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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

The Kuching zone in NW Kalimantan and Malaysia Sarawak might be the southerly-extending segment of the paleo-Pacific subduction that is developed along the Coastal South China and SE Vietnam, and separated the Sundaland “old-land” from the Cenozoic Sibu zone. However, establishing this link is hindered by the lack of data on the Mesozoic orogenic history in NW Kalimantan. This paper presents zircon U-Pb geochronological and Hf-O isotopic data as well as whole-rock elemental and Sr-Nd-Pb isotopic results for the Raya Volcanics and their equivalents, as well as the Mensibau batholith in NW Kalimantan. The Raya Volcanics and Mensibau granitoids formed at 130–144 Ma, synchronous with the Menunuk Volcanics, but significantly older than the Pakong-Serabang mafic rocks and Serian Volcanics (~77–98 Ma) in the Sarawak Kuching zone. The Raya Volcanics and their equivalents belong compositionally to tholeiitic to low-K calc-alkaline series, and exhibit “spiky” PM-normalized patterns with Nb/La = 0.16–0.32, (87Sr/86Sr)i = 0.70187–0.70671 and eNd(t) = +0.9 to +3.6. Their (206Pb/204Pb)i, (208Pb/204Pb)i and (207Pb/204Pb)i range from 18.49 to 18.83, 38.39 to 39.19 and 15.57 to 15.70, and zircon eHf(t)-δ18O values from +4.1 to +16.1, and 5.21‰ to 6.05‰, respectively. They are derived from mantle wedge modified by recycled sediments. The Mensibau batholith is dominated by I-type granodiorite and granite. They share similar elemental ratios and Sr-Nd-Pb-Hf-O isotopic compositions with the Raya Volcanics, and originated from wedge-derived juvenile mafic crust. The temporal-spatial and geochemical accordance for the Raya Volcanics and Mensibau batholith document the extensive development of the early Cretaceous igneous rocks in NW Kalimantan. The Kuching zone is a northeasterly-propagated Cretaceous accretionary system that developed in response to the subduction of the paleo-Pacific plate.

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.

A novel silver-based dihydric alcohol extractant was substituted for ionic liquids to enrich methyl linolenate (C18-3) from tallow seed oil methyl ester in this study. The interactions among dihydric alcohol, Ag(I) and C18-3 were explored by FT-IR spectroscopy. The effects of dihydric alcohol structure, carrier Ag(I) concentration, temperature and initial feed concentration on extraction yield and selectivity were reported. The good extraction performance was achieved by 1,4-butanediol containing AgBF4. The complexation of Ag(I) with C18-3 was dominant in extraction operation rather than physical partition. Furthermore, a multi-step reverse extraction method was proposed to obtain C18-3 product and regenerate the extractant. 1-Hexene as the stripping phase can facilitate C18-3 reverse extraction. The content of C18-3 in the product was up to 93.36%, and the yield was 73.76%. This work opened a new route for the utilization of the dihydric alcohol properties to manipulate the carrier efficiency for extracting unsaturated fatty acid methyl esters at a lower cost.

The volcanic rocks in the Chanthaburi zone are rarely reported, but are important in investigating the tectonic evolution of the Palaeotethyan Ocean in SE Thailand. Four rhyolitic samples from Ko Chang Island yield zircon ages of 258–254 Ma, confirming the presence of Late Permian volcanic rocks in SE Thailand. These rocks consist of Group 1 rhyolites and Group 2 rhyolitic ignimbrites and have high K2O contents of 4.92–7.10 wt% and A/CNK values of 1.10–1.69. They are enriched in the light rare earth elements, Rb, Th, U, Zr and Y and show negative anomalies of Ba, Sr, Nb, Ta and Ti, with clear Eu anomalies. Their whole-rock eNd (t) values range from −1.7 to −3.1. Zircon in situ eHf (t) and δ18O values range from 0.0 to +5.6 and from 8.2 to 9.6‰, respectively. They belong to the group of peraluminous, ultrapotassic A-type rhyolites and were derived from partial melting of a mixed source of Mesoproterozoic metasedimentary rocks with a component of juvenile mafic crust. These ultrapotassic rhyolites formed in a continental rift setting in response to the rollback of a subducted Palaeotethyan oceanic slab beneath the Indochina Block. Combining these results with previous geological observations, we propose that there were some sporadically distributed continental rift basins along the Eastern Palaeotethyan domain during the Permian. Supplementary material: Major oxides, trace element analytical and Nd isotopic data, LA–ICP–MS and SIMS zircon U–Pb ages and Zircon in-situ Hf–O isotopic compositions are available at https://doi.org/10.6084/m9.figshare.c.5635390

