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1.
Molecules ; 26(21)2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34770884

RESUMO

Semiconducting metal oxides can detect low concentrations of NO2 and other toxic gases, which have been widely investigated in the field of gas sensors. However, most studies on the gas sensing properties of these materials are carried out at high temperatures. In this work, Hollow SnO2 nanofibers were successfully synthesized by electrospinning and calcination, followed by surface modification using ZnO to improve the sensitivity of the SnO2 nanofibers sensor to NO2 gas. The gas sensing behavior of SnO2/ZnO sensors was then investigated at room temperature (~20 °C). The results showed that SnO2/ZnO nanocomposites exhibited high sensitivity and selectivity to 0.5 ppm of NO2 gas with a response value of 336%, which was much higher than that of pure SnO2 (13%). In addition to the increase in the specific surface area of SnO2/ZnO-3 compared with pure SnO2, it also had a positive impact on the detection sensitivity. This increase was attributed to the heterojunction effect and the selective NO2 physisorption sensing mechanism of SnO2/ZnO nanocomposites. In addition, patterned electrodes of silver paste were printed on different flexible substrates, such as paper, polyethylene terephthalate and polydimethylsiloxane using a facile screen-printing process. Silver electrodes were integrated with SnO2/ZnO into a flexible wearable sensor array, which could detect 0.1 ppm NO2 gas after 10,000 bending cycles. The findings of this study therefore open a general approach for the fabrication of flexible devices for gas detection applications.

2.
Cell Death Dis ; 12(11): 1052, 2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34741044

RESUMO

STEAP3 (Six-transmembrane epithelial antigen of the prostate 3, TSAP6, dudulin-2) has been reported to be involved in tumor progression in human malignancies. Nevertheless, how it participates in the progression of human cancers, especially HCC, is still unknown. In the present study, we found that STEAP3 was aberrantly overexpressed in the nuclei of HCC cells. In a large cohort of clinical HCC tissues, high expression level of nuclear STEAP3 was positively associated with tumor differentiation and poor prognosis (p < 0.001), and it was an independent prognostic factor for HCC patients. In HCC cell lines, nuclear expression of STEAP3 significantly promoted HCC cells proliferation by promoting stemness phenotype and cell cycle progression via RAC1-ERK-STAT3 and RAC1-JNK-STAT6 signaling axes. Through upregulating the expression and nuclear trafficking of EGFR, STEAP3 participated in regulating EGFR-mediated STAT3 transactivity in a manner of positive feedback. In summary, our findings support that nuclear expression of STEAP3 plays a critical oncogenic role in the progression of HCC via modulation on EGFR and intracellular signaling, and it could be a candidate for prognostic marker and therapeutic target in HCC.

3.
Int J Gen Med ; 14: 7545-7555, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34754227

RESUMO

Background: The platelet-to-lymphocyte ratio (PLR) is an inflammation marker of acute ischemic stroke, but its significance in patients with hemorrhage transformation (HT) after acute ischemic stroke with large-artery atherosclerosis (AIS-LAA) is unclear, and we also identified the relationship between PLR and in-hospital mortality of HT after AIS-LAA. Methods: This was a retrospective analysis of patients with AIS-LAA. The PLR was calculated according to platelet and lymphocyte counts on admission. HT was defined on follow-up magnetic resonance imaging or computed tomography when neurologic deterioration worsened during hospitalization. The univariate analysis and multivariate logistic regression were performed to assess the association of PLR, HT and in-hospital mortality of HT after AIS-LAA. Results: We included 328 Chinese AIS-LAA patients (mean age 67.2±11.1 years; 70.4% male). HT occurred in 38 patients (11.6%). After multivariate regression analyses, NRL (odds ratio [OR] 1.354, 95% confidence interval [CI] 1.176-1.559, P<0.001) and PLR (odds ratio [OR] 3.869, 95% confidence interval [CI] 2.233-5.702, P<0.001) were independently associated with HT after AIS-LAA. The area under the ROC curve (AUC) value of PLR (0.72, 95% CI (0.64-0.80), P<0.001) tested a greater discriminatory ability compared with neutrophil-lymphocyte ratio (NLR) (0.67, 95% CI (0.58-0.76), P<0.001). Meanwhile, PLR was found to be significantly related to HT after AIS-LAA, including in subtypes of artery-to-artery embolization (aOR 1.699, 95% CI 1.298-3.215, P<0.001), in-situ thrombosis (aOR4.499, 95% CI 1.344-9.054, P<0.001) and branch atheromatous disease (aOR3.239, 95% CI 1.098-8.354, P<0.001). Increased PLR predicts high in-hospital mortality of HT after AIS-LAA (OR 1.041, 95% CI (1.006-1.077), P=0.020; aOR 1.053, 95% CI (1.004-1.104), P=0.034). Conclusion: High PLR is associated with greater risk of HT in AIS-LAA patients, including in artery-to-artery embolization, in-situ thrombosis and branch atheromatous disease. Meanwhile, increased PLR predicts high in-hospital mortality of HT after AIS-LAA.

