Baijiu (Chinese liquor) is a type of traditional distilled spirit drink produced by spontaneous fermentation. Lactic acid bacteria as the predominant bacteria during the fermentation of Baijiu may ...influence the flavor through the production of enzymes and metabolites. Results showed that there was significant difference in lactic acid bacteria counts between different fermentation periods. Indigenous lactic acid bacteria with high alcohol tolerance and esterase activity were selected for fortified fermentation. Inoculation with indigenous lactic acid bacteria significantly changed the flavor profile of Baijiu. All the selected strains promoted the formation of ethyl acetate which is an important flavor in Baijiu. Lactobacillus acetotolerans significantly promoted the formation of ethyl acetate, ethyl lactate, ethanol, acetic acid, and 2,4-di-tert-butylphenol. Sensory analysis revealed higher harmony in the samples fermented with L. hilgardii and L. acetotolerans, and higher intensive ester aroma in the samples fermented with L. planturum. The generation of flavors such as esters, alcohols and acids were species or even strain dependent. The results of this work will broaden our knowledge regarding the role of indigenous lactic acid bacteria during Baijiu manufacturing, and provide a potential approach for improving the flavor of Baijiu.
•Significant difference in lactic acid bacteria was found between two periods.•LAB strains with high alcohol tolerance and esterase activity were selected.•Flavour profile of Baijiu was significantly changed by selected LAB strains.•Lactobacillus acetotolerans promoted formation of ethyl acetate and ethyl lactate.
Met tyrosine kinase, a receptor for a hepatocyte growth factor (HGF), plays a critical role in tumor growth, metastasis, and drug resistance. Mitochondria are highly dynamic and undergo fission and ...fusion to maintain a functional mitochondrial network. Dysregulated mitochondrial dynamics are responsible for the progression and metastasis of many cancers. Here, using structured illumination microscopy (SIM) and high spatial and temporal resolution live cell imaging, we identified mitochondrial trafficking of receptor tyrosine kinase Met. The contacts between activated Met kinase and mitochondria formed dramatically, and an intact HGF/Met axis was necessary for dysregulated mitochondrial fission and cancer cell movements. Mechanically, we found that Met directly phosphorylated outer mitochondrial membrane protein Fis1 at Tyr38 (Fis1 pY38). Fis1 pY38 promoted mitochondrial fission by recruiting the mitochondrial fission GTPase dynamin-related protein-1 (Drp1) to mitochondria. Fragmented mitochondria fueled actin filament remodeling and lamellipodia or invadopodia formation to facilitate cell metastasis in hepatocellular carcinoma (HCC) cells both in vitro and in vivo. These findings reveal a novel and noncanonical pathway of Met receptor tyrosine kinase in the regulation of mitochondrial activities, which may provide a therapeutic target for metastatic HCC.
Improving both grain yield and resource use efficiencies simultaneously is a major challenge in rice production. However, few studies have focused on integrating dense planting with delayed and ...reduced nitrogen application to enhance grain yield, nitrogen use efficiency (NUE) and radiation use efficiency (RUE) in rice (Oryza sativa L.) in the double rice cropping system in South China. A high-yielding indica hybrid rice cultivar (Yliangyou 143) was grown in field experiments in Guangxi, South China, with three cultivation managements: farmers’ practice (FP), dense planting with equal N input and delayed N application (DPEN) and dense planting with reduced N input and delayed N application (DPRN). The grain yields of DPRN reached 10.6 and 9.78 t ha–1 in the early and late cropping seasons, respectively, which were significantly higher than the corresponding yields of FP by 23.9–29.9%. The grain yields in DPEN and DPRN were comparable. NUE in DPRN reached 65.2–72.9 kg kg–1, which was 61.2–74.1% higher than that in FP and 24.6–30.2% higher than that in DPEN. RUE in DPRN achieved 1.60–1.80 g MJ–1, which was 28.6–37.9% higher than that in FP. The productive tiller percentage in DPRN was 7.9–36.2% higher than that in DPEN. Increases in crop growth rate, leaf area duration, N uptake from panicle initiation to heading and enhancement of the apparent transformation ratio of dry weight from stems and leaf sheaths to panicles all contributed to higher grain yield and higher resource use efficiencies in DPRN. Correlation analysis revealed that the agronomic and physiological traits mentioned above were significantly and positively correlated with grain yield. Comparison trials carried out in Guangdong in 2018 and 2019 also showed that DPRN performed better than DPEN. We conclude that DPRN is a feasible approach for simultaneously increasing grain yield, NUE and RUE in the double rice cropping system in South China.