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]BF4 containing AgBF4. 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.

An innovative ball-mill reactor was designed and made to produce dimer acid continuously. Mixing and polymerization in the constructed reactor were intensified by the rotation of the cylinder and mechanical actions of small beads. A total of 3 baffles were set up to enhance radial turbulence, and 10 clapboards were sequentially installed to separate the whole reactor into 11 small reactors in series in order to make it close to a plug-flow reactor. The relationship between reaction performance and the inner components (baffles and clapboards), ball-milling medium, rotating speed, wall temperature and residence time were investigated. The crude product containing 50.6% dimer acid was obtained under the optimal conditions (zirconia beads as ball-milling medium, wall temperature 300 °C, residence time 2.16 h, rotating speed 20 rpm). Ferric and nickel ion from the reactor and the uneven residence time distribution resulted in low dimer acid production yield.

Methyl linolenate was separated from its analogues by a new extraction system constructed by solvent, imidazolium based ionic liquids and cuprous salt. Firstly, the effect of ionic liquid on the dissolution of CuCl in acetonitrile, N,N-dimethylformamide (DMF), methanol and water was evaluated by visual observation. [C4Mim][Cl] can improve the dissolution of CuCl in acetonitrile. Then, for the new system as acetonitrile-ILs-CuCl, extraction equilibrium, distribution ratio and selectivity of methyl linolenate and its analogues were determined by gas chromatography analysis and the mass balance. The extraction time, IL structures and CuCl concentrations were investigated. Distribution ratio decreased slightly, but selectivity increased significantly with the addition of CuCl, [C4Mim][Cl] or [C4Vim][NTF2] into acetonitrile. [C4Vim][NTF2] had higher selectivity than [C4Mim][Cl]. But the selectivity of the system combining CuCl with [C4Vim][NTF2] was much lower than with [C4Mim][Cl]. For the CuCl-[C4Mim][Cl]-acetonitrile, the extraction efficiency was better than CuCl-acetonitrile, increasing Cu+ concentration effectively improved the separation selectivity when ratio of CuCl/[C4Mim][Cl] was less than 1. Compared with previous aqueous AgNO3 extractions, the method of using CuCl is a much cheaper and practical way to enrich unsaturated fatty acid.

Supported liquid membranes show great potential in the efficient separation of methyl linolenate from its analogues, but there still remain some critical challenges to further this technology towards larger application because of the slow transmembrane transport and poor stability of liquid membrane. Herein, 1,2-butanediol (1,2-BDO) with good solubility for AgBF4 substitutes for ionic liquid as membrane solvent, and fabric reinforced hollow fiber composite membrane (PR-HFM) with higher mechanical strength and interfacial area replaces plate membrane as base support. A new supported liquid membrane has been prepared by coating the 1,2-BDO solution dissolving AgBF4 on the surface of PR-HFM and embedding the solution into the micro-pores of PR-HFM by repeated pull with vacuum and push with N2. The as-prepared liquid membranes exhibit good separation performance and stability. It can be safely and steadily used to treat the feed with fatty acid methyl esters (FAMEs) concentration lower than 150 mg/mL at the velocity of less than 0.22 m/s. Within 24 h continuous operation, methyl linolenate (C18-3) can pass steadily through the liquid membrane at the mean permeability larger than 3.13 × 10−7 m/s, the C18-3 product with the purity larger than 82% and the selectivity of C18-3 over C18-2 (SC18-3/C18-2) larger than 6.63 can be obtained steadily.

