Light-flavour Baijiu is a type of Chinese liquor with a pure and mild flavour produced by traditional spontaneous solid-state fermentation. The flavour of this liquor has been found to vary in the ...different periods of annual production. To explore the factors affecting flavour, the microbiota of the surrounding environment, starter and fermentation process in different periods were investigated. Results showed that the ester content and acidity of light-flavour Baijiu were significantly lower when annual production was resumed after a summer break. HCA plot of volatile flavour profile and bacterial PCoA results indicated that the differences occurred at later stages, mainly due to different structures of Lactobacillus. Correlation analysis by O2PLS indicated that Lactobacillus positively correlated with esters. Species-level analysis showed that the lack of L. acetotolerans on the surface of the jar might cause a lag in fermentation and lower ester content. Thereafter, L. acetotolerans was revived during fermentation and enriched on the surface of the jar, which promoted ester formation. As important sources of L. acetotolerans, the air and fermentation jars played a critical role during fermentation. Therefore, this systematic study on environmental microbial ecology is valuable for quality control and to explore environmental microbiota functions during spontaneous fermentation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Ethylene/polar monomer coordination copolymerization offers an attractive way of making functionalized polyolefins. However, ethylene copolymerization with industrially relevant short chain length ...alkenoic acid remain a big challenge. Here we report the efficient direct copolymerization of ethylene with vinyl acetic acid by tetranuclear nickel complexes. The protic monomer can be extended to acrylic acid, allylacetic acid, ω-alkenoic acid, allyl alcohol, and homoallyl alcohol. Based on X-ray analysis of precatalysts, control experiments, solvent-assisted electrospray ionization-mass spectrometry detection of key catalytic intermediates, and density functional theory studies, we propose a possible mechanistic scenario that involves a distinctive vinyl acetic acid enchainment enabled by Ni···Ni synergistic effects. Inspired by the mechanistic insights, binuclear nickel catalysts are designed and proved much more efficient for the copolymerization of ethylene with vinyl acetic acid or acrylic acid, achieving the highest turnover frequencies so far for both ethylene and polar monomers simultaneously.
The t(8;21) fusion product, AML1/ETO, and hypoxia-inducible factor 1α (HIF1α) form a feed-forward transcription loop that cooperatively transactivates the DNA methyltransferase 3a gene promoter that ...leads to DNA hypermethylation and drives leukemia cell growth. Suppression of the RNA N
-methyladenosine (m
A)-reader enzyme YTH N
-methyladenosine RNA binding protein 2 (YTHDF2) specifically compromises cancer stem cells in acute myeloid leukemia (AML) but promotes hematopoietic stem cell expansion without derailing normal hematopoiesis. However, the relevance of expression between AML1/ETO-HIF1α loop and YTHDF2, and its functional relationship with t(8;21) AML have not been documented. Here, we show that YTHDF2 is highly expressed in t(8;21) AML patients and associated with a higher risk of relapse and inferior relapse-free survival. Knockdown of YTHDF2 in leukemia cells causes an impaired cell proliferation rate in vitro and in mice. Mechanistically, HIF1α is able to bind to the hypoxia-response elements of the 5'-untranslated region of the YTHDF2 gene and promotes the transactivity of the YTHDF2 promoter. Knockdown and overexpression of either AML1/ETO or HIF1α resulted in decreased and increased YTHDF2 protein and mRNA expression in t(8;21) AML cells. In particular, knockdown of YTHDF2 resulted in increased global mRNA m
A levels in t(8;21) AML cells, accompanied by increased TNF receptor superfamily member 1b (TNFRSF1b) mRNA and protein expression levels. Last, we demonstrated that the m
A methylation and expression levels of the TNFRSF1b gene were both negatively correlated with HIF1α expression levels. In conclusion, YTHDF2 is a downstream target of the AML1/ETO-HIF1α loop and promotes cell proliferation probably by modulating the global m
A methylation in t(8;21) AML.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In this article, we propose an active kriging-based learning method for hybrid reliability analysis (HRA) with random and interval variables. An improved sampling strategy is proposed to target the ...sampling areas. Samples with maximum responses greater than 0 and minimum responses less than 0 are selected and regarded as the candidate samples; then, a U -based learning function is developed in which multiple samples of the interval are considered instead of one particular sample. To terminate the proposed method, a hybrid convergence criterion is proposed. Finally, an improved optimization strategy based on the DIRECT algorithm is developed for the Monte Carlo simulation conducted for the HRA. The performance of the proposed method is demonstrated by four numerical cases. The results illustrate that the proposed method is accurate and efficient for HRA.