In most previous ice–ship interaction studies involving fluid effects, ice was taken as unbreakable. Building breakable level ice on water domain is still a big challenge in numerical simulation. ...This paper overcomes this difficulty and presents a numerical modeling of a ship moving in level ice on the water by using a one-way CFD-DEM (computational fluid dynamics-discrete element method) coupling method. The detailed numerical processes and techniques are introduced. The ice crack propagation process including radial and circular cracks have been observed. Numerical results are compared with previous experimental data and good agreement has been achieved. The results show that water resistance is an order of magnitude smaller than ice resistance during the ice-breaking process. Ice resistance shows strong oscillation along with ice failure process, which are affected by ship speed and ice thickness significantly.
To investigate the role of dexmedetomidine (DEX) in the inhibition of diabetic peripheral neuropathy (DPN) and the protection in the nerve damage.
Eighty male Sprague-Dawley (SD) rats were randomly ...allocated to four groups: the control group (C group), DPN model group (DPN group), DEX-treated group (DEX group), and the yohimbine treated group (YOH group). DPN was induced by intraperitoneal administration of streptozocin (STZ) (35 mg/kg). The body weights, blood glucose level, mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), the motor, and sensory nerve conduction velocities (MNCV and SNCV) of sciatic nerve were measured. Then the sciatic nerve was isolated for H&E staining and immunohistochemical staining. The oxidative stress makers such as malondialdehyde (MDA), superoxide-dismutase (SOD), and glutathione peroxidase (GSH-Px) and apoptosis related cytokines such as Bax, Bcl-2, and caspase-3 were estimated.
There was no significant difference of the blood glucose and body weight among the DPN group, DEX group, and YOH group. H&E staining showed that DEX treatment can ameliorate the damage of sciatic nerve cells. In the DPN group, MWT, TWL, MNCV, and SNCV were significantly reduced compared with the C group (P < 0.05). In DEX group rats, MWT, TWL, MNCV, and SNCV were increased significantly (P < 0.05) compared with the DPN group and YOH group rats. Lower SOD and GSH-Px, and higher MDA were found in the DPN group compared with the C group (P < 0.01), and DEX treatment restored SOD, GSH-px, and MDA activity significantly (P < 0.01). The expression levels of Bax and caspase-3 were increased, while that of Bcl-2 was decreased significantly in the DPN group compared with the C group (P < 0.05). In the DEX group, the expression levels of Bax and caspase-3 were decreased significantly (P < 0.05), while that of Bcl-2 was increased significantly (P < 0.05) compared with the DPN group and the YOH group.
The results of this study demonstrated that DEX has the inhibitory and protective effects on DPN of rats. This may be associated with its antioxidative and anti-apoptosis responses.
Polycomb repressor complex 1 (PRC1) is linked to the regulation of gene expression and histone ubiquitylation conformation, which contributes to carcinogenesis. However, the upstream regulators of ...PRC1 biogenesis machinery remain obscure. Here, we report that the polycomb group-related mammalian gene Mel18 is a target of the protein kinase AKT. AKT phosphorylates Mel18 at T334 to disrupt the interaction between Mel18 and other PRC1 members, leading to attenuated PRC1-dependent ubiquitylation of histone H2A at Lys119. As such, PRC1 target genes, many of which are known oncogenes, are derepressed upon T334-Mel18 phosphorylation, which promotes malignant behaviours, including cell proliferation, tumour formation, migration and invasion, bone and brain metastatic lesion formation. Notably, a positive correlation between AKT activity and pT334-Mel18 is observed, and prognostic models based on p-AKT and pT334-Mel18 that predicted overall survival and distant metastasis-free survival in breast cancer patients are established. These findings have implications for understanding the role of AKT and its associated proteins in chromatin ubiquitylation, and also indicate the AKT-Mel18-H2AK119ub axis as a novel prognostic biomarker and therapeutic target for cancer patients.
Koji-making is a key process for production of high quality soy sauce. The microbial composition during koji-making was investigated by culture-dependent and culture-independent methods to determine ...predominant bacterial and fungal populations. The culture-dependent methods used were direct culture and colony morphology observation, and PCR amplification of 16S/26S rDNA fragments followed by sequencing analysis. The culture-independent method was based on the analysis of 16S/26S rDNA clone libraries. There were differences between the results obtained by different methods. However, sufficient overlap existed between the different methods to identify potentially significant microbial groups. 16 and 20 different bacterial species were identified using culture-dependent and culture-independent methods, respectively. 7 species could be identified by both methods. The most predominant bacterial genera were Weissella and Staphylococcus. Both 6 different fungal species were identified using culture-dependent and culture-independent methods, respectively. Only 3 species could be identified by both sets of methods. The most predominant fungi were Aspergillus and Candida species. This work illustrated the importance of a comprehensive polyphasic approach in the analysis of microbial composition during soy sauce koji-making, the knowledge of which will enable further optimization of microbial composition and quality control of koji to upgrade Chinese traditional soy sauce product.