Oleaginous biomass conversion to liquid hydrocarbon biofuels has emerged as an effective solution to the energy crisis and environmental problems. In this process, the removal of oxygenated compounds will directly affect the effectiveness of subsequent biofuel applications. Herein, deoxygenation of oleic acid by catalytic cracking was conducted using five various elements (La, Ni, P, Zr and Ce) modified Al-MCM-41. The related characterizations were carried out for these catalysts, including N2 physisorption, XRD, XPS, pyridine-FTIR and NH3-TPD techniques. The results showed the mesoporous structure of Al-MCM-41 was maintained after different modifications, and these catalysts greatly improved the hydrocarbons content and physiochemical properties of biofuels. The modified catalysts tended to facilitate the decarbonylation pathway and showed high selectivity to alkane and aromatic hydrocarbons. Besides, La/Al-MCM-41 presented excellent anti-coking activity. Ni/Al-MCM-41 showed both high dehydrogenation and deoxygenation activities. The Zr modification and Ce modification had a promotion effect in the deoxidizing activity of the catalyst, owing to the formation of oxophilic metal oxides. Noteworthily, P/Al-MCM-41 displayed the best deoxidizing performance due to its high Bronsted acidity, which caused the highest hydrocarbons content (82.30 %) and the lowest fatty acids content (around 0 %) of the biofuel. Moreover, the resulting biofuel had not only low oxygen content (3.88 wt.%) and acid value (5.47 mgKOH g−1) but also a high calorific value (44.50 MJ kg−1), which could be processed into green diesel. Hence, the catalytic cracking of fatty acid over P/Al-MCM-41 has excellent potential to produce high-quality renewable fuels.

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 Bronsted acidity and basal spacing. Stable DA yield of around 70% on MMT is obtained at the amount of weak Bronsted 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 Bronsted acidity and basal spacing of MMT. Practical Applications: The positive effect of Bronsted 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.

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.

An accurate and validated liquid chromatography method and a triple quadrupole mass spectrometry method were developed and validated to simultaneously evaluate the cytochrome P450 (CYP) enzymes in vivo using the co-administration of these probes. Phenacetin, losartan, metoprolol and midazolam were used as the probe substrates for rat CYP1A2, CYP2C11, CYP2D4 and CYP3A1 enzymes, respectively. The purpose of the study was to investigate the effect of apatinib on these cytochrome P450 enzymes in vivo with co-administration of these probes. Plasma samples were prepared by precipitating protein with acetonitrile. The analytes were separated using a reversed-phase BEH C18 column (2.1mm×100mm, 1.7μm, Waters, USA) maintained at 40°C. The mobile phase consisted of acetonitrile and water (containing 0.1% formic acid) with a gradient elution pumped at a flow rate of 0.4mL/min. The analytes were detected with positive electrospray ionization in multiple reaction monitoring (MRM) mode for target fragment ions m/z 180.05→109.94 for phenacetin, m/z 423.1→207.2 for losartan, m/z 268.12→115.8 for metoprolol, m/z 326.02→290.99 for midazolam and m/z 285.1→193.1 for diazepam (IS). Good linearity was achieved to quantify the concentration ranges of 10-2000ng/mL for phenacetin, 10-1000ng/mL for losartan, 10-1000ng/mL for metoprolol and 1-100ng/mL for midazolam in rat plasma. The mean recoveries of phenacetin, losartan, midazolam and metoprolol from the plasma exceeded 77.07%. The intra-run and inter-run assay precisions were both less than 8.9%. This method was successfully applied to evaluate the effects of apatinib on the cytochrome P450 enzymes in rats.

