The DFTB theory was combined with the isothermal Brownian-type molecular dynamics (MD) and metadynamics molecular dynamics (MMD) algorithms to perform simulation studies for Au clusters. Two representative DFTB parametrizations were investigated. In one parametrization, the DFTB-A, the Slater-Koster parameters in the DFTB energy function were determined focusing on the ionic repulsive energy part, Erep and the other, the DFTB-B, due attention was paid to the electronic band-structure energy part, Eband . Minimized structures of these two parametrizations were separately applied in MD and MMD simulations to generate unbiased and biased trajectories in collective variable (CV) space, respectively. Here, we found the MD simulations monitored at 300 K manifest fluxional characteristics in planar cluster Au9 /DFTB-A, but give no discernible tracts of fluxionality for planar Au8 /DFTB-A and Au8 /DFTB-B, for nonplanar Au10 /DFTB-A and, to some extent, for nonplanar Au9 /DFTB-B; they are plausibly being hindered by higher-than kB T energy barriers. Very recent FIR-MPD spectroscopy measurements, however, were reported to have detected at 300 K both the planar and nonplanar neutral Aun clusters in the size range 5 ≤ n ≤ 13. The failure of MD simulations has prompted us to apply the MMD simulation and construct the free energy landscape (FEL) in CV space. Through scrutinizing the FELs of these clusters and their associated structures, we examine the relative importance of Erep /DFTB-A and Eband /DFTB-B in unraveling the covalent-like behavior of valence electrons in Aun . Most important of all, we shall evaluate the DFTB parametrization in MMD strategy through comparing extensively the simulation data recorded with the gas-phase experimental data. Monascus fermentation byproduct (MFB) is a biowaste generated after food colorants are extracted. Using MFB to produce probiotics (Bacillus subtilis) is a sustainable way for the entire production to be used as food or animal feed additives. However, due to the rigidity of the Monascus mycelium cell wall, B. subtilis cannot sufficiently utilize the nutrients in MFB, leading to low biomass production efficiency. We studied the effects of ultrasonic treatment, papain, β-glucanase, and chitosanase, and their combinations on improving the levels of soluble components from MFB. The effects of these treatments on mycelium cell walls were visualized using scanning electron microscopy, and their influence on B. subtilis production was analyzed. Ultrasonic treatment increased the soluble components by 210 g kg , including 50 g kg protein and 120 g kg carbohydrates. An enzyme mixture increased the soluble components by 160 g kg , including 30 g kg protein and 90 g kg carbohydrates. The combination of the two methods achieved the highest increase of soluble components (up to 400 g kg ) leading to a maximum B. subtilis production of 1 × 10 colony-forming unit mL . This yield was about 20 times greater than that using untreated MFB and about eight times greater than treatments using only ultrasonic or enzymatic methods. The productivity of B. subtilis production using MFB as the sole medium can be greatly improved by ultrasound or enzymes, which cause the release of intercellular components or cell wall components. © 2020 Society of Chemical Industry. The productivity of B. subtilis production using MFB as the sole medium can be greatly improved by ultrasound or enzymes, which cause the release of intercellular components or cell wall components. © 2020 Society of Chemical Industry.Hepatocellular carcinoma (HCC) is among the most common cancer types worldwide; yet, patients with HCC have limited treatment options. There is an urgent need to identify new drug targets that specifically inhibit the growth of HCC cells. Here, we used a newly-engineered CRISPR library targeting ~2,000 druggable genes to perform a high throughput screen, and identified adenylosuccinate lyase (ADSL) - a key enzyme involved in the de novo purine synthesis pathway - as a potential drug target for HCC. ADSL has been implicated as a potential oncogenic driver in some cancers, but its role in liver cancer progression remains unknown. CRISPR-mediated knockout of ADSL impaired colony formation of liver cancer cells by affecting adenosine monophosphate (AMP) production. In the absence of ADSL, the growth of liver tumors is retarded in vivo. Mechanistically, we found that ADSL knockout caused S-phase cell cycle arrest, not by inducing DNA damage, but by impairing mitochondrial function. Using HCC patient data, we also revealed that high ADSL expression occurs during tumorigenesis and is linked to poor survival rate. In conclusion, our findings uncover the role of ADSL-mediated de novo purine synthesis in fueling mitochondrial ATP production to promote liver cancer cell growth. https://www.selleckchem.com/products/gne-7883.html Targeting ADSL may be a therapeutic approach for HCC patients.Long-lived antibody-secreting plasma cells are essential to establish humoral memory against pathogens. While a regulatory transcription factor network has been established in plasma cell differentiation, the regulatory role of miRNAs remains enigmatic. We have recently identified miR-148a as the most abundant miRNA in primary mouse and human plasma cells. To determine whether this plasma cell signature miRNA controls the in vivo development of B cells into long-lived plasma cells, we established mice with genomic, conditional, and inducible deletions of miR-148a. The analysis of miR-148a-deficient mice revealed reduced serum Ig, decreased numbers of newly formed plasmablasts and reduced CD19-negative, CD93-positive long-lived plasma cells. Transcriptome and metabolic analysis revealed an impaired glucose uptake, a reduced oxidative phosphorylation-based energy metabolism, and an altered abundance of homing receptors CXCR3 (increase) and CXCR4 (reduction) in miR-148a-deficient plasma cells. These findings support the role of miR-148a as a positive regulator of the maintenance of long-lived plasma cells.Impinging/overriding dorsal spinous processes (DSPs) of the thoracolumbar vertebrae are a common cause of poor performance in horses. In the last five decades, numerous surgical treatments have been reported on, from transverse transection of the affected DSPs, and endoscopic resection of the affected DSPs, to transection of the interspinous ligament. Until recently, cosmetic outcomes have been reported as good to excellent in studies. However, a previously unreported complication of neurogenic atrophy of the contralateral epaxial muscle following desmotomy of the interspinous ligament has been recently reported. The authors hypothesised that this was because of a more lateral approach than previously described, resulting in the scissors being too far across midline and transecting a nerve in the region. Considering this finding, we have reviewed the literature on the neuroanatomy of the thoracolumbar region in the horse. Literature on the neuroanatomy of the horse is lacking when compared with that of humans and companion animals, with most of the work extrapolated from companion animals.