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Several long half-life natural and anthropogenic radionuclides, including 137Cs, 226Ra, 232Th, and 40K, in a 45 cm-long sediment core collected from the east continental shelf of Hainan Island, South China Sea, have been analyzed. The results showed that mean activity of 137Cs, 226Ra, 232Th, and 40K were 2.03 ± 1.2, 20.4 ± 1.8, 45.7 ± 3.0, and 520.0 ± 20.0 Bq/kg, respectively. Radium equivalent activity and External hazard index imply a low radiation, and the study area could serve as a background reference value for environmental radionuclides in east continental shelf of Hainan Island, South China Sea.

This study aimed to investigate the characteristics, moisture contents, chemical fingerprints changes and aflatoxins accumulation of Atractylodis rhizoma during storage, further to determine the optimum temperature and relative humidity conditions. Based on the suitable temperature (20–40 °C) and relative humidity (80–95%), 13 different temperature and humidity conditions were set up by the central composite design-response surface methodology (CCD-RSM) for Aspergillus flavus. After inoculation with Aspergillus flavus by artificial infection, A. rhizoma samples were stored under normal conditions and 13 different temperature and relative humidity levels. By taking the changes of characteristics, the contents of moisture, chemical fingerprints and aflatoxins as the evaluation indexes for A. rhizoma with or without Aspergillus flavus fungi to optimize the optimal storage conditions. After storage for 10 days, the color of A. rhizoma was deepened, the water content and chemical composition increased, and some unknown components were detected. The susceptible condition for aflatoxins production in A. rhizoma was identified at temperature 22–37 °C and relative humidity over 87.5%. Thus, the suitable storage conditions for A. rhizoma should be controlled at temperature below 20 °C and relative humidity less than 85%. This paper screened out the optimum temperature and humidity for the storage of A. rhizoma. Then, the storage specification for A. rhizoma was proposed, lying technical and data support for the scientific preservation of other food or herbs.

Hanying Shen,1 Lingling Jiang,1 Linlin Nie,1 Xiaohui Fan,1 Yanqiu Xu,1 Lingling Yin,2 Linyan Xu,1,3 Jieyun Xia,2 Zhenyu Li,1– 3 Feng Zhu,1– 3 Kailin Xu1– 3 1Blood Disease Institute, Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China; 2Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221002, People’s Republic of China; 3Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu, 221000, People’s Republic of ChinaCorrespondence: Feng Zhu; Jieyun XiaDepartment of Hematology, The Affiliated Hospital of Xuzhou Medical University, 99, West Huaihai Road, Quanshan District, Xuzhou, Jiangsu, 221002, People’s Republic of ChinaTel +86 516 8580 6985Fax +86 516 8580 1527Email frankfeng_2004@126.com; jieyunxia0315@163.comBackground: Originating from extranodal organs or tissues, primary extranodal lymphoma (PENL) acts in different primary sites with diverse clinical performances and PENL has remarkable geographical differences and lacks the relevant reports in each region.Patients and Methods: Two hundred and twenty PENL patients were enrolled, and the relevant clinical and laboratory indicators were analyzed. In addition, statistical methods were applied to analyze the effects of different factors on overall survival (OS) and progression-free survival (PFS) of patients.Results: The three most frequent primary sites of PENL are the digestive system, head and neck, and central nervous system. The patients were classified into groups based on their risk status, resulting in low-risk, medium-low-risk, medium-high-risk, and high-risk, and their respective 3-year OS values were calculated, which showed that 121 patients (55%) were in the low-risk group and 3-year OS was 85.2% (25.9% medium-low-risk, 3-year OS 66.6%; 15% medium-high-risk, 3-year OS 61.9%; 4.09% high risk, 3-year OS 45.7%). A multivariate analysis of the Cox regression demonstrated that serum beta 2-microglobulin (β2-MG) and lactate dehydrogenase (LDH) were independent prognostic factors for OS and PFS, respectively. Both the performance status and pathological subtypes were independent prognostic factors for OS and PFS.Conclusion: The correlated independent risk factors such as β2-MG, LDH, performance status, and pathological subtypes, were helpful for effectively determining the prognosis of PENL patients and guiding treatment.Keywords: beta 2-microglobulin, lactate dehydrogenase, performance status, pathological subtype, primary extranodal lymphoma, prognostic analysis

Berberine is an alkaloid from several medicinal plants originally used to treat diarrhea and dysentery as a traditional Chinese herbal medicine. In recent years, berberine has been discovered to exhibit a wide spectrum of biological activities in the treatment of diverse diseases ranging from cancer and neurological dysfunctions to metabolic disorders and heart diseases. This review article summarizes the clinical practice and laboratory exploration of berberine for the treatment of cardiometabolic and heart diseases, with a focus on the novel insights and recent advances of the underlying mechanisms recognized in the past decade. Berberine was found to display pleiotropic therapeutic effects against dyslipidemia, hyperglycemia, hypertension, arrhythmia, and heart failure. The mechanisms of berberine for the treatment of cardiometabolic disease involve combating inflammation and oxidative stress such as inhibiting proprotein convertase subtilisin/kexin 9 (PCSK9) activation, regulating electrical signals and ionic channels such as targeting human ether-a-go-go related gene (hERG) currents, promoting energy metabolism such as activating adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, modifying gut microbiota to promote transforming of berberine into its intestine-absorbable form, and interacting with non-coding RNAs via targeting multiple signaling pathways such as AMPK, mechanistic target of rapamycin (mTOR), etc. Collectively, berberine appears to be safe and well-tolerated in clinical practice, especially for those who are intolerant to statins. Knowledge from this field may pave the way for future development of more effective pharmaceutical approaches for managing cardiometabolic risk factors and preventing heart diseases.

Extracellular vesicles derived from trophoblasts (T-EVs) play an important role in pregnancy, but the mechanism is not entirely clear. In this study, we found that HLA-E, which is mostly confined to the cytoplasm of trophoblast cells, was secreted by T-EVs. The level of HLA-E in T-EVs from unexplained recurrent spontaneous abortion (URSA) patients was lower than that in normal pregnancy (NP) and RSA patients who had an abnormal embryo karyotype (AK-RSA). T-EVs promoted secretion of IFN-γ and VEGFα by decidual NK (dNK) cells from URSA patients via HLA-E, VEGFα was necessary for angiogenesis and trophoblast growth, and IFN-γ inhibited Th17 induction. Glycolysis and oxidative phosphorylation (OxPhos) were involved in this process. Glycolysis but not OxPhos of dNK cells facilitated by T-EVs was dependent on mTORC1 activation. Inhibition of T-EV production in vivo increased the susceptibility of mice to embryo absorption, which was reversed by transferring exogenous T-EVs. T-EVs promoted secretion of IFN-γ and VEGFα by dNK cells to maintain pregnancy via Qa-1 in abortion-prone mouse models. This study reveals a new mechanism of pregnancy maintenance mediated by HLA-E via T-EVs.

