cell proliferation. Here, we found that lovastatin, a mevalonate pathway inhibitor, suppresses glucose and amino acid uptake and lactate acid production. More importantly, mevalonic acid itself is sufficient to promote glucose uptake by colon cancer cells. In addition, we found that colon cancer tissues displayed a higher expression of mevalonate pathway enzymes, which may promote cell growth and stimulate energy uptake. Together, our findings establish the mevalonate pathway as a critical regulator in coordinating energy input and cell proliferation.
This paper proposes an innovative hydrogen-fed high-efficiency X-type rotary engine (XRE) hybrid system by combining with recuperative organic Rankine cycle (RORC). The off-design model is ...established based on optimal thermo-economic parameters. Furthermore, the effects of key operation parameters on system off-design performance are revealed. Two novel ignition advance angle - crankshaft rotational speed (IAA-CRS) and equivalence ratio - crankshaft rotational speed (ER-CRS) control strategies are proposed by adjusting dual-variables. Meanwhile, the modified sliding pressure control strategy is adopted for RORC to obtain constant final XRE exhaust temperature. Finally, the part-load performance superiorities of novel strategies are revealed. The results show that the novel hybrid system thermal efficiency and LCOE could be improved by 24.2% and declined by 22.2% comparing with standalone XRE, respectively. Compared with crankshaft rotational speed and ignition advance angle, XRE peak cylinder gas temperature and pressure are the most sensitive to equivalence ratio. With decreasing XRE load, the optimal ignition advance angle drops firstly and then keeps constant under IAA-CRS strategy, while the optimal equivalence ratio of ER-CRS strategy drops. The novel ER-CRS strategy is the optimal control strategy, which could perform 2.06% and 7.95% higher thermal efficiency than IAA-CRS and traditional CRS strategies at most.
•Hydrogen-fed XRE hybrid system by coupling with RORC using dual operation modes.•0-D off-design model is established based on optimal thermo-economic parameters.•Crankshaft rotational speed, ignition advance angle, equivalence ratio are studied.•Novel IAA-CRS and ER-CRS strategies by adjusting dual variables are proposed.•Part-load performance advantages of novel control strategies are revealed.
Herbal medicines have played a vital role in maintaining the health of the world population in the past thousands of years, and have proved to be an effective therapy. It is important to improve our ...understanding of the effects of the multi-step processing in herbal medicines on the chemical changes to ensure product quality. A proton nuclear paramagnetic resonance (
H NMR)-based evaluation strategy was developed for an efficient process variation exploration and diversified metabolite identification. In this study, 48 process intermediates from 6 commercial batches of the multi-step manufacturing chain of Danshen processing were obtained. Hierarchical classification analysis (HCA) tree based on
H NMR spectra clustered the samples according to the processing steps, which indicates that
H NMR has the potential capability for critical control point identification based on its adequate information of the organic compounds. Then, principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were applied to distinguish the major metabolite differences between the intermediates before and after the critical control point. In this case, the alkali-isolation and acid-dissolution method was recognized as the most critical process in the multi-step chain of Danshen extract manufacturing. Potential metabolites with the larger amplitude of variation and contributing the most to the discrimination were found to be potential quality markers by
-plot, including several previously undetected amino acids. The results in this study are consistent with previous research studies and reference experiments conducted with other analytical tools. Taken together, they prove that
H NMR with chemometrics is a very effective process quality control tool to provide comprehensive information on the chemical changes during the processing of herbal medicines, and help with the identification of critical control points and potential critical quality markers.
Based on non-collinear phase-matching (PM), a new method for widely tunable wavelength was proposed and demonstrated in a four-mirror ring cavity of non-critical phase-matching (NCPM) KTiOAsO
4
(KTA) ...optical parametric oscillator (OPO). Wavelength tuning range of 141 nm from 1535.56 nm to 1676.73 nm was achieved by moving one mirror of ring cavity back and forth. The tuning theory and tuning method of non-collinear PM were analyzed in detail. The output energy and pulse width of signal were measured and compared in collinear and non-collinear PM condition. This method is also applicable to OPOs of other nonlinear crystals based on four-mirror ring cavity.
Autophagy has been proved to play a vital role in cardiac hypertrophy. The present study was designed to investigate the relationship between miR-100-5p and autophagy in the development of cardiac ...hypertrophy. Here, miR-100-5p expression was detected in abdominal aortic coarctation (AAC)-induced cardiac hypertrophy rats and Angiotensin II (Ang II)-stimulated cardiomyocytes. In vitro and in vivo experiments were performed to explore the function of miR-100-5p on autophagy and cardiac hypertrophy. We also investigated the mechanism of miR-100-5p on autophagy with dual-luciferase reporter assays, RNA immunoprecipitation (RIP), quantitative real-time PCR (qRT-PCR), western blot, immunofluorescence, and transmission electron microscopy (TEM). The results showed that miR-100-5p was highly expressed in hypertrophic hearts and Ang II-induced cardiomyocytes. Overexpression of miR-100-5p promoted the expression of cardiac hypertrophy markers ANP, BNP and β-MHC and cell surface area, while those were suppressed by miR-100-5p inhibitor. Knockdown of miR-100-5p by antagomiR significantly improves cardiac function and attenuate cardiac hypertrophy in vivo. Mechanistic investigation has found that miR-100-5p promote autophagy by targeting mTOR. Inhibition of autophagy by 3-methyladenine (3-MA) or mTOR overexpression could reverse the function of miR-100-5p in cardiac hypertrophy. These results elucidate that miR-100-5p promoted the pathogenesis of cardiac hypertrophy through autophagy activation by targeting mTOR.
