74 research outputs found

    Land-Atmosphere Interaction in the Southwestern Karst Region of China

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    Land-atmosphere interaction in the southwestern Karst region of China was investigated from two aspects: response of land cover to climate change and climatic effects of Karst rocky desertification. The first part focused on the temporal-spatial variation of growing-season normalized difference vegetation index (NDVI) and its relationship with climate variables. The relationships between growing-season NDVI with temperature and precipitation were both positive, indicating its limiting role on the distribution and dynamic of vegetation cover in the study area. The second part was designed to investigate whether the changed vegetation cover and land surface processes in the Karst regions was capable of modifying the summer climate simulation over East Asia. It was shown that land desertification resulted in the reduced net radiation and evaporation in the degraded areas. The East Asian summer monsoon was weakened after land degradation. Such circulation differences favored the increase in moisture flux and clouds, and thereby causing more precipitation in southeast coastal areas. Based on the above findings, it can be concluded that vegetation cover in Karst region was sensitive to climate change at larger scale, and on the other hand, there was significant feedback of vegetation cover change to regional climate by altering water and energy balance

    Flexoelectricity-stabilized ferroelectric phase with enhanced reliability in ultrathin La:HfO2 films

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    Doped HfO2 thin films exhibit robust ferroelectric properties even for nanometric thicknesses, are compatible with current Si technology and thus have great potential for the revival of integrated ferroelectrics. Phase control and reliability are core issues for their applications. Here we show that, in (111)-oriented 5%La:HfO2 (HLO) epitaxial thin films deposited on (La0.3Sr0.7)(Al0.65Ta0.35)O3 substrates, the flexoelectric effect, arising from the strain gradient along the films normal, induces a rhombohedral distortion in the otherwise Pca21 orthorhombic structure. Density functional calculations reveal that the distorted structure is indeed more stable than the pure Pca21 structure, when applying an electric field mimicking the flexoelectric field. This rhombohedral distortion greatly improves the fatigue endurance of HLO thin films by further stabilizing the metastable ferroelectric phase against the transition to the thermodynamically stable non-polar monoclinic phase during repetitive cycling. Our results demonstrate that the flexoelectric effect, though negligibly weak in bulk, is crucial to optimize the structure and properties of doped HfO2 thin films with nanometric thicknesses for integrated ferroelectric applications

    Engineering allosteric inhibition of homoserine dehydrogenase by semi-rational saturation mutagenesis screening

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    Allosteric regulation by pathway products plays a vital role in amino acid metabolism. Homoserine dehydrogenase (HSD), the key enzyme for the biosynthesis of various aspartate family amino acids, is subject to feedback inhibition by l-threonine and l-isoleucine. The desensitized mutants with the potential for amino acid production remain limited. Herein, a semi-rational approach was proposed to relieve the feedback inhibition. HSD from Corynebacterium glutamicum (CgHSD) was first characterized as a homotetramer, and nine conservative sites at the tetramer interface were selected for saturation mutagenesis by structural simulations and sequence analysis. Then, we established a high-throughput screening (HTS) method based on resistance to l-threonine analog and successfully acquired two dominant mutants (I397V and A384D). Compared with the best-ever reported desensitized mutant G378E, both new mutants qualified the engineered strains with higher production of CgHSD-dependent amino acids. The mutant and wild-type enzymes were purified and assessed in the presence or absence of inhibitors. Both purified mutants maintained >90% activity with 10 mM l-threonine or 25 mM l-isoleucine. Moreover, they showed >50% higher specific activities than G378E without inhibitors. This work provides two competitive alternatives for constructing cell factories of CgHSD-related amino acids and derivatives. Moreover, the proposed approach can be applied to engineering other allosteric enzymes in the amino acid synthesis pathway

    APOBEC1 cytidine désaminase induit la mutagenèse de l'ADN chez différentes espèces animales

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    Les cytidine desaminases APOBEC1 (A1) ont une préférence claire pour le substrat pour l'ARN. De plus, il a été démontré que quelques enzymes A1 sont actives sur l'ADN simple brin, ce qui reflète les activités décrites pour les enzymes APOBEC3. Comme APOBEC3A (A3A) humain, APOBEC3B (A3B) humain et des enzymes apparentés appartenant au spectre des mammifères placentaires peuvent introduire des mutations dans l'ADN nucléaire conduisant à des génomes cancéreux, nous avons exploré la menace mutagène de la cytidine désaminase A1 sur l'ADN chromosomique.Utilisation de la 3D-PCR pour détecter des mutations spécifiques GC-AT d’APOBEC, nous avons démontré que les enzymes A1 de la vache, du porc, du chien, du lapin et de la souris avaient une spécificité de substrat intracellulaire d’ADN simple brin. Cependant, seule l'enzyme de souris était capable d'introduire des mutations dans l'ADN nucléaire. Fait intéressant, la souris A1 quitte le même contexte d’édition de dinucléotides (5’TpC) que les enzymes similaires à APOBEC3. Ces caractères ont été mis en parallèle par la désamination de l'ADN substitué de 5-méthylcytidine par A1 de souris, caractéristique des enzymes A3A et A3B de mammifères. L'enzyme A1 de la souris était beaucoup moins efficace que l'A3A humain et était plus proche de l'A3B humain.Au niveau expérimental, APOBEC1 chez la souris est remarquable parmi 12 enzymes de mammifères en ce sens qu’il représente une source de mutations somatiques dans le génome de la souris, alimentant potentiellement l’oncogenèse. Bien que l'ordre de Rodentia soit dépourvu d'un enzyme de type A3A, il semble qu'APOBEC1 pourrait bien le remplacer, tout en restant beaucoup moins actif. Cela modifie le paradigme selon lequel les enzymes APOBEC3 et AID sont les seules enzymes de mutation endogènes donnant lieu à une modification non ciblée des génomes de mammifères.APOBEC1 (A1) cytidine deaminases have a clear substrate preference for RNA. In addition, a few A1 enzymes have been shown to be active on single stranded DNA, mirroring the activities described for APOBEC3 enzymes. As human APOBEC3A (A3A), APOBEC3B (A3B) and related enzymes across the spectrum of placental mammals can introduce mutations in nuclear DNA leading to cancer genomes, we explored the mutagenic threat of A1 cytidine deaminases to chromosomal DNA.Using 3D-PCR to detect APOBEC specific GC to AT mutations, we demonstrated that A1 enzymes from the cow, pig, dog, rabbit and mouse have an intracellular ssDNA substrate specificity. However, only the mouse enzyme was able to introduce mutations into nuclear DNA. Interestingly, mouse A1 leaves the same dinucleotide editing context (5’TpC) as APOBEC3 like enzymes. These traits were paralleled by deamination of 5-methylcytidine substituted DNA by mouse A1 which is a feature of the mammalian A3A and A3B enzymes. Mouse A1 enzyme was far less efficient than human A3A and was closer to human A3B.At an experimental level mouse APOBEC1 is remarkable among 12 mammalian enzymes in that it represents a source of somatic mutations in mouse genome, potentially fueling oncogenesis. While the order of Rodentia is bereft of an A3A like enzyme it seems that APOBEC1 may well substitute for it, albeit remaining much less active. This modifies the paradigm that APOBEC3 and AID enzymes are the sole endogenous mutator enzymes giving rise to off-target editing of mammalian genomes