China is the world's largest rare earth producer and exporter, previous studies have shown that rare earth elements can cause oxidative damage in animal testis. However, the molecular mechanisms underlying these observations have yet to be elucidated. In this paper, male mice were fed with different doses (10, 20, and 40 mg/kg BW) of LaCl3 for 90 consecutive days, regulatory role of nuclear factor erythroid-2 related factor 2 (Nrf-2)/antioxidant response element (ARE) pathway in testicular oxidative stress induced by LaCl3 were investigated. Analysis showed that LaCl3 exposure could lead to severe testicular pathological changes and apoptosis in spermatogenic cells, it up-regulated the peroxidation of lipids, proteins and DNA, and induced the excessive levels of reactive oxygen species (ROS) production in mouse testis, reduced the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione S epoxide transferase (GST) as well as the glutathione (GSH) content. Furthermore, exposure to LaCl3 also downregulated the expression of Nrf2 and its target gene products, including heme oxygenase 1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), NAD(P)H dehydrogenase [quinine] 1(NQO1), protein kinase C (PKC), and phosphatidylinositol 3-kinase (PI3K), but upregulated the expression of Kelch-like ECH-related protein 1 (Keap1) in damaged mouse testes. Collectively, our data imply that the oxidative damage induced by LaCl3 in testis was related to inhibition of the Nrf-2/AREs pathway activation.

An extensive study collected in situ data along the Yellow Sea (YS) and East China Sea (ECS) to assess the radiometric properties and the concentration of the water constituents derived from Moderate Resolution Imaging Spectroradiometer (MODIS). Thirteen high quality match-ups were obtained for evaluating the MODIS estimates of Rrs(λ), chlorophyll a (Chi a) and concentrations of suspended particulate sediment matter (SPM). For MODIS Rrs(λ), the mean absolute percentage difference (APD) was in the range of 20%-36%, and the highest uncertainty appeared at 412 nm, whereas the band ratio of Rrs(λ) at 488 nm compared with that at 547 nm was highly consistent, with an APD of 7%. A combination of near-infrared bands and shortwave infrared wavelengths atmosphere correction algorithm (NIR-SWIR algorithm) was applied to the MODIS data, and the estimation accuracy of RIS were improved at most of the visible spectral bands except 645 nm, 667 nm and 678 nm. Two ocean-colour empirical algorithms for Chi a estimation were applied to the processed data, the results indicated that the accuracy of the derived Chi a values was obviously improved, the four-band algorithms outperformed the other algorithm for measured and simulated datasets, and the minimum APD was 35%. The SPM was also quantified. Two regional and two coastal SPM algorithms were modified according to the in situ data. By comparison, the modified Tassan model had a higher accuracy for the application along the YS and ECS with an APD of 21%. However, given the limited match-up dataset and the potential influence of the aerosol properties on atmosphere correction, further research is required to develop additional algorithms especially for the low Chi a coastal water.

Our previous studies have proved that 17β-hydroxysteroid dehydrogenase 4 (HSD17B4) is a novel proliferation-promoting protein. The overexpression of HSD17B4 promotes hepatocellular carcinoma (HCC) cell proliferation. Vitamin K2 (VK2), a fat-soluble vitamin, has the function of promoting coagulation and can inhibit the progression of liver cancer. A previous study demonstrated that VK2 could bind to HSD17B4 in HepG2 cells. However, the mechanism of VK2 in inhibiting HCC cell proliferation is not clear. In this study, we investigate whether VK2 can inhibit the proliferation of HCC cell induced by HSD17B4 and the possible mechanism. We detected the effect of VK2 on HSD17B4-induced HCC cell proliferation, and the activation of STAT3, AKT, and MEK/ERK signaling pathways. We measured the effect of HSD17B4 on the growth of transplanted tumor and the inhibitory effect of VK2. Our results indicated that VK2 directly binds to HSD17B4, but does not affect the expression of HSD17B4, to inhibit the proliferation of HCC cells by inhibiting the activation of Akt and MEK/ERK signaling pathways, leading to decreased STAT3 activation. VK2 also inhibited the growth of HSD17B4-induced transplanted tumors. These findings provide a theoretical and experimental basis for possible future prevention and treatment of HCC using VK2.

Supplying adequate nitrogen (N) to meet crop demand is critical for enhancing agricultural sustainability. Not only fertilizer N, but also N from other available sources should be considered in N supply capacity. We conducted a 10-year farming experiment using a split-plot design with two different main fertilizer management approaches and three N application strategies as add-on sub-treatments. Based on the experiment, we estimated the total N supply (TNsupply) for the summer maize cropping system, through considering environmental, soil, crop residue, and fertilizer N sources. An appropriate TNsupply was established by correlating TNsupply with the relative yield (RY), N input and output, and N use efficiency (NUE). The results revealed a wide variation in TNsupply (from 88 to 755 kg ha−1). The RY, N input, and N output fitted well to TNsupply using linear-plateau, linear, and linear-plateau models, respectively. The lower limits of TNsupply for achieving the maximum RY and N output were 361 and 358 kg ha−1, respectively. The relationship between N input and N output was described as linear-plateau. We determined the slope of the linear curve (55.4%) as the lower limit of NUE, beyond which the upper limit of TNsupply was determined to be less than 497 kg ha−1. Thus, appropriate TNsupply values ranged from 325 to 497 kg ha−1 for summer maize production, which could ensure enough N supply for higher yields and avoid excessive N input for higher NUE and lower environmental N loss. Our findings highlight that TNsupply can be an alternative indicator for evaluating N management.

Ultrafine Fe2O3 nanorods anchored on graphene oxide (GO) are synthesized by a one-pot route under mild conditions in presence of KMnO4 and Ni foam. Ni foam is beneficial for the formation of Fe2O3 rather than FeOOH under otherwise the same conditions, while KMnO4 accelerates the hydrolysis of FeCl3, which promotes the nucleation of Fe2O3 and the achievement of uniform ultra-small morphology thereby. As an anode material for lithium-ion batteries, the Fe2O3/GO manifests a reversible capacity of 1004 mA h g−1after 500 cycles at 200 mA g−1, and even presents a high reversible capacity of 722 mA h g−1 at 1600 mA g−1. The excellent electrochemical properties of Fe2O3/GO are attributed to the ultrafine nanorods of Fe2O3 and the strong interaction between Fe2O3 and GO, which can reduce the diffusion distance of Li+ ions, enlarge the electrode/electrolyte contact area and improve the cyclic stability of iron oxide.

Activin A, a member of the transforming growth factor-beta (TGF-β) superfamily, contributes to tissue healing and fibrosis. As the innate tissue cells, fibroblasts also play an important role in wound healing and fibrosis. Herein, this study was aimed to investigate how activin A exhibited regulatory effects on adhesion and migration of fibroblasts. We found that activin A induced the migration of fibroblast cell line L929 cells in transwell chamber and microfluidic device. Activin A also promoted L929 cells adhesion, but did not affect L929 cells viability or proliferation. In addition, activin A induced α-SMA expression and TGF-β1 release, which were factors closely related to tissue fibrosis, but had no effect on IL-6 production, a pro-inflammatory cytokine. Furthermore, activin A elevated calcium levels in L929 cells and increased p-ERK protein levels. Activin A-induced migration of L929 cells was attenuated by ERK inhibitor FR180204. To conclude, these data indicated that activin A as a novel chemokine induced the chemotactic migration of L929 cells via ERK signaling and possessed the pro-fibrosis role. These findings provide a new insight into understanding of activin A in tissue fibrosis.