The complete genome of Cordyceps militaris was sequenced using single-molecule real-time (SMRT) sequencing technology at a coverage over 300×. The genome size was 32.57 Mb, and 14 contigs ranging ...from 0.35 to 4.58 Mb with an N50 of 2.86 Mb were assembled, including 4 contigs with telomeric sequences on both ends and an additional 8 contigs with telomeric sequences on either the 5' or 3' end. A methylome database of the genome was constructed using SMRT and m4C and m6A methylated nucleotides, and many unknown modification types were identified. The major m6A methylation motif is GA and GGAG, and the major m4C methylation motif is GC or CG/GC. In the C. militaris genome DNA, there were four types of methylated nucleotides that we confirmed using high-resolution LCMS-IT-TOF. Using PacBio Iso-Seq, a total of 31,133 complete cDNA sequences were obtained in the fruiting body. The conserved domains of the nontranscribed regions of the genome include TATA boxes, which are the initial regions of genome replication. There were 406 structural variants between the HN and CM01 strains, and there were 1,114 structural variants between the HN and ATCC strains.
Urban green space has a cooling effect and its cooling effect can extend to the surrounding environment, conspicuously decreasing with distance. Land surface temperature (LST) and cooling distance ...are generally researched based on remote sensing and temperature inversion algorithms; this distance is affected by internal and external environment factors, but the high-intensity cooling distance (HCD) is overlooked by using large scale datasets. In addition, the comprehensive relationship between internal and external factors with cooling distance and HCD is still unclear. The aim of this study is to identify the HCD of green spaces by monitoring the changes of LST away from it and to quantify the influences of 12 internal and external factors on HCD. A multiple linear regression model is used to analyze the relationship between them. In the summer of 2022, we measured and calculated HCD for 59 urban green spaces in Xi’an, China. The analysis results show that the HCD is not only affected by the internal landscape factors of green spaces, but also closely related to factors associated with the natural environmental, urban attributes, and surrounding structures. These findings can rationally assist the planning of the allocation of urban green spaces and provide a scientific basis for mitigating the urban heat island effect.
Real-time topology estimation in distribution grid with high penetration of distributed energy resources remains a challenging task due to the insufficient high-precision measurements and frequent ...topology variations. This article proposes a real-time distribution system topology estimation approach building on the graph theory and Bayesian networks with sparse measurements. The graph theory develops the topology graph bank to effectively leverage the prior knowledge of topology models, including the topology structure and the switching relationship between different topologies. This allows the development of the Bayesian networks for topology tracking using real-time voltage and power injection measurements. A novel discrete method considering the similarity of data correlation information is proposed for the optimal placement of μ PMUs to ensure the performance of topology estimation. Numerical results on the IEEE 33-node and 123-node systems show that the BN-based topology estimation model has better performance against incomplete information, i.e., missing data, than other alternatives.
Patterned composites with custom-tailored properties are essential for efficient thermal management required by the increasing integration and complexity of devices. In this work, a facile approach ...for the fabrication of functional, robust, and patterned composites was demonstrated using a simple and scalable laser engraving technique. Graphene patterns were incorporated into composites by the single- or multiple-lasing on poly(Ph-ddm) substrate. The resultant composites exhibited a high thermal conductivity (8.2 W/(m·K)) that was equivalent to an enhancement of 45 times compared to pure matrix. This increase was attributed to the formed high-quality graphene porous architecture, which established an effective heat conduction channel. With the merit of computer-aided design of the laser trajectory, the processing method offers the freedom to tailor the heat transfer pathway in composites. Besides, the composites presented the favorable Joule heating performance in terms of fast and stable response with the heating efficiency up to 276 °C‧cm2/W. More interestingly, the heaters with designable thermal patterns were also allowed, in which the electrical property of each heating unit could be tailored by adjusting laser parameters. This provides a unique opportunity to simulate the real case of non-uniform heat sources in many electronic devices, which will facilitate the design and development of heating dissipation systems. The material/process developed promises a wide range of possibilities for the efficient thermal management applications.
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•Patterned functional composites are developed for efficient thermal management using a simple laser engraving technique.•The resultant composites have a high thermal conductivity (8.2 W/(m·K)) that is 45-fold higher than that of neat resin.•The processing method offers the freedom to tailor heat transfer pathways in composites.•Designable heaters are proposed to simulate the real case of non-uniform thermal distribution of electronic components.
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