► The microbial composition during soy sauce koji-making was investigated. ► The most predominant bacterial genera were Weissella and Staphylococcus. ► The most predominant fungi were Aspergillus and Candida species.
More and more attention has been paid to research on variable geometry turbine engines with the increasing improvement of performance requirements for military turbines. Due to the fixed working ...angle of the inlet guide vane, the performance of a conventional fixed geometry turbine is optimal only for turbines near the design point. To match the aircraft's starting, climbing, cruising, deceleration, landing and other working states, it is necessary to change the turbine speed. This will not only reduce the performance of the turbine but also increase the fuel loss. The variable geometry turbine is a perfect solution to this problem. It is not necessary to change the speed of the turbine, but only the working angle of the inlet rotating guide vane of the turbine. The variable geometry turbine can be matched to each state of the aircraft's entire voyage. The turbine guide vane can be adjusted by 7° to bring about a 10% change in the flow rate of the entire machine. With constant turbine inlet temperature, the fuel loss can be effectively reduced. The rotating guide vane is impacted by the high-temperature and high-pressure gas and cold air in the inner culvert. Hot and cold air produce two types of aerodynamic torque on the rotating guide vane. There is also a friction torque on the rotating shaft of the guide vane. Therefore, the rotating guide vanes of variable geometry turbines are subjected to three types of torques. The main objective of this paper is to study three factors influencing the guide vane torque in the main flow path. The three influencing factors are the turbulence intensity of the gas, the flow ratio of cold gas to hot gas and the location distribution of the gas film holes on the guide vane. In this paper, CFD temperature-fluid-solid coupling algorithm combined with UDF program is applied to solve the torque of guide vane shaft at three influencing factors. The results show that the three factors, turbulence intensity, flow ratio and air film hole distribution, can have a significant effect on the guide vane torque. This is of great significance for the research and design of variable geometry turbines.
The aim of this study was to evaluate the diagnostic value of the Score for the Targeting of Atrial Fibrillation (STAF) in combination with the serum D-dimer (DD) levels in cardioembolism(CE).This ...study was a retrospective case-onlystudy, consecutively including patients with acute ischemic stroke. All patients were evaluated following the STAF scoring criteria and were classified according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) etiology classification criteria. A total of 317 patients were enrolled, including 37 CE cases (11.67%). STAF ≥5 showed a sensitivity of 89% and a specificity of 91% for the diagnosis of CE, whereas DD >791.30 ng/mL had a sensitivity of 58% and a specificity of 78%. When the STAF was used in combination with the DD level, the sensitivity was 95%, and the specificity was 100%.STAF score is an excellent tool for the diagnosis of CE when combined with DD, and can facilitate the etiological classification of acute ischemic stroke.
Advanced nasopharyngeal carcinoma (NPC) is an aggressive disease with no targeted therapies and poor outcomes. New innovative targets are urgently needed. KLF4 has been extensively studied in the ...context of tumors, and current data suggest that it can act as either a tissue-specific tumor-inhibiting or a tumor-promoting gene. Here, we found that KLF4 played as a tumor-promoting gene in NPC, and could be mediated by PLK1.
Tissue immunohistochemistry (IHC) assay was performed to identify the role of KLF4 in NPC. Global gene expression experiments were performed to explore the molecular mechanisms underlying KLF4-dependent tumorigenesis. Small-molecule kinase inhibitor screening was performed to identify potential upstream kinases of KLF4. The pharmacologic activity of polo-like kinase inhibitor volasertib (BI6727)
and
was determined.
Our investigation showed that high expression of KLF4 was correlated with poor prognosis in NPC. Moreover, genome-wide profiling revealed that KLF4 directly activated oncogenic programmes, including gene sets associated with KRAS, VEGF, and MYC signalling. We further found that inhibition of polo-like kinase 1 could downregulate the expression of KLF4 and that PLK1 directly phosphorylated KLF4 at Ser234. Notably, phosphorylation of KLF4 by PLK1 caused the recruitment and binding of the E3 ligase TRAF6, which resulted in KLF4 K32 K63-linked ubiquitination and stabilization. Moreover, KLF4 could enhance TRAF6 expression at the transcriptional level, thus initiating a KLF4-TRAF6 feed-forward loop. Treatment with the PLK1 inhibitor volasertib (BI6727) significantly inhibited tumor growth in nude mice.
Our study unveiled a new PLK1-TRAF6-KLF4 feed-forward loop. The resulting increase in KLF4 ubiquitination leads to stabilization and upregulation of KLF4, which leads to tumorigenesis in NPC. These results expand our understanding of the role of KLF4 in NPC and validate PLK1 inhibitors as potential therapeutic agents for NPC, especially cancer patients with KLF4 overexpression.
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