Nanoscale zero-valent iron (nZVI) modified by cationic polyquaternium-7 (M550-nZVI) or anionic carboxymethyl cellulose (CMC-nZVI) were freshly synthesized, and followed by the successful applicability for the stabilization of Cr(VI) in soil. Scanning electron microscope (SEM) showed that the sizes of M550-nZVI and CMC-nZVI were 42–170 nm and 66–200 nm, respectively. X-ray diffraction (XRD) confirmed the presence of Fe0 and Fe3C in the as-synthesized composites. The kinetics were well fitted with pseudo-second order model (R2 > 0.99), indicating that the process was principally chemical reduction. Additionally, we observed that M550-nZVI had better resistance to oxidation than that of CMC-nZVI. Besides, RSM experiments showed that acetate ion (AA) could promote the Cr(VI) removal but humic acid ion (HA) and carbonate ion (CA) resulted in negative effects. Moreover, the modeling predication revealed that the optimum Cr(VI) removal of 92.44% by CMC-nZVI was available, being 22.52% higher than that of M550-nZVI. In conclusion, this work demonstrated that the inoxidizability of M550-nZVI had a dominant advantage, while CMC-nZVI had the more excellent reactivity than M550-nZVI. We believe that our conducted research work will open the new avenues for effective removal of heavy metals from the soil.

Oocyte IVM technology is an option for fertility preservation in some groups of patients, such as those with polycystic ovary syndrome, patients with ovarian hyperstimulation syndrome, and for patients with cancer. However, the developmental potential of oocytes from IVM still needs to improve. Several previous studies have reported that lysophosphatidic acid (LPA) promotes glucose metabolism, cumulus cell (CC) expansion, and oocyte nuclear maturation. However, the effect of LPA on oocyte cytoplasmic maturation, particularly mitochondrial function, has rarely been studied and the underlying mechanism is largely unknown, which impedes (pre)clinical applications of LPA. In this study, cumulus-oocyte complexes (COCs) and cumulus-denuded germinal vesicle oocytes (DOs) were treated with various concentrations of LPA during IVM, in the presence or absence of the oxidative stressor cyclophosphamide (CTX). In both normal and CTX-damaged COCs, the 25 μM LPA group exhibited improved CC expansion capacity, a higher nuclear maturation rate, and superior mitochondrial function, compared to no LPA treatment. When the concentration of LPA was over 40 μM, detrimental effects of LPA on oocyte maturation occurred. Compared with COCs, the addition of LPA slightly improved oocyte nuclear and cytoplasmic maturation of DOs, but this was not statistically significant. We observed that LPA promotes the activation of extracellular signal-regulated kinase (ERK)1/2, although this was not statistically significant in DOs. Furthermore, LPA could not reverse the negative effect of CC expansion and mitochondrial function after inactivation of ERK1/2 by U0126. RNA-sequencing and RT-PCR results showed that LPA upregulated several ERK1/2 downstream genes related to CC expansion, such as Areg, Cited4, and Ptgs2. This study demonstrates that LPA improves oocyte quality during IVM through the activation of ERK1/2 pathway CCs and oocytes, which provides evidence for the potential addition of LPA to IVM medium.

Fibroblasts play an important role in inflammation and tissue fibrosis. Both activin A and TNF-α can activate immune cells, however, the roles and relationship of them in activating fibroblasts in inflammation remain unclear. Here, this study revealed that TNF-α promoted the release of NO and IL-6 by L929 fibroblast cells, but co-treatment with activin A attenuated these effects. In contrast, activin A induced cell migration and increased the production of tissue fibrosis-related TGF-β1 and fibronectin, while TNF-α inhibited these function changes of L929 cells induced by activin A. Moreover, this study revealed that activin A and TNF-α regulated the activities of L929 cells via ERK1/2/MAPK pathway, rather than Smad3-dependent signaling pathway. Taken together, these data indicate that activin A and TNF-α exert mutually antagonistic effects on regulating fibroblasts activities, and the balance between their action may determine the process and outcome of fibroblasts-mediated inflammation.

A kind of biosurfactant rhamnolipid modified zero-valent iron nanoparticles have been synthesized and applied to evaluate the immobilization efficiency of Ni (Ⅱ) contaminated soil at three concentration levels (200Ni, 600Ni and 1800Ni). The results of SEM and XRD were clearly indicative of the well-attached phenomenon of rhamnolipid on the nZVI, featuring better stability and dispersity, and FTIR analysis proposed the interactions between rhamnolipid and nZVI through monodentate chelating between carboxylate groups and nZVI or hydrogen bonding with Fe-O groups on the surface. Sequential extraction procedures (SEP) analysis illustrated that the majority of labile fractions had been transformed into less accessible fractions (Fe-Mn oxide-bound fractions and residual fractions) after 28 days of incubation. And for low-concentrations polluted soil, soil self-remediation played a dominant role, while RL@nZVI exhibited a more significant stabilizing effect for medium and high-concentrations pollution. Furthermore, XPS and XRD analyses of Ni-adsorbed RL@nZVI identified the formation of NiO, Ni(OH)2 and revealed the possible interaction mechanisms including reduction, adsorption and precipitation/co-precipitation. These results confirmed that RL@nZVI presented a promising prospect for the immobilization of Ni polluted soil.

A major side effect of aminoglycoside antibiotics is mammalian hair cell death. It is thus intriguing that embryonic chick hair cells treated with aminoglycosides at embryonic day (E) 12 are insensitive to ototoxicity. To exclude some unknown factors in vivo that might be involved in preventing aminoglycoside damage to embryonic hair cells, we first cultured chick embryonic basilar papilla (BP) with an aminoglycoside antibiotic in vitro. The results indicated that the hair cells were almost intact at E12 and E14 and were only moderately damaged in most parts of the BP at E16 and E18. Generally, hair cells residing in the approximate and abneural regions were more susceptible to streptomycin damage. After incubation with gentamicin-conjugated Texas Red (GTTR), which is typically used to trace the entry route of aminoglycosides, GTTR fluorescence was not remarkable in hair cells at E12, was weak at E14, but was relatively strong in the proximal part of BP at E18. This result indicates that the amounts of GTTR that entered the hair cells are related to the degrees of aminoglycoside damage. The study further showed that the fluorescence intensity of GTTR decreased to a low level at E14 to E18 after disruption of mechanotransduction machinery, suggesting that the aminoglycoside entry into hair cells was mainly through mechanotransduction channels. In addition, most of the entered GTTR was not found to be colocalized with mitochondria even at E18. This finding provides another reason to explain why embryonic chick hair cells are insensitive to aminoglycoside damage.

A series of double scheelite-type tungstate green phosphors NaGd(WO4)2:Er3+, Tb3+ were synthesized by a hydrothermal route and subsequent calcination process, and they were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectrometry (EDS), photoluminescence spectroscopy and fluorescence lifetime measurements. The phosphors take on octahedral microcrystals with a mean side length of ~2 μm. In the single doped phosphors system, the energy transfer processes from WO42− to Er3+ or Tb3+ were discussed. The quenching concentrations of Er3+ and Tb3+ are 0.05 and 0.07, respectively. The critical distances for Er3+ and Tb3+ ions are calculated to be 14.28 A and 12.76 A, respectively. When doping Er3+/Tb3+ is applied in the single compound, the concentration quenching effect of Tb3+ ions occurs via a resonant-type dipole-dipole interaction as well as that of Er3+ ions. Under the excitation with ultraviolet (378 nm) or infrared (980 nm) light, the Er3+/Tb3+ co-doped NaGd(WO4)2 phosphors emit strong green emission. The obtained samples with bright emission intensity and appropriate decay time are suitable for use as green phosphors in the near ultraviolet LEDs and bioimaging applications.