Lithium–sulfur (Li–S) battery is one of the most attractive candidates for the next-generation energy storage system. However, the intrinsic insulating nature of sulfur and the notorious polysulfide shuttle are the major obstacles, which hinder the commercial application of Li–S battery. Confining sulfur into conductive porous carbon matrices with designed polarized surfaces is regarded as a promising and effective strategy to overcome above issues. Herein, we propose to use microalgaes (Schizochytrium sp.) as low-cost, renewable carbon/nitrogen precursors and biological templates to synthesize N-doped porous carbon microspheres (NPCMs). These rational designed NPCMs can not only render the sulfur-loaded NPCMs (NPCSMs) composites with high electronic conductivity and sulfur content, but also greatly suppress the diffusion of polysulfides by strongly physical and chemical adsorptions. As a result, NPCSMs cathode demonstrates a superior reversible capacity (1030.7 mA h g–1) and remarkable capacity retention...

DNA-damaging agents have been reported to be associated with cardiovascular complications, however, the underlying mechanisms remain to be clarified. In the present study, the possible vascular effects of cisplatin was assessed by measuring its effects on the contractile function of thoracic aortic rings dissected from Sprague-Dawley (SD) rats. Contraction of the aortic ring was induced by 60 mM KCl or 10−6 M phenylephrine (PE) in an ex vivo perfusion system. Cisplatin (200 μM) counteracted KCl- and PE-induced contraction by 57.6 and 91.8%, respectively, in endothelium-intact aortic rings. Similar results were obtained in endothelium-denuded aortas. Electromicroscopy analysis revealed severe damage to blood vessel walls in vivo by cisplatin. In addition, cisplatin significantly inhibited adenosine triphosphate (ATP)-induced intracellular Ca2+ concentration ([Ca2+]i) increases in human umbilical vein endothelial cells (HUVECs). These results suggested that the DNA-damaging agent cisplatin can affect the contractile function of thoracic aortas. In addition, in accordance with its DNA-damaging properties, the cardiovascular toxicity of cisplatin may be the result of its direct cytotoxicity.

Pseudomonas aeruginosa produces multiple virulence factors that have been associated with quorum sensing. The aim of this study was to evaluate the prevalence of drug resistant profiles and quorum sensing related virulence factors. Pseudomonas aeruginosa were collected from different patients hospitalized in China, the isolates were tested for their susceptibility to different common antimicrobial drugs and detected QS-related virulence factors. We identified 170 isolates displaying impaired phenotypic activity, approximately 80 % of the isolates were found to exhibit the QS-dependent phenotypes, among them, 12 isolates were defective in AHLs production, and therefore considered QS-deficient strains. Resistance was most often observed to Cefazolin (81.2 %), followed by trimethoprim-sulfamethoxazole (73.5 %), ceftriaxone (62.4 %) and Cefotaxime, Levofloxacin, Ciprofloxacin (58.8 %), and to a lesser extent Meropenem (20.0 %), Cefepime (18.8 %), and Cefoperazone/sulbactam (2.4 %) The QS-deficient isolates that were negative for virulence factor production were generally less susceptible to the antimicrobials. The results showed a high incidences of antibiotic resistance and virulence properties in P. aeruginosa, and indicate that the clinical use of QS-inhibitory drugs that appear superior to conventional antimicrobials by not exerting any selective pressure on resistant strains.