4.
Langmuir ; 37(47): 13903-13908, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34792360

RESUMO

The strong affinity of water to zeolite adsorbents has made adsorption of CO2 from humid gas mixtures such as flue gas nearly impossible under equilibrated conditions. Here, in this manuscript, we describe a unique cooperative adsorption mechanism between H2O and Cs+ cations on Cs-RHO zeolite, which actually facilitates the equilibrium adsorption of CO2 under humid conditions. Our data demonstrate that, at a relative humidity of 5%, Cs-RHO adsorbs 3-fold higher amounts of CO2 relative to dry conditions, at a temperature of 30 °C and CO2 pressure of 1 bar. A comparative investigation of univalent cation-exchanged RHO zeolites with H+, Li+, Na+, K+, Rb+, and Cs+ shows an increase of equilibrium CO2 adsorption under humid versus dry conditions to be unique to Cs-RHO. In situ powder X-ray diffraction indicates the appearance of a new phase with Im3̅m symmetry after H2O saturation of Cs-RHO. A mixed-cation exchanged NaCs-RHO exhibits similar phase transitions after humid CO2 adsorption; however, we found no evidence of cooperativity between Cs+ and Na+ cations in adsorption, in single-component H2O and CO2 adsorption. We hypothesize based on previous Rietveld refinements of CO2 adsorption in Cs-RHO zeolite that the observed phase change is related to solvation of extra-framework Cs+ cations by H2O. In the case of Cs-RHO, molecular modeling results suggest that hydration of these cations favors their migration from an original D8R position to S8R sites. We posit that this movement enables a trapdoor mechanism by which CO2 can interact with Cs+ at S8R sites to access the α-cage.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34815081

RESUMO

Lithium (Li) metal is deemed as an ideal and promising star anode for high energy storage but its application still is impeded due to uncontrollable Li dendrite growth and tremendous dimension change. Although the flexible and conductive three-dimensional (3D) skeleton can improve the structural and interfacial stability of Li anode, its inherently lithiophobic feature usually brings a high nucleation barrier, uneven Li+ flux, and large concentration polarization, leading to inhomogeneous Li plating/stripping. Here, we develop target material (denoted as Mo2C NPs@CC) consisting of well-distributed molybdenum carbide nanoparticles (Mo2C NPs) with intrinsic lithiophilicity serving as lithiophilic seeds implanted onto the carbon cloth, breaking the dilemma of ordinary 3D conductive skeletons. The Mo2C NPs with large Li absorption energy provide plentiful lithiophilic sites for guiding the uniform and thin Li-nuclei layer formation, thereby realizing flat Li growth and stable electrode/electrolyte interface. Moreover, the high electronic conductivity of Mo2C-modified 3D scaffolds can balance the lithiophilicity, ensuring the fast electron transport in the whole electrode, effectively lowering the local current density, and providing enough space for buffering volume change, and synergistically suppresses the growth of Li dendrites. As a result, a prolonged lifespan of 5000 cycles with low voltage hysteresis of 10 mV at current density of 2 mA cm-2 with area capacity (Ca) of 1 mA h cm-2 has been achieved, giving rational guidance for designing high-performance composite Li anodes.

