Exploring Cr(VI)-induced blood-brain barrier injury and neurotoxicity in zebrafish and snakehead fish, and inhibiting toxic effects of astaxanthin.

Cr(VI) is a common hazardous heavy metal contaminant that seriously endangers human and aquatic animal health. GPX4 was the key enzyme that reduces heavy metal toxicity through inhibiting ferroptosis pathway. Astaxanthin was GPX4 activator that can weaken biological toxicity induced by Cr(VI) exposure. The present study was conducted to evaluate the major role of GPX4 in astaxanthin protects Cr(VI)-induced oxidative damage, blood-brain barrier injury and neurotoxicity in brain-liver axis through inhibiting ferroptosis pathway. In the current study, astaxanthin intervention can effectively alleviate Cr(VI)-induced oxidative stress, blood-brain barrier damage, and neurotoxicity. GPX4 plays a major role in mediating astaxanthin nutritional intervention to reduce ROS and liver non-heme iron accumulation, which would contribute to the reduction of ferroptosis. Meanwhile, astaxanthin maintains the stability of transport receptors and protein macromolecules such as TMEM163, SLC7A11, SLC3A2, FPN1 and GLUT1 in the brain liver axis, promoting substance exchange and energy supply. Moreover, astaxanthin alleviates Cr(VI)-induced neurotoxicity by promoting tight protein expression and reducing blood-brain barrier permeability.

Polysaccharide from dandelion enriched nutritional composition, antioxidant capacity, and inhibited bioaccumulation and inflammation in Channa asiatica under hexavalent chromium exposure.

Taraxacum mongolicum polysaccharide (TMP) exhibits anti-inflammatory and antioxidant activity, making it an attractive candidate for aquatic-product-safety applications. Here, this study was aimed to investigate the effects of dietary TMP on the growth, nutritional composition, antioxidant capacity, bioaccumulation and inflammation in Channa asiatica under hexavalent chromium stress. The C. asiatica was randomly distributed into five groups: The first group served as the blank control group (CK), the subsequent groups were fed TMP-supplemented feed (0, 0.5, 1.0 and 2.0 g/kg), respectively, and exposed to waterborne Cr6+ for 28 days. Our results indicated that the TMP effectively increased (P < 0.05) C. asiatica muscle flavour amino acid, total free amino acids, monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and EPA + DHA contents, enhanced positively antioxidant enzyme activity (GPX, SOD, CAT, T-AOC), reduced oxidative stress parameters (MDA, PC), and up-regulated antioxidant-related genes mRNA expression. Meanwhile, the appropriate amount of TMP supplementation also inhibited the bioaccumulation of Cr6+ in tissues and alleviated the inflammatory response (P < 0.05). Furthermore, sensory evaluation implied that the overall score of sashimi and cooked fillet in the 2.0 g/kg TMP group was the highest in the experimental group, second only to CK. In brief, these results elucidate that TMP-supplemented diets excellently ameliorated the growth, enriched nutritional composition and antioxidant capacity, and inhibited bioaccumulation and inflammation in C. asiatica exposed to waterborne Cr6+.

Exploration of tissue distribution of ginsenoside Rg1 by LC-MS/MS and nanospray desorption electrospray ionization mass spectrometry.

Ginsenoside Rg1 (Rg1) was one of the dominent active components in several Panax medicinal species as Panax notoginseng and Panaxginseng with diversified bioactivities. However, the study on tissue distribution of Rg1 remained limited and needed to be further explored for elucidation of its spatial distribution. In the present study, a LC-MS/MS combined with nanospray desorption electrospray ionization (DESI) mass spectrometry method was developed for exploration of tissue distribution of Rg1 at different time points after intravenous administration to rats. Furthermore, a MS inlet-heat method was developed to improve the imaging efficacy of Rg1 in brain tissue. The results obtained from LC-MS/MS analysis indicated that kidney possessed the highest tissue concentration, followed by liver, lung, spleen, heart and brain. Meanwhile, the elimination of Rg1 was swift within 1 h. For the spatial distribution of Rg1 by DESI-MS, Rg1 mainly accumulated in the pelvis section of kidney. Meanwhile, the imaging result of brain implied that Rg1 might be distributed in the pons and medulla oblongata region of brain at 15 min after intravenous administration. It is anticipated that the data on tissue distribution of Rg1 could provide references for further probing its efficacy and drug development.

