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What Is Known and Objective. CYP2C19 is an important influencing factor for voriconazole trough plasma concentration (Cmin); however, it is not verified in Child–Pugh C (CP-C) cirrhosis patients, and no voriconazole dosage regimen is recommended for these patients in the package insert. This retrospective study identified CYP2C19 and other factors influencing voriconazole Cmin for CP-C cirrhosis, and obtained an appropriate method of application of voriconazole for them. Methods. A total of 66 patients with CP-C cirrhosis who accepted voriconazole therapy were involved. The voriconazole Cmin, clinical characteristics, CYP2C19 genotype, and adverse effects (AEs) were recorded and analyzed. Results. Unlike other research studies, voriconazole Cmin was not different among normal metabolizers (NMs), intermediate metabolizers (IMs), and poor metabolizers (PMs) of the CYP2C19 enzyme in CP-C cirrhosis (P > 0.05). The maintenance dose regimen for voriconazole was the only independent influencing factor for Cmin (P = 0.045; OR = 3.753; 95% CI, 1.029–13.694). At about 1/3 of the recommended maintenance dose, only 16.7% (8/48) had Cmin >5.5 μg/mL, 4.5% (3/48) had Cmin <1 μg/mL, and only one AE happened. There were four voriconazole-related AEs that happened in this study, and three AEs occurred (3/4, 75%) when the maintenance dose was not adjusted with therapeutic drug monitoring (TDM). What Is New and Conclusion. Voriconazole Cmin did not significantly vary according to CYP2C19 enzyme metabolization status (being an NM, IM, or PM) in CP-C cirrhosis. Reducing the maintenance dose of voriconazole to approximately 1/3 the standard maintenance dose and administering in combination with TDM in patients with CP-C cirrhosis are recommended. [ABSTRACT FROM AUTHOR]

Background. Hepatocellular carcinoma (HCC) is a very common malignant tumor. Long noncoding RNAs (lncRNAs) enable discoveries of new therapeutic tumor targets. We aimed to study the role and potential regulatory mechanisms of the lncRNA KIF9-AS1 in HCC. Methods. CCK-8, scratch assay, and flow cytometry were used to detect cell proliferation, migration, and apoptosis, respectively. Bax, Bcl-2, ERK, and pERK expression were measured by western blotting. StarBase predicted KIF9-AS1 expression in HCC and paracancerous tissues. RPISeq predicted the interaction score of KIF9-AS1 and DNMT1, and MethyPrimer revealed the CpG island distribution in the RAI2 promoter. MSP was performed to measure RAI2 methylation. RIP and ChIP were performed to examine lncRNA KIF9-AS1, DNMT1, and RAI2 interactions. Finally, the effect of KIF9-AS1 knockdown on HCC was verified with nude mice. Results. We found that KIF9-AS1 expression was increased in HCC tissues. KIF9-AS1 knockdown inhibited the proliferation and migration, and facilitated the apoptosis of HCC cells. lncRNA KIF9-AS1-mediated RAI2 expression led to DNMT1 recruitment and regulated RAI2 DNA methylation. RAI2 overexpression inhibited the proliferation and migration and promoted the apoptosis of HCC cells. KIF9-AS1 knockdown inhibited subcutaneous tumor formation in vivo. Conclusion. This study shows that KIF9-AS1 accelerates HCC growth by inducing DNMT1 promotion of RAI2 DNA methylation. [ABSTRACT FROM AUTHOR]

