Regulation mechanism of endoplasmic reticulum stress on metabolic enzymes in liver diseases.

The endoplasmic reticulum (ER) plays a pivotal role in protein folding and secretion, Ca2+ storage, and lipid synthesis in eukaryotic cells. When the burden of protein synthesis and folding required to be handled exceeds the processing capacity of the ER, the accumulation of misfolded/unfolded proteins triggers ER stress. In response to short-term ER stress, the unfolded protein response (UPR) is activated to allow cells to survive. When ER stress is severe and sustained, it typically provokes cell death through multiple approaches. It is well documented that ER stress and metabolic deregulation are functionally intertwined, both are considered contributing factors to the pathogenesis of liver diseases, including non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), ischemia/reperfusion (I/R) injury, viral hepatitis, liver fibrosis, and hepatocellular carcinoma (HCC). Hepatocytes are rich in smooth and rough ER, which harbor metabolic enzymes that are capable of sensing alterations in various nutritional status and external stimuli. Extensive research has focused on the molecular mechanism linking ER stress with metabolic enzymes. The purpose of this review is to summarize the current knowledge regarding the effects of ER stress on metabolic enzymes in various liver diseases and to provide potential therapeutic strategies for chronic liver diseases via targeting UPR.

Glutathione Modified silicon-doped Carbon Quantum dots as a Sensitive Fluorescent Probe for ClO- Detection.

A selective and sensitive fluorescence method for hypochlorite (ClO-) was designed using glutathione (GSH) modified silicon-doped carbon quantum dots (GSH@Si-CDs). Then a dual emission ratio fluorescence probe (RF-probe) was obtained based on carbodiimide-activated coupling reaction between GSH and Si-CDs. i.e., when the excitation wavelength was kept at 360 nm, the GSH@Si-CDs exhibited strong blue and weak yellow fluorescence at 430 and 580 nm. Meanwhile, the fluorescence of GSH@Si-CDs could be selectively quenched at 430 nm and enhanced at 580 nm in the presence of ClO-, and corresponding limit of detection (LOD) and linear range were measured to be 0.35 µM and 1.0-33.3 µM. The sensing mechanism of the system was also investigated in detail. Moreover, the RF-probe with good accuracy was successfully employed to monitor ClO- in real samples with satisfactory results compared to the standard iodometric method.

A Ratio Fluorescence Method Based on Dual Emissive Copper Nanoclusters for the Detection of Vanillin.

In this study, a novel double-emission fluorescence probe at 340 and 400 nm was synthesized by one-pot method using phenylalanine (Phe) and ascorbic acid (AA) as stabilizing and reducing agents. It was found that the fluorescence intensity of the probe at 400 nm could be controlled by controlling the temperature within a certain range, and the ratio of double-emission fluorescence probe could be further regulated. Under the optimal conditions, the fluorescence intensity at 340 nm decreased significantly, while it only showed a slight decrease at 400 nm, which constituted the ratio fluorescence probe. The synthesized fluorescence probe showed good linearity in the range of 0.2-32 µM, and its detection limit was 63.4 nM. Moreover, the method was successfully employed to determine VA in vanilla drink and perfumes, and corresponding results were consistent with those of HPLC.

Discovery of a potent and selective CBP bromodomain inhibitor (Y08262) for treating acute myeloid leukemia.

The bromodomain of CREB (cyclic-AMP response element binding protein) binding protein (CBP) is an epigenetic "reader" and plays a key role in transcriptional regulation. CBP bromodomain is considered to be a promising therapeutic target for acute myeloid leukemia (AML). Herein, we report the discovery of a series of 1-(indolizin-3-yl)ethan-1-one derivatives as potent, and selective CBP bromodomain inhibitors focused on improving cellular potency. One of the most promising compounds, 7e (Y08262), inhibits the CBP bromodomain at the nanomolar level (IC50 = 73.1 nM) with remarkable selectivity. In addition, the new inhibitor also displays potent inhibitory activities in AML cell lines. Collectively, this study provides a new lead compound for further validation of CBP bromodomain as a molecular target for AML drug development.