In our previous work, it was found that the vesicles were formed spontaneously by mixing octyltriethylammonium bromide (C8 NE3 Br) with sodium dodecyl benzene sulfonate (SDBS), and the vesicles have been developed as a pseudostationary phase (PSP) in EKC. In the present work, the effects of the concentration and the molar ratio of cationic to anionic surfactant on the vesicle properties and the performances of vesicle PSP in EKC have been investigated. The aggregates at all mixing ratio were negatively charged regardless of which surfactant surplus. As C8 NE3 Br proportion increased, the microviscosity of the vesicle became larger. With the increase in the total surfactant concentration, the migration time window broadened at the molar ratio of C8 NE3 Br to SDBS of 3:7. Unexpectedly, the window became narrowed at molar ratio of 5:5 and 6:4. However, the methylene selectivity of vesicle PSP at all above-mentioned molar ratios enhanced as the total surfactant concentration increased, no matter whether the migration time window enlarged or narrowed. It implied that the vesicle PSP at molar ratio of 5:5 and 6:4 made it possible to obtain a better separation in a shorter time. When the total surfactant concentration was fixed at 20 mM, the methylene selectivity of the vesicle PSP of molar ratio of 5:5 was comparable to that of 3:7, but the migration time shortened by a half.

Saturated fatty acids (SFAs) induce reactive oxygen species (ROS) production in neurons. Extracellular signal regulated kinase (ERK)/nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) is a ROS response pathway. Therefore, high ROS is always accompanied by increase of HO-1, an anti-oxidative enzyme; but it remains unknown why there is no significant reduction of ROS with the increase of HO-1 in SFAs-treated neurons. We hypothesized that the up-regulation of HO-1 is compensatory for response to fatty acid-induced oxidative stress but not enough to reduce ROS levels. We evaluated the anti-ROS effect of HO-1 and the involved pathway in palmitic acid (PA)-treated human neuroblastoma BE(2)-M17 cells. As expected, PA-induced ROS increase was accompanied by activation of the ERK-Nrf2-HO-1 pathway, as demonstrated by an increase in ERK phosphorylation, Nrf2 phosphorylation and nuclear accumulation, and HO-1 expression at the mRNA and protein levels, in a PA-dose-dependent manner. In contrast, administration of the ROS scavenger NAC significantly reduced the levels of PA-regulated ROS and HO-1 protein. However, the ERK inhibitor U0126 not only reversed the activating effect of PA on the ERK-Nrf2-HO-1 pathway but also aggravated PA-induced ROS. Furthermore, the Nrf2-specific activator NK-252 significantly increased PA-up-regulated HO-1 protein and alleviated PA-induced ROS. Therefore, our results suggest that up-regulation of HO-1 in PA-treated neurons is a compensatory response to ROS increase and that increasing HO-1 expression by Nrf2 activation can prevent the process of ROS production in PA-treated neurons.

As a novel brominated flame retardant (NBFR), decabromodiphenyl ethane (DBDPE) has been poorly understood for the environmental fate and toxicity in terrestrial invertebrates. For the first time, the bioaccumulation, elimination, metabolism and detoxification of DBDPE in earthworms as well as its potential impacts on soil microbes were investigated. The results showed much higher DBDPE concentrations in casts than in earthworms. The bioaccumulation factor (BAF) and elimination rate constant (ke) values were 0.028–0.213 (gdw, worm/gdw, soil) and 0.323–0.452 (day−1), respectively. The detoxifying enzymes (CYP450 and GST) could be induced by DBDPE within the range of exposure dosage, and the activities were significantly increased at 21 d (p

When measuring reflectance spectra, it is very important to accurately extract chlorophyll fluorescence from elastic- scattering light in water-leaving radiance. The elastic scattering of light by water particles produces partially polarized light. In contrast, chlorophyll fluorescence in planktonic algae yields completely unpolarized light. These properties can be used to separate fluorescent signals from the water-leaving radiance and thus to determine chlorophyll concentration. The algal species Aureococcus anophagefferens was used to conduct a laboratory polarization experiment. For the tests, we used a field spectroradiometer and a polarizer; measurements were collected using two different observation modes. The chlorophyll fluorescence curve extracted through polarization shows an excellent match with the results obtained using the fluorospectro photometer for both measurement modes, suggesting that polarization-based chlorophyll fluorescence extraction may be feasible. The extracted fluorescence is more reliable at incident zenith angles ranging from 30° to 60°. For algae-containing water, the results improve with increasing chlorophyll concentration. This method could help improve chlorophyll concentration measurement and the remote-sensing detection of resulting harmful algae blooms.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background Auxin conjugates are hydrolyzed to release free auxin to ensure defined cellular auxin levels or gradients within tissues for proper development or response to environmental signals. The auxin concentration in the abscission zone (AZ) is thought to play an important role in mediating the abscission lag phase. Results In this study, the full cDNA sequences of seven tomato ILR1-like SlILL genes were identified and characterized, All SlILLs were found to have auxin conjugate hydrolysis activity. The effects of different auxin conjugates on abscission identified IAA-Ile as a candidate to determine the auxin conjugate and auxin conjugate hydrolysis functions in abscission. Treatment of pedicel explants with IAA-Ile for different times showed that application before 6 h could effectively delay abscission. IAA-Ile pre-incubation for 2 h was sufficient to inhibit abscission. These results showed that there is not sufficient auxin conjugates in the AZ to inhibit abscission, and the optimal time to inhibit abscission by the application of exogenous auxin conjugates is before 6 h. Treatment with cycloheximide (CHX, a protein biosynthesis inhibitor) indicated that de novo synthesis of auxin conjugate hydrolases is also required to delay abscission. During abscission, SlILL1, 5, and 6 showed abscission-related gene expression patterns, and SlILL1, 3, 5, 6, and 7 showed increasing expression trends, which collectively might contribute to delay abscission. Silencing the expression of SlILL1, 3, 5, 6, and 7 using virus-induced gene silencing showed that SlILL1, 5, and 6 are major mediators of abscission in tomato. Conclusions In the process of abscission, auxin inhibition is concentration dependent, and the concentration of auxin in the AZ was regulated by hydrolyzed auxin conjugates. SlILR1, 5, and 6 play a key role in flower pedicel abscission. Electronic supplementary material The online version of this article (10.1186/s12870-019-1840-9) contains supplementary material, which is available to authorized users.

The backscattering properties of four marine phytoplankton from three size-classified taxa at different chlorophyll concentrations were directly measured in the laboratory using a Hydroscat-6 instrument. The ancillary parameters measured included the absorption and scattering coefficients, chlorophyll-a concentration, cell size, and cell concentration. We found that the value of the backscattering coefficients at each band increased with an increase in chlorophyll concentration for each alga, and the spectral shape at the blue bands were changed for the picophytoplankton and nanophytoplankton while it remained the same for microphytoplankton with changes in the chlorophyll-a concentration. We also found that the backscattering variation range changed with the increase in the chlorophyll concentration: the larger the cell size, the smaller its range of change. In addition, the smaller particles had relatively higher backscattering at shorter wavelengths, but no relationship between the cell size and contribution to the backscattering was found. Moreover, we also found a relationship between size and both the backscattering ratio and backscattering cross-section, in accordance with previous results. The results from this work provide a good foundation for improving the accuracy of identifying red tide algae using water color remote sensing.