The Prototethyan Ocean has been suggested as an Early Paleozoic Ocean developed at the Gondwana northern margin. However, its spatial pattern, subduction style and closure time in SW Yunnan and SE Asia still remain unknown. The Prototethyan evolution in SW Yunnan and SE Asia and its internal connection with the South China Kwangsian (Ordo-Silurian) intracontinental orogenesis are also poorly constrained. By summarizing and analyzing the Early Paleozoic geological records in the Sibumasu and Indochina blocks, the eastern South China and SW Japan, this paper proposes the existence of a giant Ordo-Silurian igneous belt along the Gondwana northern margin. A preliminary limitation has been obtained regarding the source nature and migration pattern of the igneous belt. Our data allow us to propose a model of the Early Paleozoic Andean-type active continental margin along the East Gondwana northern margin. This is the foundation to determine the southward subduction of the southern branch of the eastern Prototethyan Ocean underneath the Sibumasu and Indochina blocks along the Yunxian-Menghai (SW Yunnan)-Thailand Peninsula and the Tam Ky-Phouc Son suture in Central Vietnam, respectively, and the eastward linkage with the Early Paleozoic Osaka subduction zone in SW Japan across the peripheral Sanya area. These data synthetically indicate an easterly-diachronous and propagating Andean-type Cambrian (Furongian)-Silurian (Llandovery) orogenesis along the Gondwana northern margin from Nepal, NW India, South Tibet, Qiangtang to Central Vietnam across South Indochina and Sibumasu. This paper reconstructs the Early Paleozoic locations of the Sibumasu and Indochina fragments, as well as SW Japan and South China continent in the Gondwana northern margin, and proposes the far-field effect on the South China Kwangsian intra-continental orogenesis from the subduction of the Early Paleozoic Prototethyan southern branch. [ABSTRACT FROM AUTHOR]

Montmorillonite (MMT) is widely used as the catalyst in the commercial production of dimeric fatty acids (DAs). However, the dimerization activity of MMTs from different mineral sources is usually different, leading to unstable yield of DAs. In order to obtain a high and stable yield of DAs, the relationship between the dimerization activity and characteristics of MMT should be clarified. The characteristics of seven MMTs from different mineral sources, including the acidity (the type, strength, and amount of the acid sites), composition (interlayer cations, Si/Al ratio, water content, pH), and structure (basal spacing) are determined and correlated with their dimerization activity. Additionally, the relationship between dimerization activity and characteristics of MMT is quantified by nonlinear‐regression. It is found that the dimerization activity of MMT is mainly influenced by its Brønsted acidity and basal spacing. Stable DA yield of around 70% on MMT is obtained at the amount of weak Brønsted acid sites of more than 0.20 mmol g−1 and basal spacing of larger than 1.50 nm. Additionally, it is found that acid treatment is an effective method to adjust the Brønsted acidity and basal spacing of MMT. Practical Applications: The positive effect of Brønsted acid sites amount and basal spacing on the activity of MMT has practical value on the selection of highly efficient MMT catalyst for DA production. In addition, some MMT with poor activity can be activated by the acid treatment method mentioned in the paper. [ABSTRACT FROM AUTHOR]

Methyl linolenate (C18-3) is a type of unsaturated fatty acid methyl ester with high biological activity. Membrane separation of C18-3 from tallow seed oil methyl ester by supported ionic liquids membranes (SILM) containing carrier Ag+ was successfully achieved in this study. The interaction between Ag+ and C18-3 was explored by density functional theory (DFT). High selectivity to C18-3 was mainly due to the π/inverse π complexation interactions between Ag+ and C=C bonds. The effects of ionic liquid structure, carrier Ag+ concentration, adjacent phase flow rates and membrane pore size on permeability and selectivity to C18-3 were examined. The existence of 1-hexene in the stripping phase and carrier Ag+ can facilitate C18-3 transport. Good separation performance was achieved by the 0.45 μm nylon membrane impregnated with ionic liquid [BMIm]BF 4 containing AgBF 4. C18-3 was enriched from 16.7% in the feed phase to higher than 75% in the product. Moreover, adding a hydrophobic PVDF protective membrane to form a composite membrane was an effective method to increase the SILM stability and membrane lifetime by about twice compared with a single nylon membrane. • Ag+-based supported ionic liquid membrane was used to separate methyl linolenate.. • The action mechanism between Ag+ and methyl linolenate was explored by DFT. • Ag+ preferentially coordinated with C=C bond rather than C=O bond. • Hydrophilic/hydrophobic composite membrane could improve the membrane stability. • 1-hexene in the stripping phase and Ag+ can facilitate methyl linolenate transport. [ABSTRACT FROM AUTHOR]

