Environmental design as a practical major in the university, is concentrating on training students to become professional designers to fit the requirements of the design market today. Traditional ...design education that only construction documents with CAD technology training has no longer satisfied the needs of economy and the market today, so we have to explore new strategy to change the way of teaching. This article explores some examples of new strategy of how to set up lecture, studio practices, and competition workshop for environmental design course system in high education institute in China. The goal is to transform abstractive thinking in art and design perception to representational diagram in visual technique. We hope this new exploration can reform the atmosphere during studio education, with merging new technique such as new digital media, AI and IT technology, and therefore, change the learning technique and improve students to learn more.
Although first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy is effective for treating EGFR-mutant non-small cell lung cancer (NSCLC), it is now understood that ...drug-tolerant persister (DTP) cells escaping from initial treatment eventually drives drug resistance. Here, through integration of metabolomics and transcriptomics, we found that the neurotransmitter acetylcholine (ACh) was specifically accumulated in DTP cells, and demonstrated that treatment with EGFR-TKI heightened the expression of the rate-limiting enzyme choline acetyltransferase (ChAT) in ACh biosynthesis via YAP mediation. Genetic and pharmacological manipulation of ACh biosynthesis or ACh signaling could predictably regulate the extent of DTP formation in vitro and in vivo. Strikingly, pharmacologically targeting ACh/M3R signaling with an FDA-approved drug, darifenacin, retarded tumor relapse in vivo. Mechanistically, upregulated ACh metabolism mediated drug tolerance in part through activating WNT signaling via ACh muscarinic receptor 3 (M3R). Importantly, we showed that aberrant ACh metabolism in patients with NSCLC played a potential role in predicting EGFR-TKI response rate and progression-free survival. Our study therefore defines a therapeutic strategy--targeting the ACh/M3R/WNT axis--for manipulating EGFR TKI drug tolerance in the treatment of NSCLC.
Gastric cancer (GC) represents a significant burden of cancer-related mortality worldwide, underscoring an urgent need for the development of early detection strategies and precise postoperative ...interventions. However, the identification of non-invasive biomarkers for early diagnosis and patient risk stratification remains underexplored. Here, we conduct a targeted metabolomics analysis of 702 plasma samples from multi-center participants to elucidate the GC metabolic reprogramming. Our machine learning analysis reveals a 10-metabolite GC diagnostic model, which is validated in an external test set with a sensitivity of 0.905, outperforming conventional methods leveraging cancer protein markers (sensitivity < 0.40). Additionally, our machine learning-derived prognostic model demonstrates superior performance to traditional models utilizing clinical parameters and effectively stratifies patients into different risk groups to guide precision interventions. Collectively, our findings reveal the metabolic landscape of GC and identify two distinct biomarker panels that enable early detection and prognosis prediction respectively, thus facilitating precision medicine in GC.
Building Information Modelling(BIM) is the foundation of digital transformation in architecture, engineering, and construction(AEC)industry. BIM is the holistic process of creating and managing ...information for a built asset. A traditional CAD and 3D modelling technology is widely used in university’s architecture and landscape courses teaching today. Every single detail of traditional course education does not match the internationally market and BIM technology which is more common and popular today. Using BIM technology in university to teach architecture and landscape design will make changes to design education, and will improve the education practice in Environmental Design system. This article will introduce more detail about BIM technology, and how it changes and affects traditional architecture & landscape teaching, how this technology merged with professions, and how this technology brings comprehensive learning ways and new insight for students in their future career life.
Inhibitors are an important means of reducing the growth of foodborne microorganisms. However, excessively using inhibitors will cause great harm to human beings and organisms. Therefore, ...quantitatively evaluating the effect of low-dose inhibitors on foodborne bacteria growth is very important. Electrochemical impedance spectroscopy (EIS) is a commonly used biosensor technique for detecting foodborne bacteria. In this paper, we show a machine learning-based EIS biosensor method that can be used to detect the effect of a low-dose inhibitor (e.g., hydrogen peroxide) on Escherichia coli (E. coli). After obtaining the minimum inhibitory concentration (MIC), the inhibitor concentration and below was applied to E. coli solution. EIS data were obtained by binding the target bacteria to the electrode surface through antibodies, and then, the impedance parameters were fitted by the Randles model. XGBoost and a support vector regression (SVR) machine learning models were compared to establish a quantitative relationship between multiple impedance parameters and the bacterial concentration under the effect of inhibitors. The results showed that XGBoost improved the quantitative analysis accuracy toward inhibitors (0.175–0.375 μL/mL), based on the bacteria growth in the solution. After different low concentrations of the inhibitor were added into a standard bacterial solution for 1 h, 2 h and 3 h, the maximum prediction error of the inhibitor concentration was 4.95%, 1.03% and 0.46%, respectively. The prediction error decreased as the incubation time of the E. coli culture was extended. These results pave the way for the automation of an accurate EIS biosensor for analyzing foodborne microorganisms under various low doses of inhibitors or drugs
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
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•Novel R. ruber chaperones were identified by transcriptome analysis.•R. ruber chaperone GroEL2 was distinguished from conventional GroEL.•GroEL2 showed high self-thermal stability ...and protection effect on other proteins.•NHase-GroEL2 fusion chimera enhanced the activity of NHase by 63.6%.•It also enhanced thermal stability by 2.9× and acrylamide resistance by 1.1×.