Hair cells can be regenerated after damage by transdifferentiation in which a supporting cell directly differentiates into a hair cell without mitosis. However, such regeneration is at the cost of exhausting the support cells in the mammalian mature cochlea. Thus, more effective methods should be found to promote mitotic regeneration but partially preserve support cells after damage. To address the issue, we first injured hair cells in the chick basilar papillae (BP) by treatment with streptomycin in vitro. We then compared the mitotic regeneration on the neural side in the middle part of BP after treatment with a pharmacological inhibitor or agonist of the Notch (DAPT), Wnt (LiCl), Bmp (Noggin) or Fgf (SU5402) signaling pathway, with that after treatment with combinations of two or three inhibitors or agonist of these pathways. Our results indicate that treatments with a single inhibitor or agonist of the Notch, Wnt, Bmp or Fgf signaling pathway could significantly increase mitotic regeneration as well as direct transdifferentiation. The results also show that hair cells (Myosin 7a+), support cells (Sox2+) and mitotically regenerated hair cells (Myosin 7a+/Sox2+/BrdU+) increased significantly on the neural side in the middle part of BP after two or three combinations of the inhibition of Notch, Bmp or Fgf signaling pathway or the activation of Wnt signaling pathway, besides the reported coregulatory effects of Notch and Wnt signaling. The study of the effects of systematic combinations of pathway modulators provided more insight into hair cell regeneration from mitosis.

How the intestinal tract develops a tolerance to foreign antigens is still largely unknown. Here we report that extracellular vesicles (EVs) with TGF-β1-dependent immunosuppressive activity are produced by intestinal epithelial cells (IECs) under physiological conditions. Transfer of these EVs into inflammatory bowel disease (IBD) mice induced by dextran sulfate sodium salt decreases IBD severity by inducing regulatory T cells and immunosuppressive dendritic cells. In contrast, decreased endogenous EV production promotes IBD development. IECs produce EVs with increased levels of TGF-β1 upon IBD development in an ERK-dependent manner. Furthermore, these EVs tend to localize in the intestinal tract associated with epithelial cell adhesion molecule (EpCAM). Knockdown of EpCAM in vivo increases the severity of murine IBD, and the protective effect of EVs from IECs with decreased EpCAM on murine IBD is blunted. Therefore, our study indicates that EVs from IECs participate in maintaining the intestinal tract immune balance., The intestinal tract is continually exposed to foreign material and gut homeostasis is dependent on tolerance. Here, the authors show that extracellular vesicles released from intestinal epithelial cells stimulate T regulatory cells and immunosuppressive dendritic cells.

Morphine has been widely used as rescue treatment for heart attack and failure in humans for many decades. Relatively little has been known about the role of spinal opioid receptors in morphine cardioprotection. Recent studies have shown that intrathecal injection of morphine can reduce the heart injury caused by ischemia (I)/reperfusion (R) in rats. However, the molecular and cellular mechanisms underlying intrathecal morphine cardioprotection has not been determined. Here, we report that intrathecal morphine postconditioning (IMPOC) rescued mean artery pressure (MAP) and reduced myocardial injury in I/R. Pretreatment with either naloxone (NAL), a selective mu-opioid receptor antagonist, or nitric oxide synthase (NOS) inhibitors via intrathecal delivery completely abolished IMPOC cardioprotection, suggesting that the spinal mu-opioid receptor and its downstream NOS signaling pathway are involved in the mechanism of the morphine-induced effect. Consistent with this, IMPOC significantly enhanced spinal neural NOS phosphorylation, nitric oxide, and cGMP content in a similar time course. Intrathecal application of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a specific inhibitor of guanylate cyclase, completely ablated IMPOC-induced enhancement of cardioprotection and spinal cGMP content. IMPOC rescue of MAP and ischemic injury is correlated with IMPOC enhancement of NOS signaling. Collectively, these findings strengthen the concept of spinal mu-opioid receptors as a therapeutic target that mediates morphine-induced cardioprotection. We also provide evidence suggesting that the activation of spinal NOS signaling is essential for morphine cardioprotection.

A multiband and a single-band semianalytical model were developed to predict algae cell density distribution. The models were based on cell density (N) dependent parameterizations of the spectral backscattering coefficients,bb(λ), obtained fromin situmeasurements. There was a strong relationship betweenbb(λ) andN, with a minimum regression coefficient of 0.97 at 488 nm and a maximum value of 0.98 at other bands. The cell density calculated by the multiband inversion model was similar to the field measurements of the coastal waters (the average relative error was only 8.9%), but it could not accurately discern the red tide from mixed pixels, and this led to overestimation of the area affected by the red tide. While the single-band inversion model is less precise than the former model in the high chlorophyll water, it could eliminate the impact of the suspended sediments and make more accurate estimates of the red tide area. We concluded that the two models both have advantages and disadvantages; these methods lay the foundation for developing a remote sensing forecasting system for red tides.

Novel brominated flame retardants (NBFRs) are now ubiquitous in the environment with the extensive production and application. In the present study, pentabromotoluene (PBT), hexabromobenzene (HBB) and decabromodiphenyl ethane (DBDPE) were spiked into the sediments where mudsnails (Bellamya aeruginosa) were cultivated. In the 35-day enrichment process, the highest concentration of the three NBFRs measured in mudsnail is 2.0 mg/kg, 22 mg/kg and 5.2 mg/kg dry weight (dw), respectively. The average enrichment of NBFRs in viscera was about 3 times of pleopod with the same mass. Meanwhile, the parent mudsnails can transfer NBFRs to their offspring. The removal half-life of the three NBFRs was in the range of 2.6 and 5.7 days according to the first-order kinetic equation. Several degradation products of the NBFRs were detected in mudsnail samples, which were exposed to single substance. 2,4,6-tribromotoluene was identified as degradation product of PBT; 1,2,4,5-tetrabromobenzene and 1,2,4-tribromobenzene were identified as debromination products of HBB. Possible degradation pathways were further proposed. Additionally, mudsnails after exposed to 50 mg/kg of NBFRs were observed under a scanning electron microscope, indicating that shrinkage, tissue hyperplasia and perforation occurred on the visceral surface. Such damage might be related to the accumulation of more pollutants in mudsnails viscera. As one of the few studies to explore the biological process of NBFRs, our observation could provide a scientific basis for evaluating the environmental risks of NBFRs to benthic organisms.

We examined the effects of pheophytin a (Phe-a) on absorption properties of phytoplankton obtained from the red tide prone area of Dalian Bay in the North Yellow Sea, China, in June 2007 and July 2011. When the proportion of Phe-a relative to chlorophyll-a (Chl-a) increased, the absorption peak in the blue-violet region shifted from 438nm to 409nm. The relationship between blue-violet absorption maximum and Phe-a concentration is more tightly correlated than the relationship between blue-violet absorption maximum and Chl-a concentration. However, we found the opposite results for the red absorption maximum. These findings suggest that Phe-a mainly effects the blue-violet absorption maximum, while Chl-a primarily controls the red absorption maximum. Our results are determined by specific absorption coefficients of Phe-a and Chl-a in living algae cells. A multivariate linear regression analysis revealed that the specific absorption coefficients of Phe-a accounts for the absorption peaks at 407 nm and 673 nm, and specific absorption coefficient of Chl-a accounts for the absorption peaks at 440 and 673 nm, furthermore, the specific absorption coefficients of Phe-a are much larger than those of Chl-a in the blue-violet region, but they are lower in the red region.