Discovery and pharmacological characterization of 1,2,3,4-tetrahydroquinoline derivatives as RORγ inverse agonists against prostate cancer.

The retinoic acid receptor-related orphan receptor γ (RORγ) is regarded as an attractive therapeutic target for the treatment of prostate cancer. Herein, we report the identification, optimization, and evaluation of 1,2,3,4-tetrahydroquinoline derivatives as novel RORγ inverse agonists, starting from high throughput screening using a thermal stability shift assay (TSA). The representative compounds 13e (designated as XY039) and 14a (designated as XY077) effectively inhibited the RORγ transcriptional activity and exhibited excellent selectivity against other nuclear receptor subtypes. The structural basis for their inhibitory potency was elucidated through the crystallographic study of RORγ LBD complex with 13e. Both 13e and 14a demonstrated reasonable antiproliferative activity, potently inhibited colony formation and the expression of AR, AR regulated genes, and other oncogene in AR positive prostate cancer cell lines. Moreover, 13e and 14a effectively suppressed tumor growth in a 22Rv1 xenograft tumor model in mice. This work provides new and valuable lead compounds for further development of drugs against prostate cancer.

Optimization of the synthesis of BET BD2 selective inhibitor XY153.

XY153 is a promising BET BD2 inhibitor with an IC50 value of 0.79 nM against BRD4 BD2. It shows 354-fold selectivity over BRD4-BD1 and 6-fold selectivity over other BET BD2 domains. However, the reported synthesis route of XY153 and its derivatives are extremely poor-yielding. After the synthesis of three key fragments, XY153 can only be obtained with a yield of 1.3 % in the original four-step reaction. In this study, we reported a three-step alternative route in the synthesis process of XY153. The reaction conditions for this route were thoroughly investigated and optimized, resulting in a significantly improved yield of 61.5 %. This efficient synthesis route establishes a robust chemical foundation for the rapid synthesis of XY153 derivatives as BET BD2 inhibitors in the near future.

TGF-ß Signaling Activation Confers Anlotinib Resistance in Gastric Cancer.

BACKGROUND: Gastric cancer (GC) has always been a great threat to human health due to its aggressiveness and lethality. Anlotinib, a novel multi-target tyrosine kinase inhibitor (TKI), has been certified its anti-tumor effects on various tumors. Nonetheless, there are few studies on applying anlotinib as a treatment for GC. The underlying mechanism of acquired resistance during anlotinib administration remains unclear. METHODS: We investigated the toxicologic effects of anlotinib on GC cells through CCK8, colony-forming, and flow cytometry assays in vitro and xenograft models in vivo. Anlotinib-resistant GC cells, AGS-R and MGC803-R, were generated and characterized by cell proliferation and apoptosis assays. The signaling pathways involved in anlotinib resistance were probed using Cignal™ Finder 10-Pathway Reporter Array. Western blot and dual-luciferase reporter assays were performed to confirm the relationships. The TGF-ß inhibitor LY364947 was introduced to demonstrate the importance of TGF-ß signaling in anlotinib resistance via a series of functional assays. RESULTS: Anlotinib suppressed cell growth and induced apoptosis in vitro and inhibited tumorigenesis and metastasis in vivo, while its anti-tumor effects were impaired in anlotinib-resistant cells. The results of dual-luciferase reporter assays and western blot indicated TGF-ß signaling was activated in anlotinib-resistant GC cells. LY364947 combined with Anlotinib exerted a better antineoplastic effect than monotherapy and considerably reversed the anlotinib resistance in GC. CONCLUSIONS: Our findings suggested that TGF-ß signaling may take a significant part in anlotinib resistance in GC. The suppression of TGF-ß signaling may be a possible and promising approach for the GC oncotherapy when combined with anlotinib.