6.
Foods ; 10(11)2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34829168

RESUMO

Antarctic krill oil is an emerging marine lipid and expected to be a potential functional food due to its diverse nutrients, such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), phospholipids, astaxanthin and tocopherols. Although krill oil has been previously proved to have anti-inflammatory activity, there is little information about the relationship between its chemical compositions and anti-inflammatory activity. In this study, the RAW264.7 macrophages model was used to elucidate and compare the anti-inflammatory potential of different krill lipid fractions: KLF-A, KLF-H and KLF-E, which have increasing phospholipids, EPA and DHA contents but decreasing astaxanthin and tocopherols levels. Results showed that all the krill lipid fractions alleviated the inflammatory reaction by inhibition of production of nitric oxide (NO), release of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-6 and gene expression of proinflammatory mediators including TNF-α, IL-1ß, IL-6, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). In addition, KLF-E with the highest phospholipids, EPA and DHA contents showed the strongest inhibition effect on the LPS-induced proinflammatory mediator release and their gene expressions. The results would be helpful to provide powerful insights into the underlying anti-inflammatory mechanism of krill lipid and guiding the production of krill oil products with tailor-made anti-inflammatory activity.

7.
Oncogene ; 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34845378

RESUMO

Hyperactivation of RAS/MAPK signaling is commonly observed in hepatocellular carcinoma (HCC). Gain-of-function mutations of canonical RAS genes, however, are rarely detected and it remains unclear how the activity of this pathway is turned on during hepatocarcinogenesis. We performed a comprehensive analysis of RAS superfamily genetic alterations across ten subfamilies, 152 members in 377 HCC patients from the Cancer Genome Atlas database. RIT1 (Ras-like without CAAX 1) was the most frequently altered RAS member amplified in 13% of the HCC cohort. Both genomic amplification and CREB-mediated transcriptional activation contributed to the elevated RIT1 expression, and its overexpression correlated with RAS/MAPK activation and poor prognosis. Then, we found that RIT1-induced angiogenesis via the MEK/ERK/EIF4E/HIF1-α/VEGFA axis. MAP3K11 and MAP3K12, in addition to CRAF, could mediate this process by binding to RIT1. Moreover, RIT1 increased the phosphorylation of p38 MAPK and AKT to promote cell survival under reactive oxygen species stress. Based on this mechanistic understanding, we treated RIT1-overexpressing HCC with combined regimen sorafenib plus AKT inhibitor, and achieved enhanced antitumor effects in vivo. Our study reveals RAS "orphan" member RIT1 as the most common genetic alteration of RAS family in HCC and combination of sorafenib with AKT inhibitor might be a promising treatment strategy for RIT1-overexpressing HCC.

8.
Oncogene ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645979

RESUMO

Colorectal carcinoma (CRC) is the second most deadly cancer worldwide. Therapies that take advantage of DNA repair defects have been explored in various tumors but not yet systematically in CRC. Here, we found that Diphosphoinositol Pentakisphosphate Kinase 2 (PPIP5K2), an inositol pyrophosphate kinase, was highly expressed in CRC and associated with a poor prognosis of CRC patients. In vitro and in vivo functional studies demonstrated that PPIP5K2 could promote the proliferation and migration ability of CRC cells independent of its inositol pyrophosphate kinase activity. Mechanically, S1006 dephosphorylation of PPIP5K2 could accelerate its dissociation with 14-3-3 in the cytoplasm, resulting in more nuclear distribution. Moreover, DNA damage treatments such as doxorubicin (DOX) or irradiation (IR) could induce nuclear translocation of PPIP5K2, which subsequently promoted homologous recombination (HR) repair by binding and recruiting RPA70 to the DNA damage site as a novel scaffold protein. Importantly, we verified that S1006 dephosphorylation of PPIP5K2 could significantly enhance the DNA repair ability of CRC cells through a series of DNA repair phenotype assays. In conclusion, PPIP5K2 is critical for enhancing the survival of CRC cells via facilitating DNA HR repair. Our findings revealed an unrecognized biological function and mechanism model of PPIP5K2 dependent on S1006 phosphorylation and provided a potential therapeutic target for CRC patients.