The creation of a catalytic method that possesses high activity and effective reusability for the oxidative cleavage of vegetable oils and their derivatives to prepare bio-based oxo-chemicals is a challenge. This work introduces a “release and capture” catalytic system consisting of H2O2, WO3 and mesoporous SnO2. This system was intended to promote catalyst reusability in the oxidative cleavage of methyl 9,10-epoxystearate (ME) to the corresponding aldehydes. No organic solvent was used in the reaction. The reaction temperature, molar ratio of ME/WO3/H2O2, and reaction time were optimized to 70 °C, 1/0.017/1.3, and 20 min, respectively. Under these conditions, complete ME conversion and 80% aldehyde yield were obtained. The hot filtration experiment and ICP-MS analysis confirmed the leaching of tungsten. Mesoporous SnO2 did not affect the ME conversion and aldehyde yield, but effectively adsorbed the leached tungsten. The catalyst in this system showed no significant decrease in activity after being reused ten times. [ABSTRACT FROM AUTHOR]

At present, the utilization of grease has attracted more and more attention. This article presents a simple method that efficiently cleaves methyl oleate‐derived methyl 9,10‐epoxystearate (a) to give high yields of methyl 9‐oxononanoate (d) with nonanal (c) as co‐product. A WO3/MCM‐41 catalyst is prepared via direct mixed‐gel synthesis. The catalyst is tested in the oxidative cleavage of a to produce d which can be used as a polymer precursor or an important feedstock. The effects of WO3 loading, temperature, time, H2O2/a molar ratio, catalyst/a weight ratio, and t‐BuOH/a weight ratio on the a conversion and d yield are examined using single‐factor experiments. The optimal reaction conditions are determined by orthogonal experiments. The optimal WO3 loading, temperature, time, H2O2/a molar ratio, catalyst/a weight ratio, and t‐BuOH/a weight ratio are 35%, 80 °C, 20 min, 1.3, 0.04, and 0.5, respectively. Under these conditions, the a conversion and d yield reach 99.4 and 78.4%, respectively. In addition, the catalyst shows no significant decrease in activity after being reused three times. Moreover, the reaction mechanism is studied based on the product distribution over time. Practical Applications: Few studies on methyl 9,10‐epoxystearate used as the raw material to give methyl 9‐oxononanoate and nonanal are found. Because the ethylene oxide bond is more unstable than the carbon–carbon double bond, the oxidative cleavage of methyl 9,10‐epoxystearate is easier than cleavage of methyl oleate that allows the oxidative cleavage to be done under milder conditions. Methyl 9‐oxononanoate can be converted to a monomer of high‐value polymers and is also an important feedstock in the production of chemicals. The co‐product nonanal is a natural spice which can be used in the fragrance industry. The results show that the reaction time is short and methyl 9‐oxononanoate yield is high under mild reaction conditions. The method in this study can also be widely used in other oxidative cleavage reactions of epoxides. Methyl 9,10‐epoxystearate is used as the raw material to produce methyl 9‐oxononanoate with nonanal as co‐product using WO3/MCM‐41 as catalyst and H2O2 as oxidant. [ABSTRACT FROM AUTHOR]

A novel amphiphilic derivative of chitosan, namely, a linoleic acid-g-quaternary chitosan (LA-g-QC), was designed and synthesized as low toxic material for biomedical applications in this study. The chemical structure of LA-g-QC was characterized by Fourier transform infrared spectroscopy (FTIR), 1H nuclear magnetic resonance (1H-NMR), and elemental analysis. LA-g-QC could form nanosized micelles with self-assembly, which was confirmed by the results of critical micelle concentration (CMC) via fluorescence spectroscopy. The average size of LA-g-QC was 140 nm and its zeta potential was approximately +35.50 mV. CMC value was 31.00 mg/mL. Furthermore, LA-g-QC micelles, at final concentrations between 0.94 μg/mL and 30 μg/mL, did not inhibit the proliferation of HepG2 or SMMC 7721 cell lines. Taken together, LA-g-QC has low cytotoxicity and high potential for the preparation of novel drug-delivery micelles. [ABSTRACT FROM AUTHOR]