Silicon Doped Carbon Dots as an New Ratiometric Fluorescence Probe for Proanthocyanidins Assay Based on the Redox Reaction Between Cr(VI) and Proanthocyanidins.

In the study, silicon doped carbon quantum dots (Si-CQDs) was prepared by one-pot hydrothermal method with (3-aminopropyl) triethoxysilane (APTES) and o-phenylenediamine (OPD) as raw materials. Then a new ratiometric fluorescent probe (RF-probe) was successfully established for sensitively and selectively monitoring proanthocyanidins (PAs) with a linear range of 10-500 nM and limit of detection (LOD) of 5.6 nM. that is, the fluorescence (FL) intensity of Si-CQDs at 570 nm was used as the built-in reference, while dopamine (DA) reacting with 4-hexylresorcinol (4-HR) could produce a new fluorescent substance (named as azamonardine, AZMON), and its FL intensity at 480 nm was reduced because Cr(VI) could oxidize DA to generate quinone without fluorescence. In the presence of PAs, Cr(VI) was reduced to Cr(III), which caused that the amount of DA reacting with 4-HR was increased, thus the FL intensity of AZMON was recovered. Furthermore, the RF-probe was successfully used for the determination of PAs in black goji berry from two different areas and PAs capsule with satisfactory results compared to the standard HPLC method.

Sensitive Detections of Sodium Dichloroisocyanurate and Rosmarinic Acid by Polyvinylpyrrolidone Coated Copper Nanoclusters.

In this article, the water-soluble blue-light-emitting copper nanoclusters (CuNCs) were prepared by polyvinylpyrrolidone (PVP) and ascorbic acid as templating and reducing agents, respectively. The optimization of synthesis conditions of PVP-CuNCs were studied and analyzed. And the quantum yield of the PVP-CuNCs was calculated to be 14.97%. It had good specificity and exceptionally sensitive detection for sodium dichloroisocyanurate (DCCNa)/rosmarinic acid (RA), with a linear response range of 0.030-2.400/0.030-0.900 µM and corresponding LOD value of 10.766/8.985 nM. Moreover, the fluorescent reaction mechanisms of the PVP-CuNCs-DCCNa and PVP-CuNCs-DCCNa-RA systems were discussed, and the sensing probe could be effectively used for the assays of DCCNa and RA in genuine samples, whose results were acceptable.

Selective nitridation-corrosion process to recover vanadium, titanium, chromium, and iron from vanadium slag.

Vanadium slag (V-slag) is an important secondary V source, but other valuable elements are discarded in the tailings in industry. Herein, a green nitridation-corrosion process is proposed for the comprehensive recovery of valuable elements (V, Ti, Cr, Fe) from V-slag without producing hazardous waste. Thermodynamic results indicate that ammonia gas (NH3) can selectively reduce Fe and nitride V, Cr, and Ti. The main phase composition of the nitrided V-slag included metallic Fe, nitrides, and diopside under optimal conditions, and their relative contents were 42.5, 26.2, and 31.3%, respectively, after roasting at 1000 °C for 6 h. The effects of the main parameters on corrosion test were investigated, and the highest weight-gain ratio attained was 19.6%. FeOOH crystallizes on the surface of the nitrided V-slag due to the oxidization of metallic Fe. The phase evolution during the entire process is spinel/olivine/diopside → Fe/nitrides/diopside → FeOOH/nitrides/diopside. Owing to finer particle sizes, most FeOOH is separated by wet sieving (<1400 mesh). The purity of the enriched nitrides attained was 43% after pickling to remove excess Fe. The total recovery rates of Fe, V, Ti, Cr were 87.76%, 95.92%, 92.92%, 92.11%, respectively. This paper provides a sustainable strategy for the comprehensive utilization of V-slag, and guides the cleaner treatment of other similar minerals.

Species Identification of Caviar Based on Multiple DNA Barcoding.