9.
Exp Ther Med ; 22(6): 1357, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34659503

RESUMO

Picrasma quassioides (D. Don) Benn is an Asian shrub with a considerable history of traditional medicinal use. P. quassioides and its extracts exhibit good therapeutic properties against several diseases, including anti-inflammatory, antibacterial and anticancer effects. However, the composition of compounds contained in P. quassioides is complex; although various studies have examined mixtures or individual compounds extracted from it, studies on the application of P. quassioides extracts remain limited. In the present review, the structures and functions of the compounds identified from P. quassioides and their utility in anti-inflammatory, anticancer and neuroprotectant therapies was discussed. The present review provided up-to-date information on pharmacological activities and clinical applications for P. quassioides extracts.

10.
Int J Womens Health ; 13: 991-1004, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712062

RESUMO

Background: Myocardial infarction associated transcript (MIAT) is identified as a long chain non-coding RNA (lncRNA), which was associated with myocardial infarction susceptibility. While intense efforts have been made to elucidate the relationship between MIAT and carcinogenesis, the tumor immunoreaction of MIAT remains elusive. Thus, this study aimed to investigate the role of MIAT in the immunoregulation of breast cancer (BC) and further explore the better clinical significance. Methods: The differential expression of MIAT between BC and normal/adjacent tissues was compared using Wilcoxon rank sum test. The diagnostic and prognostic values of elevated MIAT expression in BC tissues were unveiled via receiver operating characteristic (ROC) analysis and KM-plotter analysis. Limma and edgeR package were used to identify differentially expressed genes (DEGs) and microRNAs (DEMs) from TCGA database respectively. A co-expression dataset was constructed to comprehensively understand the relationship between MIAT and DEGs based on the Pearson correlation coefficient. Furthermore, GO and KEGG analyses were conducted to predict the potential functions of MIAT. We next intersected immune-related genes (IRGs) from ImmPort database with MIAT-co-expressed genes to obtain MIAT-co-expressed IRGs, in order to construct MIAT-microRNA (miRNA)-mRNA network. And the correlation between MIAT and tumor-infiltrating immune cells (TICs) and immunophenoscore (IPS) analysis was analyzed by TIMER and CIBERSORT. Finally, the reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression profiles of MIAT in serum samples. Results: The expression levels of MIAT were notably higher in BC than in normal or adjacent tissues. And MIAT expression could be used as a prognostic indicator of mortality risk in patients with BC in different aspects. Moreover, the enrichment analyses suggested that MIAT was strongly involved in BC immune response. In addition, TIMER database and CIBERSORT analyses indicated that MIAT was significantly correlated with 13 types of TICs (B cells, dendritic cells, neutrophils, CD8 T cells, CD4 memory resting T cells, CD4 memory activated T cells, gamma delta T cells, M1 macrophages, plasma cells, activated NK cells, monocytes, M2 macrophages, activated mast cells). Simultaneously, the IPS analysis implied that the higher the MIAT expression, the better the immunotherapy effect. The ROC curve analysis showed that the area under the curve (AUC) value of MIAT was 0.86 (sensitivity = 87.80%, specificity = 75.61%). And the high MIAT expression in serum was positive related to TNM stage (P = 0.032) and lymph node metastasis (P = 0.028). Conclusion: MIAT may be a valuable noninvasive diagnostic biomarker for BC and is associated with tumor-infiltrating immune cells in tumor microenvironment, suggesting MIAT as a potential target for future treatment of BC.

12.
Front Oncol ; 11: 723137, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34476219

RESUMO

The E2F family of transcription factors (E2Fs) consist of eight genes in mammals. These genes encode ten proteins that are usually classified as transcriptional activators or transcriptional repressors. E2Fs are important for many cellular processes, from their canonical role in cell cycle regulation to other roles in angiogenesis, the DNA damage response and apoptosis. A growing body of evidence demonstrates that cancer stem cells (CSCs) are key players in tumor development, metastasis, drug resistance and recurrence. This review focuses on the role of E2Fs in CSCs and notes that many signals can regulate the activities of E2Fs, which in turn can transcriptionally regulate many different targets to contribute to various biological characteristics of CSCs, such as proliferation, self-renewal, metastasis, and drug resistance. Therefore, E2Fs may be promising biomarkers and therapeutic targets associated with CSCs pathologies. Finally, exploring therapeutic strategies for E2Fs may result in disruption of CSCs, which may prevent tumor growth, metastasis, and drug resistance.

