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The implementation of alternative fuels, such as biodiesel, in engines has been shown to be a feasible strategy to control greenhouse gas (GHG) emissions. The blending of biodiesel with diesel can reduce emissions of carbon monoxide (CO) and carbon dioxide and reduce soot formation. Nonetheless, biodiesel combustion comes with low thermal efficiency, elevated emissions of nitrogen oxides (NOx) and carbon deposition issues. Recently, the addition of gasoline to diesel–biodiesel blends has been proposed to compensate for the downsides of biodiesel combustion. In the current review, the viability of using this ternary fuel blend in engines is thoroughly reviewed. The review first assesses the environmental and health issues caused by conventional fuels, mitigation schemes to control GHG emissions and alternative fuels as a decarbonizing technology. The combustion and emissions characteristics of diesel–biodiesel–gasoline mixtures are discussed in detail. Finally, the status, challenges and prospects of applying the alternative fuel mixture in engines are appraised. This work has revealed that the mixing of gasoline with diesel–biodiesel blends brings about elongated ignition delay, increased heat release rate and in-cylinder pressure at high loads. Additionally, by adding gasoline, the combustion duration is shortened and soot, CO and unburned hydrocarbon emissions are suppressed, while NOx emissions are slightly increased. Combustion stability is found to be partially disrupted in the presence of gasoline whereas fuel economy (at medium and high loads) is improved by the addition of gasoline. To support the wider deployment and commercialization of this fuelling strategy in the transportation sector, favourable legislation and/or fiscal incentives are needed in countries around the world. This would encourage researchers, fuel producers and engine manufacturers alike to solve challenges such as biodiesel feedstock costs, fuel quality, fuel storage management and engine warranty issues.

In this research, the spray combustion, soot formation and exhaust emissions of diesel, biodiesel, gasoline fuels and their mixtures are analysed in a constant volume chamber. A multicomponent kinetic mechanism (CDBG) suitable for diesel-biodiesel-gasoline mixtures developed by our research group is utilised, and the associated physicochemical properties are thoroughly calculated. Adaptive mesh refinement scheme with appropriate mesh independency analysis are applied. Liquid penetration length, lift-off length, ignition delay and soot formation have been benchmarked against experimental data in the literature. A hybrid RANS-LES model, known as DES model, is used to simulate the turbulent condition. The effects of different ambient temperature/oxygen levels on the flame structure, soot formation and emissions of different ternary mixtures of D75|BD20|G5, D70|BD20|G10 and D65|BD20|G15 were analysed. D65|BD20|G15 resulted in a lower soot mass yield than that of BD100 (pure biodiesel) and D100 (pure diesel) for about 35% and 27%, respectively, at T = 900 K | O2 = 15%. Greater soot mass reductions for the tested fuels were captured by the decrease in ambient temperature from 900 K to 800 K by a factor of ∼1/3 (same ambient O2 concentration). Lower nitrogen oxides (NOx) emissions were obtained for D100 by factors of ∼1/2 at T = 900 K | O2 = 15% compared to BD100. Gasoline-added mixtures revealed lower NOx compared to BD100 (∼20%) yet still higher than D100. Lower carbon dioxide (CO2) and carbon monoxide (CO) emissions were captured for D65|BD20|G15 compared to BD100 and D100.

Louvers are an integral component of natural ventilation. This study presents a numerical analysis using\ud computational fluid dynamics (CFD) on cross ventilation in an isolated building equipped with louvers. Opening\ud configurations of (i) center-center, (ii) top-top, (iii) bottom-bottom, (iv) top-bottom and (v) bottom-top (whereby\ud the configurations are defined as ‘windward’-‘leeward’) with varying louver configurations of No-Louver (NL),\ud 0◦, 15◦, 30◦ and 45◦ are studied. Atmospheric Boundary Layer (ABL) condition is applied at the inlet of the flow\ud domain and Renormalization Group (RNG) k-ε turbulence model with enhanced wall function (EWT) is\ud employed for the numerical simulations. Grid sensitivity analysis is performed using Grid Convergence Index\ud (GCI) whilst model validation is performed using Factor of two of observation (FAC2) analysis. The highest\ud dimensionless flow rate (DFR) is achieved by configuration top-top without louvers at 0.719. The highest air\ud exchange efficiency (AEE) is obtained by louver angle of 15◦ for center-center configuration at 53.4%. The lowest\ud AEE obtained is obtained at louver angle of 0◦ for top-top configuration at 20%, indicating short-circuiting of air.\ud For configuration bottom-bottom with louver angle of 30◦, high AEE is obtained but at the cost of reduced DFR.\ud The optimal balance between AEE and DFR can be obtained by factor-optimization (α) as presented in this paper.\ud The study concludes that opening position alongside louver angle plays an integral role on the internal airflow,\ud pressure coefficient, DFR and AEE in natural cross ventilation.