This study aimed to explore the applicability of DNA barcoding for assessing the authenticity of caviar on the Chinese market. A set of universal COI primers and two sets of designed primers based on COI and D-loop genes were used to identify maternal species of samples from 21 batches of caviar. The results showed that the PCR products from three sets of primers had more than 98% similarity to the sequences in database. The COI gene could not distinguish sturgeons with closed genetic relationships, while D-loop gene could effectively improve the accuracy of DNA barcoding and was more suitable to the identification of interspecific sturgeon than the COI gene. The neighbor-joining dendrogram further confirmed the applicability and accuracy of COI and D-loop genes in identifying maternal relatives of caviar (Acipenser baerii/Acipenser gueldenstaedtii/Acipenser schrenckii/Huso dauricus/Huso huso). Despite the limitations of mitochondrial DNA in identifying hybrid sturgeon species, the presence of counterfeit caviar of non-sturgeon ingredients could be excluded. All the caviar samples were identified successfully as sturgeon species, but the mislabeling rate of species was 33.4%, indicating that there were illegal phenomena such as disorderly labeling, mislabeling, and adulteration on the market.

Identification of Robust and Key Differentially Expressed Genes during C2C12 Cell Myogenesis Based on Multiomics Data.

Myogenesis is a central step in prenatal myofiber formation, postnatal myofiber hypertrophy, and muscle damage repair in adulthood. RNA-Seq technology has greatly helped reveal the molecular mechanism of myogenesis, but batch effects in different experiments inevitably lead to misinterpretation of differentially expressed genes (DEGs). We previously applied the robust rank aggregation (RRA) method to effectively circumvent batch effects across multiple RNA-Seq datasets from 3T3-L1 cells. Here, we also used the RRA method to integrate nine RNA-Seq datasets from C2C12 cells and obtained 3140 robust DEGs between myoblasts and myotubes, which were then validated with array expression profiles and H3K27ac signals. The upregulated robust DEGs were highly enriched in gene ontology (GO) terms related to muscle cell differentiation and development. Considering that the cooperative binding of transcription factors (TFs) to enhancers to regulate downstream gene expression is a classical epigenetic mechanism, differentially expressed TFs (DETFs) were screened, and potential novel myogenic factors (MAF, BCL6, and ESR1) with high connection degree in protein-protein interaction (PPI) network were presented. Moreover, KLF5 cooperatively binds with the three key myogenic factors (MYOD, MYOG, and MEF2D) in C2C12 cells. Motif analysis speculates that the binding of MYOD and MYOG is KLF5-independent, while MEF2D is KLF5-dependent. It was revealed that KLF5-binding sites could be exploited to filter redundant MYOD-, MYOG-, and MEF2D-binding sites to focus on key enhancers for myogenesis. Further functional annotation of KLF5-binding sites suggested that KLF5 may regulate myogenesis through the PI3K-AKt signaling pathway, Rap1 signaling pathway, and the Hippo signaling pathway. In general, our study provides a wealth of untapped candidate targets for myogenesis and contributes new insights into the core regulatory mechanisms of myogenesis relying on KLF5-binding signal.

A Streptococcus aquaporin acts as peroxiporin for efflux of cellular hydrogen peroxide and alleviation of oxidative stress.