13.
Micromachines (Basel) ; 12(9)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34577655

RESUMO

Edge computing is a new paradigm, which provides storage, computing, and network resources between the traditional cloud data center and terminal devices. In this paper, we concentrate on the application-driven task offloading problem in edge computing by considering the strong dependencies of sub-tasks for multiple users. Our objective is to joint optimize the total delay and energy generated by applications, while guaranteeing the quality of services of users. First, we formulate the problem for the application-driven tasks in edge computing by jointly considering the delays and the energy consumption. Based on that, we propose a novel Application-driven Task Offloading Strategy (ATOS) based on deep reinforcement learning by adding a preliminary sorting mechanism to realize the joint optimization. Specifically, we analyze the characteristics of application-driven tasks and propose a heuristic algorithm by introducing a new factor to determine the processing order of parallelism sub-tasks. Finally, extensive experiments validate the effectiveness and reliability of the proposed algorithm. To be specific, compared with the baseline strategies, the total cost reduction by ATOS can be up to 64.5% on average.

14.
Cell Rep ; 36(10): 109660, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34496260

RESUMO

Non-small cell lung carcinoma (NSCLC), the most common form of lung cancer, is the leading cause of cancer-related death worldwide. We perform whole-genome sequencing (WGS) on samples from 43 primary patients with NSCLC and matched normal samples and analyze their matched open chromatin data and transcriptome data. Our results indicate that next-generation sequencing (NGS) and the Bionano Genomics (BNG) platform should be viewed as complementary technologies in terms of structural variations detection. By creating a framework integrating these two platforms, we detect high-technical-confidence somatic structural variations (SVs) in NSCLC cases, which could aid in the efficient investigation of new candidate oncogenes, such as TRIO and SESTD1. Our findings highlight the impact of somatic SVs on NSCLC oncogenesis and lay a foundation for exploring associations among somatic SVs, gene expression, and regulatory networks in patients with NSCLC.

15.
Genome Med ; 13(1): 148, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507604

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a major cancer type whose mechanism of metastasis remains elusive. METHODS: In this study, we characterised the evolutionary pattern of metastatic CRC (mCRC) by analysing bulk and single-cell exome sequencing data of primary and metastatic tumours from 7 CRC patients with liver metastases. Here, 7 CRC patients were analysed by bulk whole-exome sequencing (WES); 4 of these were also analysed using single-cell sequencing. RESULTS: Despite low genomic divergence between paired primary and metastatic cancers in the bulk data, single-cell WES (scWES) data revealed rare mutations and defined two separate cell populations, indicative of the diverse evolutionary trajectories between primary and metastatic tumour cells. We further identified 24 metastatic cell-specific-mutated genes and validated their functions in cell migration capacity. CONCLUSIONS: In summary, scWES revealed rare mutations that failed to be detected by bulk WES. These rare mutations better define the distinct genomic profiles of primary and metastatic tumour cell clones.

16.
Mol Psychiatry ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34588622

RESUMO

Epigenetic modifications are plausible molecular sources of phenotypic heterogeneity across schizophrenia patients. The current study investigated biological heterogeneity in schizophrenia using peripheral epigenetic profiles to delineate illness subtypes independent of their phenomenological manifestations. We applied epigenome-wide profiling with a DNA methylation array from blood samples of 63 schizophrenia patients and 59 healthy controls. Non-negative matrix factorization (NMF) and k-means clustering were performed to identify DNA methylation-related patient subtypes. The validity of the partition was tested by assessing the profile of the T cell receptor (TCR) repertoires. The uniqueness of the identified subtypes in relation to brain structural and clinical measures were evaluated. Two distinct patterns of DNA methylation profiles were identified in patients. One subtype (60.3% of patients) showed relatively limited changes in methylation levels and cell composition compared to controls, while a second subtype (39.7% of patients) exhibited widespread methylation level alterations among genes enriched in immune cell activity, as well as a higher proportion of neutrophils and lower proportion of lymphocytes. Differentiation of the two patient subtypes was validated by TCR repertoires, which paralleled the partition based on DNA methylation profiles. The subtype with widespread methylation modifications had higher symptom severity, performed worse on cognitive measures, and displayed greater reductions in fractional anisotropy of white matter tracts and evidence of gray matter thickening compared to the other subtype. Identification of a distinct subtype of schizophrenia with unique molecular, cerebral, and clinical features provide a novel parcellation of the schizophrenia syndrome with potential to guide development of individualized therapeutics.