Hepatic sinusoidal obstruction syndrome (HSOS) is a serious side effect of oxaliplatin (OXA) treatment. The present study aimed to establish a reproducible mouse model of OXA‑induced HSOS and to preliminarily explore the underlying molecular mechanisms using mRNA microarray analysis. A total of 45 C57BL/6 male mice were randomly divided into five groups: Control, 5 mg/kg OXA, 10 mg/kg OXA, 15 mg/kg OXA and 20 mg/kg OXA. The mice were respectively injected intraperitoneally with 5% glucose solution, or 5, 10, 15 or 20 mg/kg OXA solution once a week for 6 consecutive weeks. The body weight of the mice was recorded every day. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. Hematoxylin and eosin staining, Sirius red staining and scanning electron microscopy were used to identify pathological changes. mRNA microarray was used to analyze changes in the gene expression profiles mainly from the functional aspects of Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. The oxidation mechanism was verified by measuring oxidative stress‑related markers and reactive oxygen species with dihydroethidium probe technology, according to the microarray results. Among all of the OXA groups, 10 mg/kg OXA resulted in an acceptable survival rate of 78%. The mice showed obvious splenomegaly, increases in serum levels of ALT and AST, aggravation of liver pathological injuries and hepatic sinusoidal injuries. The microarray results suggested that mRNA expression changes after OXA treatment were associated with 'oxidative stress', 'coagulation function', 'steroid anabolism' and 'pro‑inflammatory responses'. The results confirmed that OXA aggravated oxidative damage in the livers of the mice. The present study successfully established a mouse model of OXA‑induced HSOS and preliminarily analyzed the underlying molecular mechanisms involved, thus laying a foundation for a subsequent in‑depth study.

In this paper, the formulation of a reduced chemical kinetic mechanism for iso-pentanol fuel is presented. First, the main reaction pathway and pertinent key species for isopentanol oxidation were identified. Then, the detailed chemical kinetic mechanism for iso-pentanol was reduced using reduction techniques which included directed relation graph, isomer lumping and temperature sensitivity analysis, where a reduced mechanism of 92 species and 444 reactions was obtained. The reduced mechanism for iso-pentanol was validated against experimental data as well as detailed mechanism predictions under zero-dimensional shock tube autoignition and jet-stirred reactor (JSR) conditions, at initial temperatures from 650 K to 1350 K, initial pressures from10.1 bar to 60 bar and equivalence ratios between 0.5 and 2.Under the shock tube auto-ignition conditions, more than85% of the experimental measurements and detailed mechanism predictions for the ignition delay (ID) of iso-pentanolwere replicated by the reduced mechanism. Similarly, species profiles under the JSR conditions which were related to the formation of oxidation, aldehyde and emissions for isopentanol were also reproduced. Furthermore, the rate of production analysis revealed that the elementary reactions associated to the oxidation of iso-pentanol in the detailed mechanism were successfully retained in the reduced mechanism. Meanwhile, the computational runtime was saved by three times when the reduced mechanism was implemented to model the simulations. These results therefore indicate that the reduced mechanism developed for iso-pentanol is sufficient and reasonable.