Aquaporins (AQPs) are transmembrane proteins widely distributed in various organisms, and they facilitate bidirectional diffusion of water and uncharged solutes. The catalase-negative bacterium Streptococcus oligofermentans produces the highest H2O2 levels reported to date, which has to be exported to avoid oxidative stress. Here, we report that a S. oligofermentans aquaporin functions as a peroxiporin facilitating bidirectional transmembrane H2O2 transport. Knockout of this aquaporin homolog, So-AqpA, reduced H2O2 export by ∼50% and increased endogenous H2O2 retention, as indicated by the cellular H2O2 reporter HyPer. Heterologous expression of So-aqpA accelerated exogenous H2O2 influx into Saccharomyces cerevisiae and Escherichia coli cells, indicating that So-AqpA acts as an H2O2-transferring aquaporin. Alanine substitution revealed Phe-40 as a key residue for So-AqpA-mediated H2O2 transport. Northern blotting, qPCR, and luciferase reporter assays disclosed that H2O2 induces a >10-fold expression of So-aqpA Super-resolution imaging showed that H2O2 treatment increases So-AqpA protein molecules per cell by 1.6- to 3-fold. Inactivation of two redox-regulatory transcriptional repressors, PerR and MntR, reduced H2O2-induced So-aqpA expression to 1.8- and 4-fold, respectively. Electrophoretic mobility shift assays determined that MntR, but not PerR, binds to the So-aqpA promoter, indicating that MntR directly regulates H2O2-induced So-aqpA expression. Importantly, So-aqpA deletion decreased oxic growth and intraspecies competition and diminished the competitive advantages of S. oligofermentans over the caries pathogen Streptococcus mutans Of note, So-aqpA orthologs with the functionally important Phe-40 are present in all streptococci. Our work has uncovered an intrinsic, H2O2-inducible bacterial peroxiporin that has a key physiological role in H2O2 detoxification in S. oligofermentans.

Comparison of interpolation-based sampling frequency offset compensation schemes for practical OFDM-VLC systems.

Sampling frequency offset (SFO) is an important issue in the orthogonal frequency-division multiplexing (OFDM)-based visible light communication (VLC) systems with low-cost analog-to-digital or digital-to-analog converters (ADCs/DACs). A digital interpolation or resampling filter can be used to effectively compensate the SFO. In such case, oversampling at the receiver ADC is required to mitigate the aliasing effect due to imperfect DACs and nonlinearity of visible light sources that cause extra frequency components inside/outside the OFDM signal spectrum. The oversampling factor (rate) is mainly determined by the order of the digital interpolation filter and nonlinear VLC links. The design of the OFDM-VLC receiver incorporating the digital interpolation filter is vital as it affects not only the transmission performance but also the complexity of digital signal processing (DSP). To evaluate the feasibility of the digital interpolation-based SFO compensation schemes for cost-sensitive VLC applications, in this paper, a real-time OFDM-VLC receiver incorporating the 2nd/3rd/4th order interpolation filters is experimentally demonstrated. An OFDM frame structure is designed for the synchronization including SFO estimation and compensation, in which the precision and latency of DSP are considered. On the basis of the real-time OFDM-VLC receiver, the comparison in the VLC transmission performance and DSP complexity between different interpolation-based SFO compensation schemes is discussed.

The transmissibility of hepatitis C virus: a modelling study in Xiamen City, China.

This study aimed at estimating the transmissibility of hepatitis C. The data for hepatitis C cases were collected in six districts in Xiamen City, China from 2004 to 2018. A population-mixed susceptible-infectious-chronic-recovered (SICR) model was used to fit the data and the parameters of the model were calculated. The basic reproduction number (R0) and the number of newly transmitted cases by a primary case per month (MNI) were adopted to quantitatively assess the transmissibility of hepatitis C virus (HCV). Eleven curve estimation models were employed to predict the trends of R0 and MNI in the city. The SICR model fits the reported HCV data well (P < 0.01). The median R0 of each district in Xiamen is 0.4059. R0 follows the cubic model curve, the compound curve and the power function curve. The median MNI of each district in Xiamen is 0.0020. MNI follows the cubic model curve, the compound curve and the power function curve. The transmissibility of HCV follows a decreasing trend, which reveals that under the current policy for prevention and control, there would be a high feasibility to eliminate the transmission of HCV in the city.

Epidemiological characteristics and transmissibility of shigellosis in Hubei Province, China, 2005 - 2017.