Using a proteomic approach, we have previously shown that exposure to different concentrations of cisplatin during a 12-h period can lead to changes in nuclear protein expression and alternative splicing in HeLa cells. To further shed light on the DNA damage response (DDR) induced by cisplatin, we examined the nuclear proteome profiles of HeLa cells treated with 5μM cisplatin for different times (2, 12, and 24h). Two-dimensional electrophoresis (2-DE) identified 98 differentially expressed proteins in cisplatin-treated cells as compared to control cells. Among them, 54 spots (55%) were down-regulated and 44 spots (45%) were up-regulated. 51 spots were subjected to Matrix-assisted-laser-desorption-ionization Time-of-flight/time-of-flight Mass spectrometry (MALDI-TOF/TOF MS) identification, and 40 spots were identified. Among these, 22 proteins were located in nucleus. These proteins were involved in stress response, cell cycle and division, apoptosis, mRNA processing, transport, splicing and microRNA (miRNA) maturation. The changed expression of Annexin A1 and Lamin B1 were confirmed by Western blot. The role of Annexin A1 in the response to cisplatin-induced DNA damage was further analyzed, and it was shown that after Annexin A1 knockdown, cisplatin-induced DNA damage was significantly increased. In addition, the changed expression of several miRNAs was also observed by quantitative real-time PCR (qRT-PCR). Taken together, these data indicate that cisplatin-induced DDR is a complex process, and that those proteins identified by proteomics can lead to new directions for a better understanding of this process.

The effects of pulse ultrasound with different pulse parameters on the breakthrough curves of Geniposide on Resin 1300 were studied. The mass transfer model describing the adsorption process was constructed. Adsorption capability and the overall mass-transfer coefficient were obtained by fitting the constructed mass-transfer model and the experimental data. The effects of pulse ultrasound on adsorption of Geniposide on Resin1300 in a fixed bed were studied and compared. Amount of Geniposide adsorbed on Resin 1300 in the presence of ultrasound is lower than that in the absence of ultrasound, but the mass-transfer rate with ultrasonic irradiation is higher than that without ultrasound. Furthermore, mass transfer rate is enhanced by pulse modulation. In the conditions studied, the adsorption equilibrium constant decreases with increasing ultrasonic power, while the overall mass-transfer coefficient increases. With increasing pulse duty ratio, adsorption equilibrium constant decreases initially, reaches a minimum when pulse duty ratio is 0.5, and then increases. On the contrary, the overall mass-transfer coefficient increases initially and reaches a maximum when pulse ratio is 0.5, and then decreases. Effects of pulse period on adsorption equilibrium and mass transfer rate reached the peak at pulse period of 28.6 ms.

The free fatty acids in waste oil with high acid value were removed and transformed into fatty acid methyl esters by the extraction-reaction coupled process. The de-acidification efficiency and esterification conversion in the extraction-reaction coupled process were studied and compared with those in the stand-alone extraction process and the esterification process, respectively. Compared with cross-current batch extraction, the de-acidification efficiency of the extraction-reaction coupled process was equivalent to that of seven equilibrium stages in the conditions of the oil/methanol mass ratio of 1:1 at 60 oC. Compared with the esterification process, the esterification conversion of the coupled process was 90.3%, which is much larger than 46% in the esterification process at the reaction time of 32 minutes. Based on these findings, it is suggested that the extraction-reaction coupled process is a very effective and promising method for biodiesel production from oils having high acid value.