In this research, a multi-input multi-output artificial neural network (MIMO-ANN) is developed, in which 14 features associated with the engine performance and stability, emissions, combustion and ignition characteristics of diesel-biodiesel-gasoline mixtures are meant to be modelled by a diverse combination of engine/combustion parameters. The selected targets comprise brake specific fuel consumption (BSFC), brake thermal efficiency (BTE), combustion efficiency, coefficient of variance (COV), NOx, CO2, CO and HC emissions, exhaust temperature (Texh), in-cylinder pressure (Pcyl), maximum pressure rise rate (MPRR), heat release rate (HRR), combustion duration (CD) and ignition delay (ID). The inputs variables entail the load, speed, compression ratio, gasoline, biodiesel and diesel ratios, crank angle (CA), injection temperature (Tinj), injection pressure (Pinj), brake mean effective pressure (BMEP) and start of injection (SOI). Sensitivity analysis and outlier detection are applied in order to eliminate less-effective inputs/data points. The prepared data sets are then used to train and test the ANN model, in conjunction with benchmarking the model outcomes using coefficient of determination (R2), average absolute relative deviation (AARD) and relative mean squared errors (RMSE). The R2 ranged within 0.9804–0.9998, which is close to unity, proving that the proposed network is accurately capable of predicting the intended combustion characteristics.

In this study, the ignition characteristics of ethanol blended with hydro-processed renewable diesel (HRD) in a constant volume combustion chamber were conducted in both experiments and zero-dimensional (0-D) chemical kinetic simulations. The experimental results revealed that ignition delay (ID) increased with increasing ethanol concentration. The emissions of carbon dioxide (CO2), carbon monoxide (CO), nitrogen oxides (NOx), and hydrocarbon (HC) under lean and stoichiometric conditions were studied at a chamber pressure (Pchamb) of 7 bar. It was found that CO2 emissions reduced with increasing ethanol concentration. However, opposite trend was observed for NOx emissions. Since ethanol has a lower heating value than HRD fuel, the combustion temperature was reduced with the use of the HRD-ethanol blend, which subsequently resulted in lower NOx formation. The addition of ethanol also increased the oxygen concentration which aided in promoting further oxidization of CO to form CO2, thereby reducing the amount of CO produced. Besides, the effect of the addition of ethanol in HRD on HC emission was also observed whereby increasing its ratio increased the oxygen concentration in fuel which had the advantage of reducing HC emission. A kinetic model of 144 species and 600 reactions for the ethanol blended with HRD was also formulated. The kinetic model reasonably reproduced the measured ID periods at initial pressures of 10–20 bar, temperatures of 600–818 K and equivalence ratios of 0.13–0.354, despite quantitative disagreement with the experiment at the lower temperatures. Additionally, the measured trend where the ID periods elongated with respect to the increase in the ethanol concentration was replicated by the kinetic model.

In this study, a numerical investigation on the effects of ozone addition on the laminar premixed flame development and emissions formation of carbon monoxide (CO) and nitrogen oxides (NOx) for methane and propane in a co-flow burner is presented. Simulations for the reacting mixtures with the addition of ozone concentrations of 3810 ppm and 6000 ppm were performed at atmospheric pressure, ambient temperature of 298 K and equivalence ratios (φ) of 0.8, 1.0 and 1.3. Based on the simulation results, ozone improved the flame development, where the flame temperatures for methane/propane were raised by 42 K (maximum difference). Besides, the formaldehyde (CH2O) and hydroxyl (OH) mass fractions were also increased and subsequently elongated the stand-off distances for methane/propane by 12%. The laminar burning velocities for methane/propane were accelerated by 8.7%, which were contributed by the higher rates of fuel oxidation due to the increased ozone concentration. Although the CO and NOx mass fractions for the ozone enhanced methane/propane flames were deviated by a maximum difference of 29%, the effect of ozone on these emissions were found varied according to the fuels and φ values.