Localization of constituents for determining the age and parts of ginseng through ultraperfomance liquid chromatography quadrupole/time of flight-mass spectrometry combined with desorption electrospray ionization mass spectrometry imaging.

Ginseng has been used for prevention and treatment of disease for thousands of years in China and many other Asian countries. Phytochemical studies have indicated that ginsenosides, polysaccharides, alkaloids, and phenolic acids are the active constituents of ginseng. Main and branch roots of ginseng exhibit distinct bioactive behavior. Furthermore, the bioactive behavior of ginseng depends on its age. Traditional analysis is complex preparation and provides inadequate of chemical information of the original distribution of analytes. Therefore, in this study, ultraperformance liquid chromatography quadrupole/time of flight-mass spectrometry (UPLC-QTOF MS) and desorption electrospray ionization mass spectrometry imaging (DESI-MSI) combined with orthogonal partial least squares discriminant analysis were used to discriminate ginseng in different age and parts of ginseng, and profiled distribution of selected markers. The results indicated that UPLC-QTOF-MS and DESI-MSI could be used to determine the parts and age of ginseng. Fifteen variables including five of protopanaxatriol (PPT), four of protopanaxadiol (PPD), and six of other types were assumed as markers for different parts of ginseng. Moreover, four variables of PPT, four of PPD, and ten of other types were used to determine the age of ginseng samples. An analysis of localization of markers indicated that malonyl ginsenoside, including malonyl-ginsenoside Rb1, Rb2, Rc, and Rd was mainly distributed in the corks. Neutral ginsenoside Rg1, yesanchinoisde D, and chikusetsusaponin Iva were mainly distributed in the cork and phloem. Non-ginsenoside castanoside H, 20(S)-protopanaxatriol, unknown 2, saponin III and cistanoside C were distributed in all tissues. Ethyloleate, unknown 1 and monolinolein were distributed in the cork.

Auxiliary interferometer in an optoelectronic swept-frequency laser and its application to the measurement of the group refractive index.

An optoelectronic swept-frequency laser (SFL) is an optoelectronic feedback system that includes an auxiliary interferometer that can exert precise control over the optical frequency sweep. The arm-length difference (ALD) of the auxiliary interferometer directly affects the performance of the whole system. We established a theoretical model to choose the optimal ALD of an auxiliary interferometer in an optoelectronic SFL system using a frequency-modulated continuous-wave reflectometry experimental setup. The experimental results indicated that, based on our system, the optimal ALD was 7 m, which agreed with the theoretical analysis. As an example application, we implemented the proposed system for measurement of the group refractive index of a glass sample. A minimum measurement error of 0.12% was obtained with the ALD of 7 m.

Optical fiber sensor based on a cholesteric liquid crystal film for mixed VOC sensing.

This paper proposes a novel cholesteric liquid crystal (CLC) film-based dual-probe fiber sensor to monitor volatile organic compound (VOC) gas. The sensor consists of a 2×2 multimode fiber coupler, in which the two output fiber ends are covered by two types of CLC films (CLCF) with different pitches. It can be observed that the reflection peak wavelengths of CLCs shift to the red side as the VOC gas concentration increases. The sensitivities of the two CLCFs are 8.435 nm·L/mmol and 14.867 nm·L/mmol to acetone, 14.586 nm·L/mmol and 29.303 nm·L/mmol to ethanol, respectively. In addition, the dependence of the peak wavelength shift of CLCF on the total concentration of the acetone and ethanol mixed gas at different mixing ratios is measured. The linear relationships between the peak shift of CLCFs, the total mixed gas concentration and acetone/ethanol ratio are calculated using the least-squares method. Therefore, this proposed dual-probe fiber optic sensor can distinguish the concentrations of acetone and ethanol in a mixed gas of acetone and ethanol.