Rhodococcus ruber harboring intracellular nitrile hydratase (NHase) is widely used in large-scale acrylamide production. Transcriptome analyses of R. ruber under urea induction and heat shock revealed the novel chaperones GroEL2 and GroES. M. jannaschii chaperone rTHS, functional in organic solvent as reported in literature, was selected as control. In vitro experiments (70 °C/90 °C incubation) showed that GroEL2 from R. ruber was highly thermostable and can stabilize other proteins as well. GroEL2 was co-expressed with NHase in E. coli in three ways: (a) monocistronic expression with one T7 promoter, (b) bicistronic expression with double T7 promoters, and (c) fusion expression with one T7 promoter driving the NHase-GroEL2 chimera. Experimental results showed that the NHase-GroEL2 chimera was the most successful expression strategy. Maximal NHase activity was enhanced by 63.6% compared with the single NHase control. A stability assessment showed that the residual activity levels after heat shock and acrylamide (AM) immersion increased by 2.9× and 1.1×, respectively. For the fusion chimeras NHase-GroES and NHase-rTHS, their thermal stability also significantly enhanced by 1.6× and 64.0%, respectively; but their AM resistance both reduced (36.2% and 29.0%, respectively). In vivo heat inactivation curves further confirmed thermal stability enhancement of NHase by chaperone fusion, in which NHase-GroEL2 was the most stable one. Its inactivation constant kd was only ∼1/4 that of the single NHase. The Kcat of the intracellular NHase-GroEL2 was also remarkably higher than that of the NHase control.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK, ZRSKP
Antibiotic detection includes direct detection and indirect detection. Indirect detection of antibiotic concentration reflected by the change of bacterial concentration is a more intuitive evaluation ...of antibiotic effect. It can not only accurately evaluate antibiotics, but also be used for tracking evaluation and analysis of antibacterial effects under long-term low-threshold levels. In this paper, a novel method of electrode modification based on AuNPs modified nitrocellulose membrane (NC membrane) was applied to detect bacterial proliferation through electrochemical impedance to accurately quantify antibiotics. The NC-AuNPs-Anti composite membrane was adopted for time-lapse effect of low concentration of amikacin sulfate on E. coli, and the change in AC impedance was analyzed by the equivalent model. t-SNE method was applied to visualize high-dimensional parameters and perform feature screening, and a machine learning model was adopted to accurately predict antibiotics. The experimental results show that this method can reach the antibiotic prediction accuracy of ±2.9E-<inline-formula> <tex-math notation="LaTeX">03 ~\mu \text{L} </tex-math></inline-formula>/mL at 2, 3, and 4 hours after dosing, so as to provide a better quantitative analysis method for accurate antibiotic evaluation through the electrochemical impedance detection by bacteria proliferation.
Halohydrin dehalogenases (HHDHs) are biocatalytically interesting enzymes due to their ability to form C-C, C-N, C-O, and C-S bonds. One of most important application of HHDH was the protein ...engineering of HheC (halohydrin dehalogenase from Agrobacterium radiobacter AD1) for the industrial manufacturing of ethyl (R)-4-cyano-3-hydroxybutanoate (HN), a key chiral synthon of a cholesterol-lowering drug of atorvastatin. During our development of an alternative, more efficient and economic route for chemo-enzymatic preparation of the intermediate of atorvastatin, we found that the HheC2360 previously reported for HN manufacture, had insufficient activity for the cyanolysis production of tert-butyl (3 R,5 S)-6-cyano-3,5-dihydroxyhexanoate (A7). Herein, we present the focused directed evolution of HheC2360 with higher activity and enhanced biocatalytic performance using active site mutagenesis. Through docking of the product, A7, into the crystal structure of HheC2360, 6 residues was selected for combined active sites testing (CASTing). After library screening, the variant V84G/W86F was identified to have a 15- fold increase in activity. Time course analysis of the cyanolysis reaction catalyzed by this variant, showed 2- fold increase in space time productivity compared with HheC2360. These results demonstrate the applicability of the variant V84G/W86F as a biocatalyst for the efficient and practical production of atorvastatin intermediate.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
The RING finger protein TRAIP protects genome integrity and its mutation causes Seckel syndrome. TRAIP encodes a nucleolar protein that migrates to UV-induced DNA lesions via a direct ...interaction with the DNA replication clamp PCNA. Thus far, mechanistically how UV mobilizes TRAIP from the nucleoli remains unknown. We found that PCNA binding is dispensable for the nucleolus-nucleoplasm shuttling of TRAIP following cell exposure to UV irradiation, and that its redistribution did not rely on the master DNA damage kinases ATM and ATR. Interestingly, I-PpoI-induced ribosomal DNA damage led to TRAIP exclusion from the nucleoli, raising the possibility that active ribosomal DNA transcription may underlie TRAIP retention in the nuclear sub-compartments. Accordingly, chemical inhibition of RNA polymerase I activity led to TRAIP diffusion into the nucleoplasm, and was coupled with marked reduction of DNA/RNA hybrids in the nucleoli, suggesting that TRAIP may be sequestered via binding to nucleic acid structures in the nucleoli. Consistently, cell pre-treatment with DNase/RNase effectively released TRAIP from the nucleoli. Taken together, our study defines a bipartite mechanism that drives TRAIP trafficking in response to UV damage, and highlights the nucleolus as a stress sensor that contributes to orchestrating DNA damage responses.
Attendance sign-in is a crucial component of the daily management of enterprises and institutions, but the current approaches of attendance have problems such as sign-in deceit and low efficiency of ...attendance data statistics. This paper designs and develops an attendance system based on RFID (Radio Frequency Identification Devices, RFID) and face recognition. By utilizing a composite authentication method with high recognition, the reliability of attendance management and the accuracy of attendance certification are enhanced. In this system, the attendance information of employees in enterprises and institutions can be intelligently managed. Moreover, the statistical efficiency of attendance data can also be effectively promoted, thus satisfying the daily attendance needs of enterprises and institutions.
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