Expression of Bcl-2 and Akt-1 has been associated with human cancer. G3139 and RX-0201, targeting Bcl-2 and Akt-1, respectively, are antisense oligonucleotides (ASOs) that have shown limited efficacy in clinical trials. Herein, we report a combination of newly designed ASOs based on these agents and was delivered by tumor cell-targeting lipid nanoparticles (LNPs). A "Gapmer" design strategy was applied to these ASOs with the addition of 2'-O-methyl modifications on the nucleotides at 5' and 3' ends. A dual-channel syringe pump-based system was developed for the synthesis of the LNPs. ASO-LNPs composed of DODMA, egg PC, cholesterol, T7-PEG-DSPE, and PEG-DMG at a molar ratio of 35:39.5:20:0.5:5 and carrying either individual ASOs or co-loaded ASO combinations (Co-ASOs) were synthesized and evaluated in both KB and A549 cancer cells and in an A549 murine xenograft model to determine their antitumor effects and biological activities. The ASO-LNPs exhibited excellent colloidal stability and high ASO encapsulation efficiency with relatively small mean particle sizes and moderately positive zeta potentials. Transferrin receptor-targeting T7-conjugated LNPs showed enhanced cellular uptake compared to nontargeted LNPs. In addition, both T7-conjugated Co-ASOs-LNPs and non-T7-conjugated Co-ASOs-LNPs at a molar ratio of (G3139-GAP to RX-0201-GAP at 1:2) showed efficient downregulation of both Bcl-2 and Akt-1 in both A549 and KB cells. Furthermore, T7-conjugated Co-ASOs-LNPs (Co-ASOs-LNPs) produced superior antitumor activity, prolonged the overall survival time, and demonstrated tumor targeting activity in an A549 xenograft model.

This work presents a numerical analysis of spray combustion and associated emissions formation for methyl esters of soybean (SME) and coconut (CME) in a constant volume bomb and a light-duty diesel...

RX-0201 is an antisense oligonucleotide (ASO) against Akt1 currently in clinical trial for metastatic renal cancer.To improve the delivery of RX-0201 using folate receptor-targeted lipid-albumin nanoparticles (F-LAN).F-LAN were synthesized with the composition of DOTAP/soyPC/TPGS/folate-PEG-DSPE (25:70:4:1 m/m), a cationic human serum albumin-pentaethylenehexamine (HSA-PEHA) conjugate and RX-0201. The nanoparticles were evaluated in KB human carcinoma cells in vitro and in a KB murine xenograft tumour model in vivo for pharmacokinetics and antitumor activities.The F-LAN-RX-0201 had a mean particle size of 108.6 ± 5.8 nm, zeta potential of 10.5 ± 3.2 mV and ASO loading efficiency of 71.5 ± 4.5%. In KB cells, uptake and Akt1 inhibition by F-LAN-RX-0201 were greater than those of non-targeted LAN-RX-0201 and could be partially blocked by excess free folate. F-LAN-RX-0201 inhibited cell growth with an ICF-LAN-RX-0201 showed promise as a therapeutic agent for tumours with elevated folate-receptor expression.

We performed molecular dynamics simulations of the high voltage pulse explosion of single aluminum wires with the energy ratio of 0.6 in vacuum and studied the role of wire radial dimension. Simulation results show that large-diameter wires having a large material depth and a small specific surface can maintain a higher deposition energy density and effectively reduce the influence of the radial difference in thermodynamic parameters, leading to higher explosion velocity and a lower vaporization rate in the large-diameter wire. The most significant effect is that the larger diameter wire has a longer explosion development time. In addition, the propagation and reflection of the rarefaction waves in the wire result in two explosion regimes: the spinodal decomposition propagating inward from the surface and the cavitation boiling from the center to the surface. Increasing the diameter will increase the domination range of the spinodal decomposition mechanism.

In this study, the performance of a gas-fired radiant-tube which was fuelled with syngas and air mixtures was investigated numerically using ANSYS Fluent version 17.2. The burner was operated in a non-premixed mode with swirled air. The exhaust emissions of nitrogen oxides (NOx) and carbon monoxide (CO) as well as the temperature distributions along the radiant tube were analysed for three different syngas fuels which were composed of hydrogen (H2) and CO, with ratios (by vol.) of 75:25, 50:50, and 25:75. The simulations were conducted at equivalence ratio values of 0.82, 0.7 and 0.5, while the air flow Reynolds numbers were set to 5400, 6320 and 8850. Based on the simulation results under all the tested conditions, it was found that the 75H2:25CO syngas fuel performed better, where the non-uniformity parameter calculated for this fuel was 35% lower than that of the 25H2:75CO. In terms of CO emissions, 75H2:25CO had the lowest value among the tested fuels, where the maximum difference as compared to that of the 25H2:75CO was up to 93%. Meanwhile, the NOx emissions predicted for 75H2:25CO were approximately 67% lower than those of the 25H2:75CO.