17.
Mol Med Rep ; 24(5)2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34476500

RESUMO

Cisplatin (DDP) resistance in patients suffering from ovarian cancer is a considerable hurdle to successful treatment. The present study aimed to identify a possible long non­coding RNA (lncRNA)­microRNA (miRNA)­mRNA axis participating in ovarian cancer DDP­resistance based on the critical roles of non­coding RNAs, including lncRNAs and miRNAs, in carcinogenesis. According to online data and experimental results, lncRNA HAND2­AS1 expression was significantly downregulated within ovarian carcinoma, especially within recurrent and DDP­resistant ovarian carcinoma. The expression of HAND2­AS1 was also shown to be markedly inhibited in SKOV3/DDP (DDP) cells with resistance to DDP. In SKOV3/DDP cells, HAND2­AS1 overexpression inhibited cell viability and promoted cell apoptosis upon DDP treatment through the Bcl­2/caspase­3 apoptotic signaling. It was hypothesized that PTEN mRNA expression was also markedly inhibited in SKOV3/DDP ovarian cancer cells, while HAND2­AS1 overexpression rescued PTEN proteins and blocked PI3K/AKT signaling activation. Moreover, miR­106a was found to bind directly to PTEN 3' UTR and HAND2­AS1. Upon DDP treatment, miR­106a overexpression in SKOV3/DDP cells promoted cell viability. It inhibited cell apoptosis through the Bcl­2/caspase­3 apoptotic signaling pathway and downregulated the protein levels of PTEN and upregulated PI3K/AKT signaling activity. Furthermore, miR­106a overexpression partially reversed the effect of HAND2­AS1 overexpression upon PTEN proteins and SKOV3/DDP cell proliferation upon DDP treatment. In conclusion, a lncRNA HAND2­AS1/miR­106a/PTEN axis that re­sensitizes DDP­resistant SKOV3/DDP cells to DDP treatment has been established.

18.
Metab Eng ; 68: 119-130, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34592433

RESUMO

Bottlenecks in the efficient conversion of xylose into cost-effective biofuels have limited the widespread use of plant lignocellulose as a renewable feedstock. The yeast Saccharomyces cerevisiae ferments glucose into ethanol with such high metabolic flux that it ferments high concentrations of glucose aerobically, a trait called the Crabtree/Warburg Effect. In contrast to glucose, most engineered S. cerevisiae strains do not ferment xylose at economically viable rates and yields, and they require respiration to achieve sufficient xylose metabolic flux and energy return for growth aerobically. Here, we evolved respiration-deficient S. cerevisiae strains that can grow on and ferment xylose to ethanol aerobically, a trait analogous to the Crabtree/Warburg Effect for glucose. Through genome sequence comparisons and directed engineering, we determined that duplications of genes encoding engineered xylose metabolism enzymes, as well as TKL1, a gene encoding a transketolase in the pentose phosphate pathway, were the causative genetic changes for the evolved phenotype. Reengineered duplications of these enzymes, in combination with deletion mutations in HOG1, ISU1, GRE3, and IRA2, increased the rates of aerobic and anaerobic xylose fermentation. Importantly, we found that these genetic modifications function in another genetic background and increase the rate and yield of xylose-to-ethanol conversion in industrially relevant switchgrass hydrolysate, indicating that these specific genetic modifications may enable the sustainable production of industrial biofuels from yeast. We propose a model for how key regulatory mutations prime yeast for aerobic xylose fermentation by lowering the threshold for overflow metabolism, allowing mutations to increase xylose flux and to redirect it into fermentation products.


Assuntos
Proteínas de Saccharomyces cerevisiae , Xilose , Biocombustíveis , Fermentação , Glucose , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
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