The TMPRSS2:E‑twenty‑six (ETS) gene fusion occurs frequently in a high proportion of patients with prostate cancer (PCa) in Western countries, and the aberrant expression of TMPRSS2: v‑ETS avian erythroblastosis virus E26 oncogene homolog (ERG), the most common form of the corresponding protein, can regulate cell migration and contribute to tumor invasion and metastasis. However, its association with other cellular events, and in particular, cell death, remain unknown. To examine the function of such fusion genes, an expression plasmid containing the TMPRSS2:ERG (T1/E5) sequence (ΔERG) from a patient sample was constructed and transiently transfected into DU145 cells, which do not express the fusion gene. It was found that the overexpression of ΔERG significantly inhibited the ability of cisplatin to induce apoptosis in DU145 cells. By contrast, VCaP cells, which do contain TMPRSS2:ERG, were sensitized to cisplatin‑induced apoptosis through siRNA inhibition of the fusion gene. To elucidate the underlying mechanism, a stable cell line expressing the ΔERG gene was constructed. Expression of ΔERG did not affect cell migration, but did protect cells from DNA damage and apoptosis induced by cisplatin. Furthermore, knockdown of ΔERG by short interfering RNA resulted in cells regaining their sensitivity to cisplatin. Finally, the gene coding for activating transcription factor 5, which is important for cell survival, may be upregulated by ΔERG. Taken together, these data point to a new function of the TMPRSS2:ERG fusion gene in regulating the apoptotic pathway.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Angiogenesis is reported to play a pivotal role in the occurrence, development and metastasis of HCC. The renin-angiotensin system (RAS) is involved in the regulation of angiogenesis. Here, based on the analysis of HCC datasets from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA), we found that there was a negative correlation between the mRNA levels of angiotensin converting enzyme 2 (ACE2) and CD34. To explore the association of RAS with the progression from fibrosis to cirrhosis to HCC, liver specimens and serum samples were collected from patients with hepatic fibrosis, cirrhosis and HCC. Relative hepatic mRNA levels of CD34 and ACE2 were determined by real-time PCR, and the serum concentrations of Angiotensin II (Ang II), Ang (1-7) and vascular endothelial growth factor (VEGF) were detected by ELISA. We found that ACE2 mRNA was gradually decreased, while CD34 mRNA was progressively increased with the increasing grade of disease severity. Concentrations of Ang II, Ang (1-7) and VEGF were higher in the sera of patients than in that of healthy volunteers. These proteins' concentrations were also progressively increased with the increasing grade of disease severity. Moreover, a positive correlation was found between VEGF and Ang II or Ang (1-7), while negative correlation was observed between mRNA levels of CD34 and ACE2. More importantly, patients with higher level of ACE2 expression had longer survival time than those with lower level of ACE2 expression. Taken together, our data suggests that the low expression of ACE2 may be a useful indicator of poor prognosis in HCC. The RAS may have a role in the progression of HCC.

A new intraoperative cisplatin administration method for patients with locally advanced gastric cancer (AGC) and without peritoneal metastasis, fibrin-sealant-delivered cisplatin chemotherapy, was reported, and its safety, pharmacokinetics, and efficacy were compared with cisplatin hyperthermic intraperitoneal perfusion chemotherapy. Forty-two AGC patients were randomly divided into 2 groups: fibrin-sealant-delivered cisplatin chemotherapy (FS) (n = 21) and cisplatin hyperthermic intraperitoneal perfusion chemotherapy (CHIC) (n = 21). Both groups received 120 mg cisplatin after complete cytoreductive surgery. At different time points, cisplatin concentrations in patients’ sera and urine samples were measured to determine time-dependent maximal concentration (Cmax) and the area under the curve (AUC). The primary and secondary end-points were overall survival (OS) and safety profiling, respectively. Occurrence of grade-3 to grade-4 liver or kidney dysfunction was less frequent in the FS group than in the CHIC group (28.6 % vs 47.6 %). Cisplatin Cmax and AUC for the serum and urine of the FS patients were significantly lower than that of the CHIC patients. Elimination half-life of cisplatin in the FS group was significantly longer than in the CHIC group (24.1 h vs 14.2 h). After a median follow-up of 40 months, 1-, 2-, and 3-years OS were 90.5 %, 71.4 %, and 61.9 % in the FS group, and 61.9 %, 47.6 %, and 42.8 % in the CHIC group, respectively. The median OS was 35.9 months in the FS group and 29.1 months in the CHIC group. Fibrin-sealant-delivered cisplatin chemotherapy was as effective and had a favorable pharmacokinetic profile with similar survival outcomes as cisplatin hyperthermic intraperitoneal perfusion chemotherapy following complete cytoreductive surgery of locally advanced GC without peritoneal metastases.

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.