    Cloning and expression of a novel α-galactosidase from Lactobacillus amylolyticus L6 with hydrolytic and transgalactosyl properties.

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    Lactobacillus amylolyticus L6, a gram-positive amylolytic bacterium isolated from naturally fermented tofu whey (NFTW), was able to hydrolyze raffinose and stachyose for the production of α-galactosidase. The cell-free extract of L. amylolyticus L6 was found to exhibit glycosyltransferase activity to synthesize α-galacto-oligosaccharides (GOS) with melibiose as substrate. The coding genes of α-galactosidase were identified in the genome of L. amylolyticus L6. The α-galactosidase (AglB) was placed into GH36 family by amino acid sequence alignments with other α-galactosidases from lactobacilli. The optimal reaction conditions of pH and temperature for AglB were pH 6.0 and 37°C, respectively. Besides, potassium ion was found to improve the activity of AglB while divalent mercury ion, copper ion and zinc ion displayed different degrees of inhibition effect. Under the optimum reaction condition, AglB could catalyze the synthesis of GOS with degree of polymerization (DP) ≥5 by using 300 mM melibiose concentration as substrate. The maximum yield of GOS with (DP) ≥3 could reach 31.56% (w/w). Transgalactosyl properties made AglB a potential candidate for application in the production of GOS

    Lidocaine effects on neutrophil extracellular trapping and angiogenesis biomarkers in postoperative breast cancer patients with different anesthesia methods: a prospective, randomized trial

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    Abstract Background Anesthesia techniques and drug selection may influence tumor recurrence and metastasis. Neutrophil extracellular trapping (NETosis), an immunological process, has been linked to an increased susceptibility to metastasis in individuals with tumors. Furthermore, recurrence may be associated with vascular endothelial growth factor A (VEGF-A), a mediator of angiogenesis. This study investigates the impact of lidocaine (combined with sevoflurane or propofol anesthesia ) during breast cancer surgery inhibits the expression of biomarkers associated with metastasis and recurrence (specifically H3Cit, NE, MPO, MMP-9 and VEGF-A). Methods We randomly assigned 120 women undergoing primary or invasive breast tumor resection to receive one of four anesthetics: sevoflurane (S), sevoflurane plus i.v. lidocaine (SL), propofol (P), and propofol plus i.v. lidocaine (PL). Blood samples were collected before induction and 3 h after the operation. Biomarkers associated with NETosis (citrullinated histone H3 [H3Cit], myeloperoxidase [MPO], and neutrophil elastase [NE]) and angiogenesis were quantified using enzyme-linked immunosorbent assays. Results Patient and breast tumor characteristics, along with perioperative management, did not differ between study groups. In intra-group comparisons, S and P groups demonstrated a statistically significant increase in post-operative MPO (S group: 10.39[6.89–17.22] vs. 14.31[8.55–20.87] ng ml-1, P = 0.032; P group: 9.45[6.73–17.37] vs. 14.34[9.87–19.75] ng ml-1, P = 0.035)and NE(S group: 182.70[85.66-285.85] vs. 226.20[91.85-391.65] ng ml-1, P = 0.045; P group: 154.22[97.31–325.30] vs. 308.66[132.36-483.57] ng ml-1, P = 0.037) concentrations compared to pre-operative measurements, whereas SL and PL groups did not display a similar increase. H3Cit, MMP-9, and VEGF-A concentrations were not significantly influenced by the anesthesia techniques and drugs. Conclusions Regardless of the specific technique employed for general anesthesia, there was no increase in the postoperative serum concentrations of MPO and NE after perioperative lidocaine infusion compared to preoperative serum concentrations. This supports the hypothesis that intravenous lidocaine during cancer surgery aimed at achieving a cure may potentially decrease the likelihood of recurrence. Further interpretation and discussion of clinical implications are warranted, emphasizing the significance of these findings in the context of cancer surgery and recurrence prevention. Clinical trial registration ChiCTR2300068563
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