Background Lipotoxicity contributes to diabetic myocardial disease. In this study, we investigated the lipid species contributing to lipotoxicity and the relationship with peroxisomal β-oxidation in the heart of diabetic mice. Methods Male C57BL/6 mice were randomly divided into a Diabetic group (intraperitoneal injection of STZ) and a Control group (saline). Cardiac function indexes [ejection fraction (EF%) and fractional shortening (FS%)] were evaluated by echocardiography. Morphological changes in the myocardial tissues and mitochondria were assessed by electron microscopy following hematoxylin and eosin staining. Blood myocardial injury indexes and lipids were measured using an automatic biochemical analyzer. Cardiac ATP levels were analyzed using a commercially available kit. mRNA levels of glucose transporter 4 (GLUT4), fatty acid binding protein 3 (FABP3), palmitoyl transferase 1α (CPT-1α), acyl-CoA oxidase 1 (AOX1), D-bifunctional protein (DBP), 3-ketoacyl-CoA thiolase A (THLA), uncoupling protein (UCP) 2 and UCP3 were investigated by quantitative reverse-transcription polymerase chain reaction. FABP3 protein expression was analyzed by Western blotting. Non-targeted metabolomics by LC-MS/MS was applied to evaluate profile of lipid metabolism in heart. Results Compared with controls, EF% and FS% were significantly reduced in diabetic mice. Furthermore, blood myocardial injury indexes and lipids, as well as myocardial mitochondrial cristae fusion were significantly increased. In the diabetic heart, GLUT4 expression was decreased, while expression of FABP3, CPT-1α, AOX1, DBP, THLA, UCP2 and UCP3 was increased, and ATP levels were reduced. In total, 113 lipids exhibited significant differential expression (FC > 2, P

Accumulating evidence has implicated that the activation of signal transducer and activator of transcription 3 (STAT3) contributes to the progression of liver cancer by affecting the expression of proliferation‑associated genes. A previous study reported that elevated levels of 17β‑hydroxysteroid dehydrogenase 4 (HSD17B4) are observed in patients with liver cancer. The current study investigated how upregulated HSD17B4 expression promoted the expression of proliferation‑associated genes in rats with liver cancer. HSD17B4 expression in rats with liver cancer was significantly increased compared with the control group as determined by reverse transcription‑quantitative polymerase chain reaction and western blot assays. Immunohistochemical results revealed that STAT3 activation was positively correlated with increased HSD17B4 expression in tumor tissues from patients with liver cancer. Western blot results further suggested that HSD17B4 overexpression increased STAT3 activation via the protein kinase B and the mitogen‑activated protein kinase/extracellular‑signal‑regulated kinase signaling pathways in HepG2 cells. The present study suggested that overexpression may promote HepG2 proliferation by enhancing expression of various downstream targets of STAT3. Targeted inhibition of HSD17B4 may describe a novel approach in the prevention and treatment of liver cancer.

Docosahexaenoic acid (DHA) biosynthesis in the liver is the most important source of extra-hepatic tissue DHA. However, the levels of DHA and DHA biosynthesis in the livers of animals with type 2 diabetes mellitus remain unknown. In the current study, we used type 2 diabetic rats induced by high-fat diets and low-dose streptozotocin (STZ, 25 mg/kg) to investigate DHA biosynthesis in the liver during type 2 diabetes mellitus. The serum and livers were collected. Biochemical characteristics, fatty acid profiles, the activity of peroxisomal β-oxidation, and the expressions of enzymes involved in the DHA biosynthesis pathway were assayed in the liver of diabetic rats. The data showed that DHA levels were unexpectedly increased despite of the lower expressions of key enzymes, Δ5- and Δ6-desaturases (Δ5D and Δ6D) in the endoplasmic reticulum (ER). The increased DHA was accompanied by an increase in the expression of straight-chain acyl-CoA oxidase (SCOX), D-bifunctional protein (DBP), and 3-oxoacyl-CoA thiolase (THL), as well as elevated activity of peroxisomal β-oxidation and an increased capacity for DHA biosynthesis from C24:6n-3. These findings indicate that DHA biosynthesis is increased in the livers of diabetic rats induced by high-fat diets and STZ, and that this effect is related to increased activity of peroxisomal β-oxidation, but not of ER desaturases. 1 Practical applications The results support the hypothesis that the dietary supplementation in diabetes with DHA and EPA is desirable. The pathway of DHA biosynthesis in the liver of rats induced by high-fat diets and STZ is shown. DHA biosynthesis is increased in the livers of diabetic rats induced by high-fat diets and STZ, and this effect is related to increased activity of peroxisomal β-oxidation, but is not related to the activity of ER desaturases.

Anisodamine is an ancient Chinese medicine derived from Tibet as a belladonna alkaloid, which is usually used for improvement of blood circulation in patients with organ phosphorus poisoning or shock. In this study, for the first time, we report its cardioprotective effects on preventing ischemia/reperfusion (I/R) injury of patients with acute myocardial infarction (AMI), and decreasing the myocardial infarction area and severity in heart of Sprague-Dawley (SD) rats. Our results suggest a potential molecular mechanism of anisodamine against the I/R injury in cardiomyocytes is associated with its anti-apoptotic effect. Anisodamine treatment decreases the expression of caspase-3 and caspase-8, and increases Bcl-2/Bax ratio in cardiomyocytes. Our data suggest that anisodamine can provide significant cardioprotection against I/R injury, potentially through the suppression of cardiomyocytes apoptosis.

Hepatocellular carcinoma (HCC) arises in a setting of chronic inflammation induced by inflammatory cytokines, such as nuclear factor-kappaB (NF-κB). HCC is a male-predominant cancer that can be attenuated by estradiol (E2) in vitro and in vivo. Although 17β-hydroxysteroid dehydrogenase 4 (HSD17B4) has been implicated as an estradiol-inactivating enzyme, and its promoter sequence contains two putative NF-κB elements: it is currently unknown whether HSD17B4 is the link between inflammation, estradiol and proliferation in hepatoma cells. In this study, HepG2 cells were used to investigate the role of HSD17B4 in the proliferation of liver cancer cells treated with the NF-κB activator, tumor necrosis factor-alpha (TNF-α), with the inhibitor of NF-κB activation, pyrrolidinedithiocarbamate (PDTC), or with a related specific siRNA. We demonstrated that the human HSD17B4 gene is a target for NF-κB activation in inflammation-stimulated HepG2 cells. HSD17B4 is up-regulated via the binding of activated NF-κB to the distal NF-κB-responsive element via TNF-α stimulation, which then promotes cell proliferation by decreasing the levels of E2 and enhancing the expression of interleukin 6 (IL-6), cyclin D1 and proliferating cell nuclear antigen (PCAN). These results from HepG2 cells are consistent with the observation that HSD17B4 is highly expressed and activated NF-κB is highly co-localized with the NF-κB-responsive element of HSD17B4 in liver tumor tissues from HCC patients. Our findings indicate for the first time that HSD17B4 plays an important role in aggravated HCC progression and provides a novel therapeutic target for HCC.