AML1-ETO fusion protein (AE) is generated by t(8;21)(q22;q22) chromosomal translocation, which is one of the most frequently observed structural abnormalities in acute myeloid leukemia (AML) and ...displays a pivotal role in leukemogenesis. The histone acetyltransferase p300 promotes self-renewal of leukemia cells by acetylating AE and facilitating its downstream gene expression as a transcriptional coactivator, suggesting that p300 may be a potential therapeutic target for AE-positive AML. However, the effects of p300 inhibitors on leukemia cells and the underlying mechanisms have not been extensively investigated. In the current study, we analyzed the anti-leukemia effects of C646, a selective and competitive p300 inhibitor, on AML cells. Results showed that C646 inhibited cellular proliferation, reduced colony formation, evoked partial cell cycle arrest in G1 phase, and induced apoptosis in AE-positive AML cell lines and primary blasts isolated from leukemic mice and AML patients. Nevertheless, no significant inhibitory effects were observed in granulocyte colony-stimulating factor-mobilized normal peripheral blood stem cells. Notably, AE-positive AML cells were more sensitive to lower C646 doses than AE-negative ones. And C646-induced growth inhibition on AE-positive AML cells was associated with reduced global histone H3 acetylation and declined c-kit and bcl-2 levels. Therefore, C646 may be a potential candidate for treating AE-positive AML.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Steroid‐refractory (SR) acute graft‐versus‐host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). We investigated ...the efficacy, safety, prognostic factors, and optimal therapeutic protocol for SR‐aGVHD patients treated with basiliximab in a real‐world setting. Nine hundred and forty SR‐aGVHD patients were recruited from 36 hospitals in China, and 3683 doses of basiliximab were administered. Basiliximab was used as monotherapy (n = 642) or in combination with other second‐line treatments (n = 298). The cumulative incidence of overall response rate (ORR) at day 28 after basiliximab treatment was 79.4% (95% confidence interval CI 76.5%–82.3%). The probabilities of nonrelapse mortality and overall survival at 3 years after basiliximab treatment were 26.8% (95% CI 24.0%–29.6%) and 64.3% (95% CI 61.2%–67.4%), respectively. A 1:1 propensity score matching was performed to compare the efficacy and safety between the monotherapy and combined therapy groups. Combined therapy did not increase the ORR; conversely, it increased the infection rates compared with monotherapy. The multivariate analysis showed that combined therapy, grade III–IV aGVHD, and high‐risk refined Minnesota aGVHD risk score before basiliximab treatment were independently associated with the therapeutic response. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real‐world data suggest that basiliximab is safe and effective for treating SR‐aGVHD.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•How to constrain the agent’s behavior becomes the key to ensure the value and supply of the emergency supplies.•The efforts exerted by the enterprise are critical to the supply chain benefits during ...long-term agent reservation.•Incentive Contract can constraint the agent’s behaviors and urge the agent exerting more efforts.•Incentive Contract is a method to negotiate the relationships between the two-parties in supply chain,•Incentive Contract can resolve the possible benefits conflicts between two parties in supply chain.