BACKGROUND: Shigellosis is one of the main diarrhea diseases in developing countries. However, the transmissibility of shigellosis remains unclear. METHODS: We used the dataset of shigellosis cases reported between January 2005 and December 2017, from Hubei Province, China. A mathematical model was developed based on the natural history and the transmission mechanism of the disease. By fitting the data using the model, transmission relative rate from person to person (b) and from reservoir to person (bw), and the effective reproduction number (Reff) were estimated. To simulate the contribution of b and bw during the transmission, we performed a "knock-out" simulation in four scenarios: A) b = 0 and bw = 0; B) b = 0; C) bw = 0; D) control (no intervention). RESULTS: A total of 130,770 shigellosis cases were reported in Hubei province, among which 13 cases were dead. The median annual incidence was 19.96 per 100,000 persons (range: 5.99 per 100,000 persons - 29.47 per 100,000 persons) with a decreased trend (trend χ2 = 25,470.27, P < 0.001). The mean values of b and bw were 0.0898 (95% confidence interval [CI]: 0.0851-0.0946) and 1.1264 × 10- 9 (95% CI: 4.1123 × 10- 10-1.8416 × 10- 9), respectively. The "knock-out" simulation showed that the number of cases simulated by scenario A was almost the same as scenario B, and scenario C was almost the same as scenario D. The mean value of Reff of shigellosis was 1.19 (95% CI: 1.13-1.25) and decreased slightly with a Linear model until it decreased to an epidemic threshold of 0.99 (95% CI: 0.65-1.34) in 2029. CONCLUSIONS: The incidence of shigellosis is still in high level. The transmissibility of the disease is low in Hubei Province. The transmission would be interrupted in the year of 2029.

Feasibility of containing shigellosis in Hubei Province, China: a modelling study.

BACKGROUND: The transmission features and the feasibility of containing shigellosis remain unclear among a population-based study in China. METHODS: A population-based Susceptible - Exposed - Infectious / Asymptomatic - Recovered (SEIAR) model was built including decreasing the infectious period (DIP) or isolation of shigellosis cases. We analyzed the distribution of the reported shigellosis cases in Hubei Province, China from January 2005 to December 2017, and divided the time series into several stages according to the heterogeneity of reported incidence during the period. In each stage, an epidemic season was selected for the modelling and assessing the effectiveness of DIP and case isolation. RESULTS: A total of 130,770 shigellosis cases were reported in Hubei Province. The median of Reff was 1.13 (range: 0.86-1.21), 1.10 (range: 0.91-1.13), 1.09 (range: 0.92-1.92), and 1.03 (range: 0.94-1.22) in 2005-2006 season, 2010-2011 season, 2013-2014 season, and 2016-2017 season, respectively. The reported incidence decreased significantly (trend χ2 = 8260.41, P <  0.001) among four stages. The incidence of shigellosis decreased sharply when DIP implemented in three scenarios (γ = 0.1, 0.1429, 0.3333) and when proportion of case isolation increased. CONCLUSIONS: Year heterogeneity of reported shigellosis incidence exists in Hubei Province. It is feasible to contain the transmission by implementing DIP and case isolation.

Discovery and optimization of novel N-benzyl-3,6-dimethylbenzo[d]isoxazol-5-amine derivatives as potent and selective TRIM24 bromodomain inhibitors with potential anti-cancer activities.

Tripartite motif-containing protein 24 (TRIM24), recognized as an epigenetic reader for acetylated H3K23 (H3K23ac) via its bromodomain, has been closely involved in tumorigenesis or tumor progression of several cancers. Developing inhibitors of TRIM24 is significant for functional studies and drug discovery. Herein, we report the identification, optimization and evaluation of N-benzyl-3,6-dimethylbenzo[d]isoxazol-5-amines as TRIM24 bromodomain inhibitors starting from an in house library screening. Structure-based optimization leads to two potent and selective compounds 11d and 11h in an Alphascreen assay with IC50 values of 1.88 µM and 2.53 µM, respectively. The viability assay demonstrates the great potential of this series of compounds as inhibitors of proliferation of prostate cancer (PC) cells LNCaP, C4-2B. A colony formation assay further supports this inhibitory activity. Compounds 11d and 11h inhibit cell proliferation of other cancer types such as non-small cell lung cancer (NSCLC) cells A549 with IC50 values of 1.08 µM and 0.75 µM, respectively. These data suggests that compounds 11d and 11h are promising lead compounds for further research.