Determining the level of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative DNA damage biomarker, is vital to the study of clinical pathogenesis and drug toxicity. The principal limitation of capillary electrophoresis (CE) with UV detection is its low sensitivity. To overcome this shortcoming, we developed a micellar electrokinetic capillary chromatography (MEKC) with solid-phase extraction (SPE) for urinary 8-OHdG analysis. The sensitivity of MEKC-UV was improved using a reasonable UV system, injection mode, and SPE. The parameters affecting MEKC and SPE were also optimized. The calibration curve was linear within the range from 1 to 500 μg L(-1). The limits of detection and quantification were 0.27 μg L(-1) and 0.82 μg L(-1), respectively. Interday and intraday precision were both

UV spectrometry combined with principle component analysis (PCA) and partial least-squares regression (PLSR) was developed for analysis of extra virgin olive oil (EVOO)-vegetable oil (corn oil, soybean oil, and sunflower oil) blends adulteration. The results show that EVOO-vegetable oil blends, oil blends without EVOO, and oil blends with palm oil (PO) can be discriminated by PCA based on the first three principal components. In addition, the root mean squared error (RMSE) and coefficient of determination (R 2 ) of PLSR based on UV spectrometry for detecting EVOO content are 0.710 % and 0.863 for EVOO-corn oil blends, 0.001 % and 1.000 for EVOO-soybean oil blends, and 0.271 % and 0.981 for EVOO-sunflower oil blends, respectively. For detecting PO content, the RMSE ranged from 0.001 % to 0.656 % and the R 2 ranged from 0.853 to 1.000. Therefore, UV spectrometry coupled with PCA and PLSR could be a potential method to identify and quantify EVOO and adulterant (PO) in EVOO-vegetable oil blends.

To test the expression and localization of aquaporins 8 (AQP8) and 9 (AQP9) in human term fetal membranes and placenta in both oligohydramnios and normal amniotic fluid volume (AFV) groups and to explore the association between aquaporin expression and oligohydramnios. Real-time polymerase chain reaction and immunohistochemistry were used to determine AQP8 and AQP9 expression levels and localization in amnion, chorion, and placenta, respectively. In addition, compared with the normal AFV group, the expression levels of both AQP8 and AQP9 in amnion in oligohydramnios group were significantly decreased, while their expressions in placenta were significantly increased. The expression level of AQP9 was also significantly decreased in chorion, while that of AQP8 was unchanged. Both AQP8 and AQP9 may play an important role in water flow both in intramembranous absorption and in placental water transfer. Our study offers the potential therapeutic approach for oligohydramnios.

A new method was developed for determination of ketamine (KT) in urine and plasma samples by derivatization and gas chromatography-mass spectrometry. In this article, KT was first derivatized with sodium nitrite to volatile N-nitrosamines under acidic condition. Then the derivative had been identified by the mass spectra. The derivatization conditions including the amount of hydrochloric acid, the amount of sodium nitrite, reaction temperature, reaction time and the extraction reagents were optimized. Calibration curves were linear in the range of 0.04-20 μg mL(-1) for KT, and the limit of detection (LOD) and limit of quantitation (LOQ) were 0.01 μg mL(-1) and 0.04 μg mL(-1), respectively. The results of recovery indicated that the method had good precision and reproducibility. Compared with existing derivatization methods, this method provided a rapid, convenient, effective and low-cost way for gas chromatography method of KT quantification.

Degradation of ascorbic acid (AA) in Zhanhua winter jujube stored at selected temperatures under continuous light and darkness conditions was described by first-order kinetics and Weibull distribution function, and the temperature dependence of AA loss was studied by the Arrhenius equation. The high correlation coefficients (R 2 > 0.99) indicated the acceptability of Weibull model for predicting the degradation of AA. Activation energy was determined to be 10.586 and 11.868 kcal/mol under continuous light condition and 12.636 and 13.190 kcal/ mol under continuous darkness condition according to first-order and Weibull models, respectively. This study revealed that the loss of AA in continuous darkness was more temperature-dependent than the other samples. In continuous light, AA degradation may be favored even if at low temperatures. Therefore, a low temperature and continuous darkness condition is recommended to preserve AA content in jujube fruits during postharvest storage.

Alzheimer's disease (AD) is characterized by the accumulation of the β-amyloid peptide (Aβ), which is generated from sequential cleavages of the amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase. Fatty acid alterations in AD brains have recently received substantial attention. Because increased very long chain fatty acid (VLCFA) levels in AD brains imply that peroxisomal β-oxidation dysfunction may be associated with AD pathogenesis, we investigated the effects of impaired peroxisomal β-oxidation on Aβ generation in vivo and in vitro using thioridazine, a selective peroxisomal β-oxidation inhibitor. Under the experimental conditions, thioridazine caused VLCFA accumulation and increases in Aβ(40) content, APP immunoreactivity and APP(751+770) mRNA expressions in the rat cerebral cortex. A correlation analysis showed that the Aβ(40) levels were positively correlated with the cortex C(24:0) and C(26:0) levels. Additionally, the primary cerebral cortex neurons treated with this compound showed increases in APP(751+770) mRNA, APP protein, BACE1 mRNA and protein, and secreted Aβ40 levels. This work supports an emerging viewpoint that impaired peroxisomal function may play an important role in the progression of AD pathology.

Activated T cells release bioactive Fas ligand (FasL) in exosomes, which subsequently induce self-apoptosis of T cells. However, their potential effects on cell apoptosis in tumors are still unknown. In this study, we purified exosomes expressing FasL from activated CD8+ T cell from OT-I mice and found that activated T cell exosomes had little effect on apoptosis and proliferation of tumor cells but promoted the invasion of B16 and 3LL cancer cells in vitro via the Fas/FasL pathway. Activated T cell exosomes increased the amount of cellular FLICE inhibitory proteins and subsequently activated the ERK and NF-κB pathways, which subsequently increased MMP9 expression in the B16 murine melanoma cells. In a tumor-invasive model in vivo, we observed that the activated T cell exosomes promoted the migration of B16 tumor cells to lung. Interestingly, pretreatment with FasL mAb significantly reduced the migration of B16 tumor cells to lung. Furthermore, CD8 and FasL double-positive exosomes from tumor mice, but not normal mice, also increased the expression of MMP9 and promoted the invasive ability of B16 murine melanoma and 3LL lung cancer cells. In conclusion, our results indicate that activated T cell exosomes promote melanoma and lung cancer cell metastasis by increasing the expression of MMP9 via Fas signaling, revealing a new mechanism of tumor immune escape.

Artificial neural network (ANN) and partial least-squares regression (PLSR) models were developed to predict the changes of anthocyanin (AC), ascorbic acid (AA), total phenols (TP), total flavonoid (TF), and DPPH radical scavenging activity (SA) in bayberry juice during storage based on fractal analysis (FA) and red, green, and blue (RGB) intensity values. The results show the root mean squared error (RMSE) of ANN-FA decreased 2.44 and 12.45% for AC (RMSE = 18.673 mg/100 mL, R(2) = 0.939) and AA (RMSE = 8.694 mg/100 mL, R(2) = 0.935) compared with PLSR-RGB, respectively. In addition, PLSR-FA (RMSE = 5.966%, R(2) = 0.958) showed a 12.01% decrease in the RMSE compared with PLSR-RGB for predicting SA. For the prediction of TP and TF, however, both models showed poor performances based on FA and RGB. Therefore, ANN and PLSR combined with FA may be a potential method for quality evaluation of bayberry juice during processing, storage, and distribution, but the selection of the most adequate model is of great importance to predict different nutritional components.