Agent reserve strategy have experienced increased popularity in recent decades. In such a reservation method, the amount of effort exerted by an enterprise has significant influence on the value and supply capacity of emergency materials. When the interests of the government and the enterprise are not aligned, combined with poor information sharing, the members of the enterprise are more likely to suffer from emotional burnout, especially when considering long-term contract periods. Thus, the enterprise usually cannot consciously act in accordance with the government’s wishes. We extend the one-period incentive contract model to multi-periods to constrain the enterprise’s behavior and stimulate it to exert more effort. We conduct a numerical experiment to illustrate the changes in the two parties’ benefits over the contract period using the MATLAB experimental platform. The results show that both parties can benefit, and the incentive power of a multi-period incentive contract is better than that of a one-period contract. Furthermore, we analyze and determine the optimal cooperation period and the optimal joint profit. The practical purpose of using a multi-period incentive contract is steady improvement in emergency supplies’ capabilities and a strengthening of the enterprise’s effort, which lead to long-term benefits for both the government and the enterprise and valuable suggestions for the government’s decision-making.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
A study on a commuter's exposure to black carbon (BC) in five different traffic modes (taxi, bus, subway, cycling and walking) was conducted in Xuhui District, Shanghai. A commuter's real-time ...exposure concentrations were recorded by MicroAeth AE51 BC monitors, and the average BC exposure concentration and inhalation dose were analyzed. Data collected by cyclist was applied to characterize the micro-variability in relation to traffic density and street topology. The distance to the traffic and the street topology as well as the volume of heavy diesel trucks were the dominant factors influencing the BC concentrations. In this study, a high variability of BC concentrations between streets and even within streets was observed, and also between days and hour of the day. The average BC exposure concentrations were 5.59±1.02μg/m3, 6.58±1.78μg/m3, 7.28±1.87μg/m3, 8.62±4.13μg/m3 and 9.43±2.89μg/m3 for walking, cycling, bus, taxi and subway trips, respectively. Exposure levels of in-vehicle microenvironments were 8.66±3.66μg/m3, 9.39±6.98μg/m3 and 10.96±2.72μg/m3 for bus, taxi and subway, respectively. While inhalation doses were 0.68±0.33μg, 0.95±0.29μg, 1.36±0.37μg, 1.50±0.39μg and 1.58±0.29μg for taxi, subway, cycling, bus and walking, respectively. BC exposure level of walking was the lowest among all the traffic modes, but its inhalation dose was the highest.
•The exposure level in subway was the highest among the concerned modes.•The doses by bus and walking were higher compared to those by other modes.•Diesel vehicles are an important contributor to on-road BC concentrations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
An investigation of the fruiting bodies of edible mushroom Ganoderma lucidum produced 13 steroids, containing one new lanostane-type triterpene compound, named ganoderterpene A (1). Nuclear magnetic ...resonance and high-resolution electrospray ionization mass spectrometry data were used to deduce these structures. All the isolates were evaluated for their ability to suppress NO generation in BV-2 microglial cells treated with lipopolysaccharide (LPS) and exhibited moderate to strong inhibition effects, with IC50 values in the range 7.15–36.88 μM. Among the tested compounds, compound 1 exhibited the most marked activity with an IC50 value of 7.15 μM, and the structure–activity relationships were studied. This study showed that compound 1 significantly suppressed the activation of MAPK and TLR-4/NF-κB signaling pathways, as evidenced by an immunofluorescence assay and a molecular docking experiment. Furthermore, compound 1 effectively improved the LPS-induced mitochondrial membrane potential and apoptosis. These findings suggest that ganoderterpene A could exert protective effects in microglial cells from apoptosis by restraining the inflammatory response. Hence, G. lucidum could be used as a novel preventative agent for neurodegenerative disorders.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
To explore the efficacy and safety of G-SCF-mobilized donor lymphocyte infusion (DLI) for treatment of relapse of hematologic malignancies after allogeneic peripheral blood stem cell transplantation, ...we performed a retrospective analysis in a cohort of patients with morphologic (
n
= 36) or molecular (
n
= 22) relapse post transplantation. The 3-year post-DLI survival rates for therapeutic and preemptive DLI recipients were 16.7% and 33.3%, respectively. The occurrence of DLI-associated acute graft-versus-host disease predicted longer survival, whereas diagnosis of T cell acute lymphoblastic leukemia/lymphoma or myelodysplastic syndromes or early relapse after transplant (< 6 months) predicted shorter survival after therapeutic DLI. Cumulative incidence of progression to hematologic relapse and non-relapse mortality after preemptive DLI were 46.8% and 29.1%, respectively. Active disease prior to transplant and early molecular relapse after transplant (< 4 months) were the strongest predictors of non-relapse mortality after preemptive DLI. In conclusion, although therapeutic DLI had limited efficacy against T cell acute lymphoblastic leukemia/lymphoma or myelodysplastic syndromes or early post-transplant relapse, patients who developed DLI-associated acute graft-versus-host disease would benefit from this procedure in the setting of G-SCF-mobilized DLI. Furthermore, preemptive DLI could protect half of patients from hematologic relapse after transplantation with acceptable toxicity.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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