Extensive research focused on finding effective strategies to prevent or improve recovery from myocardial ischaemia/reperfusion (I/R) injury. Basic fibroblast growth factor (b FGF) has been shown to have therapeutic potential in some heart disorders, including ischaemic injury. In this study, we demonstrate that b FGF administration can inhibit the endoplasmic reticulum ( ER) stress and mitochondrial dysfunction induced in the heart in a mouse model of I/R injury. In vitro, b FGF exerts a protective effect by inhibiting the ER stress response and mitochondrial dysfunction proteins that are induced by tert-Butyl hydroperoxide ( TBHP) treatment. Both of these in vivo and in vitro effects are related to the activation of two downstream signalling pathways, PI3K/Akt and ERK1/2. Inhibition of these PI3K/Akt and ERK1/2 pathways by specific inhibitors, LY294002 and PD98059, partially reduces the protective effect of b FGF. Taken together, our results indicate that the cardioprotective role of b FGF involves the suppression of ER stress and mitochondrial dysfunction in ischaemic oxidative damage models and oxidative stress-induced H9C2 cell injury; furthermore, these effects underlie the activation of the PI3K/Akt and ERK1/2 signalling pathways. [ABSTRACT FROM AUTHOR]

A novel fluorescence detection method for phosphoproteins in 1-D and 2-D SDS-PAGE by using purpurin is developed in this study. Phosphoproteins as low as 4–8 ng could be specifically detected by purpurin within 60 min, and the detection limit is similar to or better than that of Pro-Q Diamond staining. Only 2 steps (staining and destaining) are needed for purpurin staining without requiring excessive fixing and washing steps, and for single use, $0.8 is enough for purpurin staining. By comprehensively comparing with Pro-Q Diamond staining, it is concluded that purpurin staining is a simple, rapid and low-cost staining method for a broad application to the research of phosphoproteins. [ABSTRACT FROM AUTHOR]

Paraspeckle protein 1 (PSPC1) was first identified as a structural protein of the subnuclear structure termed paraspeckle. However, the exact physiological functions of PSPC1 are still largely unknown. Previously, using a proteomic approach, we have shown that exposure to cisplatin can induce PSPC1 expression in HeLa cells, indicating the possible involvement for PSPC1 in the DNA damage response (DDR). In the current study, the role of PSPC1 in DDR was examined. First, it was found that cisplatin treatment could indeed induce the expression of PSPC1 protein. Abolishing PSPC1 expression by siRNA significantly inhibited cell growth, caused spontaneous cell death, and increased DNA damage. However, PSPC1 did not co-localize with γH2AX, 53BP1, or Rad51, indicating no direct involvement in DNA repair pathways mediated by these molecules. Interestingly, knockdown of PSPC1 disrupted the normal cell cycle distribution, with more cells entering the G2/M phase. Furthermore, while cisplatin induced G1/S arrest in HeLa cells, knockdown of PSPC1 caused cells to escape the G1/S checkpoint and enter mitosis, and resulted in more cell death. Taken together, these observations indicate a new role for PSPC1 in maintaining genome integrity during the DDR, particularly in the G1/S checkpoint. [ABSTRACT FROM AUTHOR]

Abstract: Cisplatin has been widely accepted as one of the most efficient anticancer drugs for decades. However, the mechanisms for the cytotoxic effects of cisplatin are still not fully understood. Cisplatin primarily targets DNA, resulting in the formation of DNA double strand breaks and eventually causing cell death. In this study, we applied two-dimensional electrophoresis coupled with LC–MS/MS to analyze the nuclear proteome of HeLa cells treated with cisplatin, in an effort to uncover new mechanistic clues regarding the cellular response to cisplatin. A total of 19 proteins were successfully identified, and these proteins are involved in a variety of basal metabolic and biological processes in cells, including biosynthesis, cell cycle, glycolysis and apoptosis. Six were related to the regulation of mRNA splicing, and we therefore asked whether the Fas gene might undergo alternative splicing following cisplatin treatment. This proved to be the case, as the splicing forms of Fas were modified in cisplatin-treated HeLa cells. This work provides novel information, from the perspective of the nuclear response, for understanding the cytotoxicity caused by cisplatin-induced DNA damage. [Copyright &y& Elsevier]