Diabetes mellitus correlates with subsequent development of Alzheimer's disease (AD). An accumulation of very long chain fatty acids (VLCFAs) was observed in AD brains. We found previously that inhibiting peroxisomal β-oxidation by an inhibitor caused increases in VLCFA and β-amyloid peptide (Aβ) in the cortex and primary cultured neurons of rats. Therefore, we investigated whether there was an impaired peroxisomal β-oxidation and elevated VLCFA related to the increased Aβ in the diabetic brain. This study was conducted in a type 2 diabetic rat model induced by a high-fat diet and low-dose streptozotocin. A decrease in peroxisomal β-oxidation activity caused by down-regulated thiolase expression and a consequent increase in C26:0 were observed. Meanwhile, decreases in eicosapentenoic acid (EPA) and increases in oxidative stress [indicated by levels of malondialdehyde (MDA), and the protein expression of NOX4, p47(phox) and HO-1], Aβ, and the expression of AβPP and BACE1, two proteins involved in Aβ production, were observed. C26:0 levels were positively correlated with Aβ and MDA. This work suggests that in addition to decreases in EPA, increases in C26:0 by impaired peroxisomal β-oxidation can be a potential risk factor contributing to the progression of AD in diabetic brains via inducing oxidative stress.

Rationale: Cardiac fatty acid-binding protein (FABP3) is a cardiac-specific member of lipid-binding protein family and its expression level is often reduced in patients with diabetic heart diseases. Recent evidence suggests that FABP3 suppresses calcium transient and shortening of isolated rat cardiomyocytes. However, the underlying mechanisms are largely elusive. Objective: To determine the role of FABP3 in regulating SR calcium release. Results: In STZ-induced type I diabetes mouse model (DM), protein expression level of FABP3 was elevated, cardiac function was reduced and negatively correlated with FABP3 expression level. Amplitudes of cell shortening and calcium transient are both impaired in DM cardiomyocytes, which can be mimicked by applying FABP3 at pathological concentration to control cardiomyocytes. FABP3 reduces calcium transient amplitude of cardiomyocytes in a dose dependent manner (EC50 = 0.052 nmol/L). SR calcium content is reduced in DM cardiomyocytes and FABP3 depletes SR calcium content in cardiomyocytes. FABP3 colocalizes with SERCA, inhibits SERCA activity with a greater EC50 (0.49 nmol/L). Co-immunoprecipitation study suggests elevated FABP3 promotes binding between SERCA and phospholamban. FABP3 also colocalizes with RyR2, binds to RyR2 and promotes RyR2-mediated SR calcium leak. Conclusion: Increased FABP3 expression level in DM mice compromises cardiac function by reducing SR calcium load via two independent approaches: (A) to reduce SERCA activity by promoting PLB-SERCA interaction and (B) to enhance RyR2-mediated SR calcium leak.

Aims Several studies have shown associations between the composition of polyunsaturated fatty acids (PUFAs) in various tissues and type 2 diabetes mellitus (T2DM) development in European populations. Genetic variants of fatty acid desaturase (FADS) contribute to the variations of PUFA composition. Here we have explored whether similar correlations are also true among Chinese Han people. Methods A case–control study was employed to examine this correlation in Han Chinese people. The study included 421 healthy adults and 331 T2DM patients. Results The ratio of arachidonic acid/linoleic acid (AA/LA), which reflects Δ6 desaturase activity, was significantly increased in T2DM patients. Furthermore, the ratio of eicosapentaenoic acid/α-linolenic acid (EPA/ALA), which reflects Δ5 desaturase activity, was markedly decreased in T2DM patients. Importantly, among four single nucleotide polymorphisms (rs174545, rs2072114, rs174602 and rs174616) in the FADS1-FADS2 gene cluster, only minor allele (T) of rs174616 was associated with decreased risk of T2DM in both codominant and dominant models after adjustment for age, gender and BMI. Furthermore, the ratio of AA/LA in both controls and T2DM was reduced in T carriers while an increased proportion of LA was seen in T2DM patients compared with control patients. Conclusion These data suggest that in northern Han Chinese people, the minor allele (T) of rs174616 in the FADS1-FADS2 gene cluster is associated with a decreased conversion rate of LA to AA, which may contribute to decreased reduced risk of developing T2DM.

Acyl-CoA oxidase (ACO) is the key enzyme that catalyzes the rate-determining step in the peroxisomal beta-oxidation of fatty acids. ACO catalyzes the oxidation of acyl-CoA with molecular oxygen to produce trans-2,3-dehydroacyl-CoA and H2O2. Given the participation of H2O2 in an enhanced chemiluminescent reaction with luminol, we have developed a novel "two-step" procedure for the quantitation of ACO activity by recording light emission using a chemiluminescence detector. A number of recommendations on standardizing the reaction conditions for the quantitative measurement of ACO-catalyzed reactions are offered. The proposed method is simple and reliable and has been successfully applied in the rat liver assay. The results indicate that ACO activities increased in the liver of type-2 diabetic rats but showed no significant change in the liver of insulin-resistant rat. A acil-CoA oxidase (ACO) é a enzima-chave que catalisa a etapa determinante da velocidade da beta-oxidação peroxissomal de ácidos graxos. A ACO catalisa a oxidação de acil-CoA com oxigênio molecular, produzindo trans-2,3-desidroacil-CoA e H2O2. Considerando a participação de H2O2 em uma reação quimiluminescente melhorada com luminol, nós desenvolvemos um procedimento de duas etapas novo para quantizar a atividade de ACO usando um detector de quimiluminescência para registrar a emissão de luz. São apresentadas várias recomendações de padronização das condições de reação para a medida quantitativa das reações catalizadas por ACO. O método proposto é simples e confiável, e foi aplicado com sucesso ao teste com fígado de rato. Os resultados mostraram que as atividades de ACO eram maiores no fígado de rato com diabetes tipo 2, mas não apresentaram alteração no fígado de rato resistente à insulina.

Ligand-activated Liver X Receptor (LXR) is known to increase cholesterol efflux from cells and reduce the production of amyloid β (Aβ) from amyloid-beta precursor protein (APP). However, little is known about the effects of LXRβ, one subtype of LXR, on endogenous Aβ. In this study, we show that LXRβ inactivation with specific antisense oligodeoxynucleotides (As-ODN) significantly reduced secreted Aβ and decreased mRNA levels of APP(751+770), and α-, β-secretase (ADAM10, BACE1) in primary rat neurons. We also show that As-ODN down-regulated the LXR responsive genes ABCA1 and HMG-CoA reductase (HMGCR). These changes are associated with decreased cellular cholesterol levels. The effect of LXRβ inactivation on Aβ levels is likely due to the alteration of cholesterol production and APP processing. Thus, our data suggest that LXRβ has an important function in cholesterol homeostasis and endogenous Aβ maintenance in neurons.