To date, in the struggle against diseases and the development of TCM, what we lack is wisdom rather than knowledge. Studies on pharmacology of traditional Chinese medicine are facing critical challenges on how to select the proper parameters or targets to represent the pharmacological evaluation system. With seven steps of optimized modules established by ourselves, we can re-evaluate TCM in a panorama view with a proper pharmacological evaluation system. In this article, with the treatment of TCM as 'interaction of system to system', a novel and generally applicable approach called fuzzy target contribution recognition was established and agents from Astragali Radix-Fructus Corni in resisting diabetic nephropathy were successfully discovered for the first time. CG6, a promising agent from this herb-pair on the treatment of diabetic nephropathy, was finally acquired and its possible molecular mechanism was explored through a nuclear factor erythroid 2-Like 2 (NFE2L2) activation-dependent pathway.

Lipid-albumin nanoparticles (LAN) were synthesized for delivery of RX-0047, an antisense oligonucleotide (ASO) against the hypoxia inducible factor-1 alpha (HIF-1α) to solid tumor. These lipid nanoparticles (LNs) incorporated a human serum albumin-pentaethylenehexamine (HSA-PEHA) conjugate, which is cationic and can form electrostatic complexes with negatively charged oligonucleotides. The delivery efficiency of LAN-RX-0047 was investigated in KB cells and a KB murine xenograft model. When KB cells were treated with LAN-RX-0047, significant HIF-1α downregulation and enhanced cellular uptake were observed compared to LN-RX-0047. LN-RX-0047 and LAN-RX-0047 showed similar cytotoxicity against KB cells with IC50 values of 19.3 ± 3.8 and 20.1 ± 4.2 μM, respectively. LAN-RX-0047 was shown to be taken up by the cells via the macropinocytosis and caveolae-mediated endocytosis pathways while LN-RX-0047 was taken up by cells via caveolae-mediated endocytosis. In the KB xenograft tumor model, LAN-RX-0047 exhibited tumor suppressive activity and significantly reduced intratumoral HIF-1α expression compared to LN-RX-0047. Furthermore, LAN-RX-0047 greatly increased survival time of mice bearing KB-1 xenograft tumors at doses of either 3 mg/kg or 16 mg/kg. These results indicated that LAN-RX-0047 is a highly effective vehicle for therapeutic delivery of antisense agents to tumor.

MicroRNA-21 (miR-21) is an oncomiR that is frequently upregulated in human cancers. AntimiR-21 (AM-21) is an oligonucleotide complementary to miR-21 that is designed to inhibit its gene silencing activities. To facilitate efficient delivery of AM-21, a novel lipid nanoparticle formulation called QTsome, based on a combination of quaternary amine and tertiary amine cationic lipids, with a distinctive pH-responsive profile, was developed. QTsome/AM-21 comprising DODMA/DOTAP/DOPC/CHOL/mPEG-DPPE and AM-21 oligonucleotide exhibited a mean particle diameter of below 150 nm, moderate zeta potential (+13.2 mV), excellent colloidal stability, and high drug loading efficiency (above 80%). In vitro study showed QTsome/AM-21 induced upregulation of miR-21 targets, including PTEN and DDAH1, in A549 cells while increasing their sensitivity toward paclitaxel (PTX). Finally, tumor regression, prolonged survival, and miR-21 target upregulation were demonstrated in an A549 xenograft mouse model. These data suggest that QTsome/AM-21 warrants further evaluation as an anticancer agent.