For analysis of nitration modification of α oxoglutarate dehydrogenase (α-OGDH) induced by diabetes, a targeted proteomics strategy was developed through the use of Skyline. All peptides containing Y and W of the target proteins were nitrated in silico and output to produce parallel reaction monitoring (PRM) or SRM method for nitration analysis. A nitrated casein mixture was used as standard protein to assess the feasibility of this method. The results demonstrated the availability of this strategy for nitration identification, and subsequently this method was used to analyze the nitration of α-OGDH from myocardial tissue extracts of diabetic mouse. The PRM method was primarily generated by Skyline for identification of the actual nitrated peptides from all possible nitrated peptides of α-OGDH due to the complexity of α-OGDH. The PRM-based data were analyzed by SEQUEST, and transitions of the identified nitrated peptides were used to develop an SRM method for relative quantitation of nitration degree. The nitration degree of α-OGDH for diabetic mouse is higher than that for control mouse, indicating that α-OGDH of the diabetic mouse suffered from more intense oxidative damage. We believe that this approach for obtaining information regarding nitration will facilitate the study of other PTMs in complex mixtures.

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.

Nitrogen source is one of the important factors that affect the microalgae growth and lipid accumulation. We studied the effects of various nitrogen sources (i.e. NaNO3, CO(NH2)2, NH4Cl and CH3COONH4) and amount on the growth density, lipid yield, and eicosapentaenoic acid (EPA) content of Nannochloropsis oculata by single factor experimental method. The results show that N. oculata preferred NH4+ as nitrogen source rather than NO3- and CO(NH2)2. NH4+ could promote the growth and lipid accumulation of N. oculata. With the increase of nitrogen concentration, the biomass and the content of polyunsaturated fatty acid (PUFA) increased, but the content of lipid decreased. CH3COONH4 was the most suitable for growth, accumulation of lipid and EPA of N. oculata among the four investigated nitrogen sources. The optimal concentration was 5.29 mmol/L.

Extensive research focused on finding effective strategies to prevent or improve recovery from myocardial ischaemia/reperfusion (I/R) injury. Basic fibroblast growth factor (bFGF) has been shown to have therapeutic potential in some heart disorders, including ischaemic injury. In this study, we demonstrate that bFGF 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, bFGF 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 bFGF. Taken together, our results indicate that the cardioprotective role of bFGF 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.

Hollow porous micro/nanostructures with high surface area and shell permeability have attracted tremendous attention. Particularly, the synthesis and structural tailoring of diverse hollow porous materials is regarded as a crucial step toward the realization of high-performance electrode materials, which has several advantages including a large contact area with electrolyte, a superior structural stability, and a short transport path for Li(+) ions. Meanwhile, owing to the inexpensive, abundant, environmentally benign, and renewable biological resources provided by nature, great efforts have been devoted to understand and practice the biotemplating technology, which has been considered as an effective strategy to achieve morphology-controllable materials with structural specialty, complexity, and related unique properties. Herein, we are inspired by the natural microalgae with its special features (easy availability, biological activity, and carbon sources) to develop a green and facile biotemplating method to fabricate monodisperse MnO/C microspheres for lithium-ion batteries. Due to the unique hollow porous structure in which MnO nanoparticles were tightly embedded into a porous carbon matrix and form a penetrative shell, MnO/C microspheres exhibited high reversible specific capacity of 700 mAh g(-1) at 0.1 A g(-1), excellent cycling stability with 94% capacity retention, and enhanced rate performance of 230 mAh g(-1) at 3 A g(-1). This green, sustainable, and economical strategy will extend the scope of biotemplating synthesis for exploring other functional materials in various structure-dependent applications such as catalysis, gas sensing, and energy storage.