Fiber micro-tip temperature sensor based on cholesteric liquid crystal.

This Letter proposes and demonstrates a novel, miniature fiber-tip temperature sensor with a tapered hollow capillary tube (HCT) filled with glycerin and dye-doped cholesteric liquid crystal (CLC). The function of glycerin is to provide a surface anchoring force to control the uniform orientation of CLC molecules, so that the CLC in the tapered HCT can be considered as a mirrorless photonic bandgap (PBG) microcavity. An unambiguously identifiable PBG mode single peak appears in the emission spectra of the sensor. The CLC-based fiber-tip temperature sensor has a temperature sensitivity of -9.167nm/∘C, and the figure of merit can reach 67.4∘C-1. This sensor offers key features and advantages, including compactness, unambiguous identifiability, and biocompatibility, which can satisfy requirements of temperature measurement in various temperature sensing application fields and has great potential for biochemical detection at cell level. In addition, the CLC was integrated into the optical fiber terminal, and the PBG mode is excited, collected and transmitted by the multimode fiber coupler, which is reported for the first time, to the best of our knowledge.

A novel high power vacuum diode with a focusing electrode for effective operation in a low guiding magnetic field.

A novel diode featuring an annular cathode and a ring-shaped focusing electrode and operating in a low guiding magnetic field (GMF) has been developed. It was found that the breakdown threshold for a focusing electrode made of titanium was 140 kV/cm higher than a stainless steel electrode for the same operating conditions. Comparison of the diode current measured by a Rogowski coil and the beam current measured by a Faraday cup at the collector indicated that an intense relativistic electron beam was transmitted effectively even in a GMF of as low as 0.21 T. In addition, a photo of the cathode plasma and the targeting results indicated that the emission uniformity of the graphite cathode was satisfactory.

Class I PI3K inhibitor ZSTK474 attenuates experimental autoimmune neuritis by decreasing the frequency of Th1/Th17 cells and reducing the production of proinflammatory cytokines.

The Class I phosphatidylinositol 3-kinase inhibitor, 2-(2-difluoromethy lbenzimidazol-1-yl)-4,6-dimorpholino-1,3,5-triazine (ZSTK474), has anti-inflammatory and immunoregulatory properties. However, whether it can be used to treat Guillain-Barré syndrome (GBS)-a neuroinflammatory disorder-is unknown. We induced experimental autoimmune neuritis (EAN) in Lewis rats, an established model of GBS. Orally administered ZSTK474 decreased neurological deficits in the GBS model, as demonstrated by diminished inflammatory cell infiltration, and ameliorated demyelination of sciatic nerves. Additionally, ZSTK474 decreased the number of Th1/Th17 cells and levels of the proinflammatory cytokines interleukin (IL)-1α, IL-1ß, IL-17, IL-23, interferon-γ, and tumor necrosis factor-α. We propose that the phosphoinositide 3-kinase/AKT/mammalian target of rapamycin complex 1 (PI3K/AKT/mTORC1) pathway likely contributed to the neuroprotective effect of ZSTK474. ZSTK474 effectively decreases the frequency of Th1/Th17 cells, thereby reducing the production of proinflammatory cytokines and successfully alleviating the symptoms of EAN. Thus, the neuroprotective effect of ZSTK474 indicates its potential utility as anti-inflammatory therapy for GBS.

A pilot study on the characteristics of circulating T follicular helper cells in liver transplant recipients.