This work numerically examines the quasi-steady spray combustion and soot development for soybean methyl ester (SME) and SME-ethanol blends (S90E10, S70E30). A validated reduced ethanol mechanism (37 species and 149 reactions) was formulated using a temperature sensitivity analysis under auto-ignition and jet-stirred reactor conditions. At initial pressures between 10.0 bar and 60.0 bar, initial temperatures between 750 K and 1350 K and equivalence ratios between 0.5 and 2.0, the ignition delays and key species profiles (C2H5OH, CO2, O2) of the reduced mechanism deviated by 0.5 order and 40%, respectively as compared to the experimental measurements. Subsequently, the reduced ethanol mechanism was combined with a reduced biodiesel mechanism to form a surrogate mechanism (102 species and 446 reactions) for biodiesel-ethanol blends and integrated into OpenFOAM for spray combustion modelling. Under reacting spray conditions at a constant ambient density of 22.8 kg/m3 and ambient temperatures of 900 K and 1000 K, the spray penetrations for SME-ethanol blends were shortened by 35.5% (maximum difference). Smaller flame areas with 60 K higher local flame temperature were obtained. Due to a 20% decrease in acetylene mass fractions and soot formation rates, the peak soot volume fractions for SME-ethanol blends were 19.6% lower.

In this reported work, a generic reduced biodiesel chemical kinetic mechanism, with components of methyl decanoate (C 11 H 22 O 2, MD), methyl-9-decenoate (C 11 H 20 O 2 , MD9D) and n-heptane (C 7 H 16 ) was built to represent the methyl esters of coconut, palm, rapeseed and soybean. The reduced biodiesel mechanism with 92 species and 360 elementary reactions was developed using reduction techniques of directed relation graph (DRG), isomer lumping and temperature sensitivity analysis. The reduced biodiesel mechanism was then validated under various shock tube conditions against experimental measurements and detailed mechanism predictions, for each zero-dimensional (0D) auto-ignition and extinction process using CHEMKIN-PRO. Maximum percentage errors of less than 40.0% were recorded when the predicted ignition delay (ID) periods for coconut, palm, rapeseed and soybean methyl esters were compared to those of the respective detailed mechanisms. Predicted key species profiles in extinction process for each biodiesel fuel such as hydroxyl (OH), hydroperoxyl (HO 2 ), carbon dioxide (CO 2 ), ethylene (C 2 H 4 ) were also found to be in reasonable agreement to those produced from the respective detailed mechanism, with a maximum deviation of 1 order in the mole fraction values. Meanwhile, satisfactory agreement was achieved when the predictions of reduced mechanism were compared against the measured ID periods of MD auto-ignition event in shock tube conditions and key species profiles of RME oxidation in jet stirred reactor (JSR). In the next stage of extended validation, the reduced biodiesel mechanism was implemented for two-dimensional (2D) computational fluid dynamics (CFD) spray combustion modelling, with initial temperatures of 900 K and 1000 K at an ambient density of 22.8 kg m −3 . Based on the simulation results, liquid penetration for soybean biodiesel was accurately predicted by the reduced mechanism as compared to the experimental data. Good agreements in the ID and lift-off length predictions were also achieved, where the ID was only advanced by 2.8% while the lift-off length was over-predicted by 17.3% from the experimental measurements when the initial temperature was 900 K. Meanwhile, the predicted ID and lift-off length at the initial temperature of 1000 K were both over-estimated by 29.8% and 43.4%, respectively. Thus, the reduced biodiesel mechanism formulated here is essentially accurate in predicting the in-cylinder ignition, combustion and extinction phenomena.

Jinlong Zhao,1 Menghui Zhao,1 Changhui Yu,1 Xueyan Zhang,1 Jiaxin Liu,1 Xinwei Cheng,2 Robert J Lee,1,2 Fengying Sun,1 Lesheng Teng,1 Youxin Li1 1School of Life Sciences, Jilin University, Changchun, China; 2College of Pharmacy, Ohio State University, Columbus, OH, USA Abstract: Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive cartilage and bone destruction. Activated macrophages that overexpress folic acid (FA) receptors play an important role in RA, due to their abundance in inflamed synovial membrane and joints. In an effort to deliver drugs to the inflamed tissues, multifunctional FA receptor-targeting and pH-responsive nanocarriers were developed. They were composed of lipids, polyethylene glycol (PEG)–poly(lactic-co-glycolic acid) (PLGA) forming a hydrophilic shell, FA around the hydrophilic shell as a targeting ligand, and poly(cyclohexane-1,4-diylacetone dimethylene ketal) (PCADK) and PLGA as a hydrophobic core. PCADK also acts as a pH-responsive material. Methotrexate (Mtx) was encapsulated in the nanoparticles, which exhibited pH-responsive release in vitro. Cellular uptake and cytotoxicity experiments revealed that FA-PEG-PLGA/PCADK–lipid nanoparticles loaded with Mtx (FA-PPLNPs) exhibited superior cellular uptake and higher cytotoxicity to activated macrophages than PPLNPs/Mtx. The therapeutic effect of FA-PPLNPs/Mtx in RA was confirmed in an adjuvant-induced arthritis rat model. These results suggest that the multifunctional folate receptor-targeting and pH-responsive nanocarriers are promising for the treatment of RA. Keywords: rheumatoid arthritis, methotrexate, nanoparticles, folate, pH-responsive, PCADK&nbsp