Effects of carbon sources (Na2CO3, NaHCO3 and glucose) and concentration of NaHCO3 on the growth density and lipid contents of Nannochloropsis oculata were studied. N. oculata preferred inorganic carbon to glucose, the growth density and lipid content of algae cultured with NaHCO3 were higher than that with glucose. The effects of concentration of NaHCO3 on growth density and lipid content were related to inoculation density and nitrogen level. In high nitrogen level, the concentration of NaHCO3 had little effect on the growth density, but in low nitrogen level, the growth density increased at first, and then decreased with the increase of concentration of NaHCO3. Based on the results we suggest that an optimum ratio of carbon to nitrogen was existed. Furthermore, we found the optimum ratio was changed with inoculation density. The optimum ratio of carbon to nitrogen was 3 when inoculation density was OD440 of 0.10, the optimum ratio increased to 5 with OD440 of 0.70. Concentration of NaHCO3 and ratio of carbon to nitrogen had significant effects on the lipid content and productivity. Lipid content reached the highest value when the ratio of carbon to nitrogen was 1 with experimental range of nitrogen level and inoculation density. The lipid productivity was 56.7 mg/(L.d) , and the EPA productivity was 6.5 mg/(L.d) at optimum cultivation condition with NaHCO3 as carbon source, the ratio of carbon to nitrogen at 1, the concentration of NaNO3 at 0.225 g/L, and the inoculation density with OD440 of 0.70.

The effects of trace elements on the lipid productivity and fatty acid composition ofNannochloropis oculata (N. oculata)were studied. The results showed that trace elements had a strong influence on not only the lipid productivity but also the fatty acid composition. The addition of Fe3+, Zn2+, Mn2+, Mo6+, and EDTA and the deletion of Cu2+and Co2+can increase the lipid productivity. The optimum concentrations of the trace elements in the culture medium are 6 times of Fe3+and EDTA, the same concentration of Zn2+, Mn2+, and Mo6+as the control group, but the optimum medium has no Cu2+or Co2+. Fe3+, Zn2+, Mn2+, Mo6+, and EDTA are indispensable during the EPA formation ofN. oculata. The addition of Fe3+, Zn2+, Mn2+, Mo6+, and EDTA can strongly increase the content of EPA in the lipid ofN. oculata, but the concentration of the trace elements had little influence on the level of EPA.

Bi-functional catalysts consisting of platinum on aluminosilicate MCM-41 materials with Si/Al ratios between 10 and 30 were prepared via direct mixed-gel synthesis. The catalysts were tested in the hydrocracking of bio-alkanes, produced from biodiesel hydrodeoxygenation and composed of n-hexadecane and n-octadecane, for the production of bio-jet fuel. The effects of temperature, pressure, weight hourly space velocity (WHSV), and H2/n-paraffin weight ratio on bio-alkanes conversion and product distribution were examined. The conversion was found to be dependent on the acid strength of the catalyst supports which were proportional to the Al content. However, the catalyst selectivity decreased with the increasing Al content. The optimal Si/Al ratio, temperature, pressure, WHSV, and H2/n-paraffin weight ratio were determined to be 20, 330 °C, 2 MPa, 1 h−1, and 0.20, respectively. Under these conditions, the bio-alkanes conversion and kerosene/gasoline ratio in the product reached 65.62% and 1.96, respectively.

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) were developed for the treatment of benign lesions and early superficial esophageal cancers in the gastrointestinal (GI) tract. However, esophageal strictures frequently develop in patients who undergo EMR/ESD. Therefore, we aimed to investigate the clinical value of preventive balloon dilatation (BD) for esophageal diseases following endoscopic therapy. A total of 30 patients who had received EMR or ESD were enrolled in the study. Preventive BD was carried out for 12 cases within 1 week following EMR/ESD. The remaining 18 cases were not subjected to preventive BD and were used as an historic control. The results revealed that no complications, including esophageal stenosis and dysphagia, were observed in the patients who received preventive BD. In the control group, seven cases experienced dysphagia, of which two were released without clinical treatment and the other five were released following two or three BD procedures. The results indicate that preventive BD is an effective treatment for patients with esophageal diseases following EMR and should be considered at an early stage when the mucosal injury exceeds two-thirds of the esophageal lumen.

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.