Circulating CD4+CXCR5+ T follicular helper cells (cTfh) have been demonstrated to be involved in B cell-mediated systemic autoimmune diseases and alloreactive responses following kidney transplantation; however, whether cTfh cells are involved in alloreactive responses after liver transplantation (LT) remains unclear. Our present study aimed to investigate the characteristics of cTfh, as well as CXCR3+CCR6-Tfh1, CXCR3-CCR6-Tfh2, and CXCR3-CCR6+Tfh17 subsets in liver allograft recipients. A total of 30 liver transplant recipients were enrolled in this study. The frequencies of cTfh, Tfh1, Tfh2, and Tfh17 subsets, and interleukin (IL)-21-producing Tfh cells in the circulating blood were analyzed by flow cytometry. The capacity of cTfh cells to help B cells differentiate into plasmablasts was determined one day before and one month after LT. The results revealed that the frequency of cTfh cells remained unaltered before and after LT. However, the frequency of the cTfh subsets (e.g., Tfh1 and Tfh2 cells) and B cells were reduced one month after LT. Functionally, the capacity of Tfh cells to produce IL-21 was reduced one month after LT. In addition, cTfh cells exhibited the capacity to help B cells differentiate into plasmablasts in an IL-21-dependent manner in vitro, which was reduced after LT, despite the unaltered production of IgM and IgG by plasmablasts. Thus, our data suggest that cTfh cells may be involved in alloreactive responses following LT via helping B cells differentiate into plasmablasts and plasma cells.

PD-L1 (Programmed Death Ligand 1) Protects Against Experimental Intracerebral Hemorrhage-Induced Brain Injury.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a neurologically destructive stroke, for which no valid treatment is available. This preclinical study examined the therapeutic effect of PD-L1 (programmed death ligand 1), a B7 family member and a ligand for both PD-1 (programmed death 1) and B7-1 (CD80), in a murine ICH model. METHODS: ICH was induced by injecting autologous blood into 252 male C57BL/6 and Rag1-/- mice. One hour later, ICH mice were randomly assigned to receive an intraperitoneal injection of vehicle, PD-L1, or anti-PD-L1 antibody. Neurological function was assessed along with brain edema, brain infiltration of immune cells, blood-brain barrier integrity, neuron death, and mTOR (mammalian target of rapamycin) pathway products. RESULTS: PD-L1 significantly attenuated neurological deficits, reduced brain edema, and decreased hemorrhage volume in ICH mice. PD-L1 specifically downsized the number of brain-infiltrating CD4+ T cells and the percentages of Th1 and Th17 cells but increased the percentages of Th2 and regulatory T cells. In the PD-L1-treated group, we observed an amelioration of the inflammatory milieu, decreased cell death, and enhanced blood-brain barrier integrity. PD-L1 also inhibited the mTOR pathway. The administration of anti-PD-L1 antibody produced the opposite effects to those of PD-L1 in ICH mice. CONCLUSIONS: PD-L1 provided protection from the damaging consequences of ICH.

Anti-N-Methyl-d-Aspartate receptor (NMDAR) encephalitis during pregnancy: Clinical analysis of reported cases.

OBJECTIVE: To analyze the clinical features of 13 pregnant patients with anti-N-Methyl-d-Aspartate receptor (NMDAR) encephalitis. MATERIALS AND METHODS: Retrospective review of thirteen reported cases was conducted for anti-NMDAR encephalitis patients during pregnancy. The clinical data were collected from papers published in PubMed prior to 16 February 2016. Statistical analysis of the data was performed, which encompasses the patients' age, past medical history, onset of symptoms, concomitant with ovarian teratomas, immunotherapy, outcomes of mothers and newborns. RESULTS: Thirteen cases were reported in 11 articles with a median age of 23 (interquartile range, 19-27) years old. There were eight cases in which the onset periods of gestation happened in the first trimester and five cases in the second trimester. Among 13 cases, five patients had a past medical history, one concomitant with autoimmune Graves' hyperthyroidism, one with bilateral ovarian teratomas removed history, one with anti-NMDAR encephalitis five years before pregnancy and two with psychiatric symptoms. Five patients were found with ovarian teratomas. Seven patients responded to first-line immunotherapy whereas all of two patients responded to second-line immunotherapy when the first-line immunotherapy failed. Following up all the 13 patients, most experienced a substantial recovery, except one had spasticity and dystonia in one hand, and one died of a superimposed infection. Three fetuses were miscarried or aborted in total. Most newborns were healthy, except two cases (2/10) with abnormal neurologic signs. CONCLUSIONS: Clinical analysis of the data indicates that most patients respond to first-line immunotherapy. A second-line immunotherapy is effective when first-line immunotherapy fails. It has also been found that most mothers and newborns can have good outcomes.