The application of nanomedicines has proved to be effective for the therapy of various types of cancer compared to conventional treatments such as chemotherapy and radiation therapy. The nanomedicines can treat various cancers with the precise target without affecting the normal cells. In addition, by utilizing of enhanced permeability and retention (EPR) effect, nanomedicines can selectively targeting disease site and yield very promising therapeutic results for cancer treatment. Among all available nanomedicines, organic materials such as polymers are widely used in recent decades as biomaterials for their favorable properties like excellent biocompatibility, easy design and preparation, several types of structures and interesting biomimetic character, which warrants the further evaluations on these kinds of innovative material. Inorganic nanoparticles such nanogold also demonstrated the ability to target cancer and can be employed as both therapeutic and imaging agents. This mini-review will give a brief discussion of using inorganic and organic nanoparticles for the treatment of cancer.

Traditional Chinese medicine (TCM) preparations are widely used for healthcare and clinical practice. So far, the methods commonly used for quality evaluation of TCM preparations mainly focused on chemical ingredients. The biological ingredient analysis of TCM preparations is also important because TCM preparations usually contain both plant and animal ingredients, which often include some mis-identified herbal materials, adulterants or even some biological contaminants. For biological ingredient analysis, the efficiency of DNA extraction is an important factor which might affect the accuracy and reliability of identification. The component complexity in TCM preparations is high, and DNA might be destroyed or degraded in different degrees after a series of processing procedures. Therefore, it is necessary to establish an effective protocol for DNA extraction from TCM preparations. In this study, we chose a classical TCM preparation, Liuwei Dihuang Wan (LDW), as an example to develop a TCM-specific DNA extraction method. An optimized cetyl trimethyl ammonium bromide (CTAB) method (TCM-CTAB) and three commonly-used extraction kits were tested for extraction of DNA from LDW samples. Experimental results indicated that DNA with the highest purity and concentration was obtained by using TCM-CTAB. To further evaluate the different extraction methods, amplification of the second internal transcribed spacer (ITS2) and the chloroplast genome trnL intron was carried out. The results have shown that PCR amplification was successful only with template of DNA extracted by using TCM-CTAB. Moreover, we performed high-throughput 454 sequencing using DNA extracted by TCM-CTAB. Data analysis showed that 3–4 out of 6 prescribed species were detected from LDW samples, while up to 5 contaminating species were detected, suggesting TCM-CTAB method could facilitate follow-up DNA-based examination of TCM preparations.

In an effort to advance the knowledge and understanding of biodiesel combustion characteristics in compression ignition engines, computational fluid dynamics (CFD) modeling has been utilized to study the in-cylinder physical and chemical events. The development of combustion kinetics and thermophysical properties of biodiesel in CFD modeling is crucial, since both of these govern the in-cylinder combustion and emission formation processes. As such, this review reports on the advances attained within three key aspects of CFD modeling of in-cylinder biodiesel combustion. The key aspects are surrogate chemical kinetic mechanisms, mechanism reduction methods, and biodiesel thermophysical properties models. Because of the complex fuel compositions, combustion modeling of biodiesel fuel largely depends on the surrogate chemical kinetic mechanisms. Recent developments in biodiesel chemical kinetic mechanisms have shown a progression from small detailed mechanisms toward large detailed mechanisms. The main challe...