Preconditioning rats with three lipid emulsions prior to acute lung injury affects cytokine production and cell apoptosis in the lung and liver.

BACKGROUND: Critically ill patients are at higher risk having acute lung injury (ALI) and more often in need of parenteral nutrition. We sought to study whether preconditioning with representative of lipid emulsions for one week could benefit rats from ALI. METHODS: Using a lipopolysaccharide (LPS)-induced ALI rat model and techniques such as polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. RESULTS: PGE2 production in the serum was highest in the LPS group, followed with Intralipid group, and the PGE2 level of these two groups was significantly (P < 0.05) higher than the rest. Intralipid conditioning caused significantly less production of LTB4 than the LPS, Clinoleic, or Omegaven group. In contrast to Intralipid, rats pretreated with Clinoleic or Omegaven significantly decreased their production of inflammatory mediators (IL-1 ß, IL-6 and TNF-α), had less apoptosis in the lung tissues, and Omegaven greatly improved liver function upon lipopolysaccharide (LPS) challenge. CONCLUSIONS: In an ALI setting, preconditioning with Omegaven or Clinoleic was better than Intralipid in decreasing the intensity of the cytokine storm and apoptosis caused by LPS challenge, and Omegaven in addition had the potential to improve liver function. The results from the present study set a basis for further investigation of the molecular mechanisms of ALI, including the up- and downstream pathways of proinflammatory factor production, in search of (small) molecules intervening with the pathogenesis of ALI in order to translate relevant research findings into clinical benefit for patients with ALI. The use of Omegaven or Clinoleic, particularly in patients with ALI, is still characterized by uncertainty due to a lack of relevant studies. Future investigations must specifically focus on the route of administration and mode of application (enteral vs. parenteral/bolus vs. continuous), determining an optimal dose of Omegaven or Clinoleic, and the defining the best timepoint(s) for administration. Critically ill patients are at higher risk having acute lung injury (ALI) and more often in need of parenteral nutrition. The effect of lipid emulsion via parenteral nutrition on liver function was first time evaluated in rats in an ALI setting. The comparison of three forms of lipid emulsion in a rat model of acute lung injury was first time studied. The fish oil-based lipid emulsion decrease in PGE 2 and increase in LTB 4 was first time reported.

Dynamic Liquid Surface Enhanced Raman Scattering Platform Based on Soft Tubular Microfluidics for Label-Free Cell Detection.

Cell detection is of great significance for biomedical research. Surface enhanced Raman scattering (SERS) has been widely applied to the detection of cells. However, there is still a lack of a general, low-cost, rapid, and sensitive SERS method for cell detection. Herein, a dynamic liquid SERS platform, which combines label-free SERS technique with soft tubular microfluidics for cell detection, is proposed. Compared with common static solid and static liquid measurement, the dynamic liquid SERS platform can present dynamical mixing, precise control of the mixing time, and continuous spectra collection. By characterizing the model molecules, the proposed dynamic liquid SERS platform has successfully demonstrated good stability and repeatability with 1.90% and 4.98% relative standard deviation (RSD), respectively. Three cell lines including one normal breast cell line (MCF-10A) and two breast cancer cell lines (MCF-7 and MDA-MB-231) were investigated in this platform. 270 cell spectra were selected as the training set for the classification of the models based on the K-Nearest Neighbor (K-NN) algorithm. In three independent experiments, three types of cells were identified by a test set containing 180 cell spectra with sensitivities above 83.3% and specificities above 91.6%. The accuracy was 94.1 ± 1.14% among three independent cell identifications. The dynamic liquid SERS platform has shown higher signal intensity, better repeatability, less pretreatment, and obtainment of more spectra with less time consumption. It will be a powerful detection tool in the area of cell research, clinical diagnosis, and food safety.