Bcl-2 is an anti-apoptotic gene that is frequently overexpressed in human cancers. G3139 is an antisense oligonucleotide against bcl-2 that has shown limited efficacy in clinical trials. Here, we report the synthesis of a new antisense oligonucleotide containing additional chemical modifications and its delivery using nanoparticles. An oligonucleotide G3139-GAP was synthesized, which has 2’-O-methyl nucleotides at the 5’ and 3’ ends based on a “gapmer” design. Furthermore, G3139-GAP was incorporated into lipid nanoparticles (LNPs) composed of DOTAP/egg PC/cholesterol/Tween 80. The LNP-loaded G3139-GAP was evaluated in A549 lung cancer cells both in vitro and in a murine xenograft model for biological activity and therapeutic efficacy. The LNPs showed excellent colloidal and serum stability, and high encapsulation efficiency for G3139-GAP. They have a mean particle diameter and zeta potential of 134 nm and 9.59 mV, respectively. G3139-GAP-LNPs efficiently downregulated bcl-2 expression in A549 cells, as shown by 40% and 83% reduction in mRNA and protein levels, respectively. Furthermore, G3139-GAP-LNPs were shown to inhibit tumor growth, prolong survival, and downregulate tumor bcl-2 expression in an A549 murine xenograft tumor model. These data indicate that G3139-GAP-LNPs have excellent anti-tumor efficacy and warrant further evaluation.

The approach to investigate traditional Chinese medicine (TCM) is still in its infancy and has been facing enormous challenge. In this paper, a generally applicable strategy was developed for investigation on TCM systematically with an introduced interesting idea about a novel research system which called subchemome. A representative herb-pair, Astragali Radix-Fructus Corni, was successfully employed to expound this novel strategy. Firstly, subchemomes were prepared individually by applying the suitable column chromatography, each of them was detected by UV spectrophotometer or HPLC-DAD detector. The components in each part were then identified based on the mass spectrometric fragmentation patterns and tandem mass spectrometric data by using UHPLC-Q-TOF-MS. Using renal mesangial cell (RMC) viability assay as the evaluation of the pharmacological activity of each group, we developed the new mini herbal formulae aimed at diabetic nephropathy and identified fifteen marker components between the group of new mini herbal formulae and other groups from the angle of the constituent, and then explored the effects of new mini herbal formulae from another angle of the molecular mechanism. Overall, the presently developed strategy should be beneficial and widely used in the investigation on TCM from a new perspective.

This reported work investigates the sensitivities of spray and soot developments to the change of thermo-physical properties for coconut and soybean methyl esters, using two-dimensional computational fluid dynamics fuel spray modelling. The choice of test fuels made was due to their contrasting saturation-unsaturation compositions. The sensitivity analyses for non-reacting and reacting sprays were carried out against a total of 12 thermo-physical properties, at an ambient temperature of 900 K and density of 22.8 kg/m 3 . For the sensitivity analyses, all the thermo-physical properties were set as the baseline case and each property was individually replaced by that of diesel. The significance of individual thermo-physical property was determined based on the deviations found in predictions such as liquid penetration, ignition delay period and peak soot concentration when compared to those of baseline case. Among all the properties, latent heat of vaporisation produced the greatest effect on the spray and soot developments under the tested conditions, as evidenced by a longer liquid penetration of 35.0% and a reduced peak soot concentration of 22.8%. Besides, coupled effects among the thermo-physical properties were also determined. Meanwhile, the effects of thermo-physical properties were found to vary with the addition of unsaturation levels and chemical kinetics in the simulation.

Although Traditional Chinese Medicine (TCM) preparations have long history with successful applications, the scientific and systematic quality assessment of TCM preparations mainly focuses on chemical constituents and is far from comprehensive. There are currently only few primitive studies on assessment of biological ingredients in TCM preparations. Here, we have proposed a method, M-TCM, for biological assessment of the quality of TCM preparations based on high-throughput sequencing and metagenomic analysis. We have tested this method on Liuwei Dihuang Wan (LDW), a TCM whose ingredients have been well-defined. Our results have shown that firstly, this method could determine the biological ingredients of LDW preparations. Secondly, the quality and stability of LDW varies significantly among different manufacturers. Thirdly, the overall quality of LDW samples is significantly affected by their biological contaminations. This novel strategy has the potential to achieve comprehensive ingredient profiling of TCM preparations.