Altered circulating T follicular helper cell subsets in patients with psoriasis vulgaris.

Circulating T follicular helper (Tfh) cells in the blood are counterparts to conventional Tfh cells in germinal centres. Similarly to conventional Tfh cells, circulating Tfh cells provide helpful signals for B cells. Circulating Tfh cells can be divided into three subpopulations, including Tfh17 (CXCR3-CCR6+), Tfh1 (CXCR3+CCR6-), and Tfh2 (CXCR3-CCR6-) cells, based on differences in CXCR3 and CCR6 expression. Recent studies have demonstrated that alterations in circulating Tfh cell subsets have significant effects on the progression of numerous autoimmune diseases. To address the role of circulating Tfh cells in psoriasis, we used flow cytometry to analyse frequencies of circulating Tfh cell subsets and levels of IL-21 receptor (IL-21R) expression on B cells in 32 patients with psoriasis vulgaris and 13 sex- and age-matched healthy controls. We observed dynamic changes in Tfh17 cell frequency and disease severity in 10 psoriasis patients during a 6-month treatment. Our results demonstrate that the frequency of Tfh17 cells was significantly increased in psoriasis patients and was positively correlated with psoriasis area and severity index (PASI) score, a marker of disease severity (P<0.05). During the follow-up period, the frequencies of Tfh17 cells decreased, and reductions in PASI scores were observed. Moreover, IL-21R expression on B cells was significantly increased in patients with psoriasis vulgaris (P<0.05). Interestingly, IL-21R levels on B cells were correlated with both PASI score and the frequency of Tfh17 cells (P<0.05). In conclusion, this study is the first investigation of the distribution of circulating Tfh subsets in psoriasis. These results deepen our understanding of the immune state of psoriasis patients. Our data also indicate that Tfh17 cells may not be good biomarkers for diagnosing psoriasis but may be potential biomarkers of disease severity in psoriasis.

Primary biliary cirrhosis-associated hepatocellular carcinoma in Chinese patients: incidence and risk factors.

AIM: To investigate the incidence, characteristics, and risk factors for hepatocellular carcinoma (HCC) in Chinese patients with primary biliary cirrhosis (PBC). METHODS: We reviewed the data of 52 PBC-associated HCC patients treated at Beijing 302 Hospital from January 2002 to December 2013 and analyzed its incidence and characteristics between the two genders. The risk factors for PBC-associated HCC were analyzed via a case-control study comprising 20 PBC patients with HCC and 77 matched controls without HCC. The matched factors included gender, age, follow-up period and Child-Pugh scores. Conditional logistic regression was used to evaluate the odds ratios of potential risk factors for HCC development. A P < 0.05 was considered statistically significant. RESULTS: The incidence of HCC in Chinese PBC patients was 4.13% (52/1255) and was significantly higher in the males (9.52%) than in the females (3.31%). Among the 52 PBC patients with HCC, 55.76% (29/52) were diagnosed with HCC and PBC simultaneously, and 5.76% (3/52) were diagnosed with HCC before PBC. The males with PBC-associated HCC were more likely than the females to have undergone blood transfusion (18.75% vs 8.33%, P = 0.043), consumed alcohol (31.25% vs 8.33%, P = 0.010), smoked (31.25% vs 8.33%, P = 0.010), had a family history of malignancy (25% vs 5.56%, P = 0.012), and had serious liver inflammation, as indicated by the elevated levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase (P < 0.05). Conditional logistic regression analysis revealed that body mass index (BMI) ≥ 25 [adjusted odds ratio (AOR) = 1.116, 95%CI: 1.002-1.244, P = 0.045] and history of alcohol intake (AOR = 10.294, 95%CI: 1.108-95.680, P = 0.040) were significantly associated with increased odds of HCC development in PBC patients. CONCLUSION: HCC is not rare in Chinese PBC patients. Risk factors for PBC-associated HCC include BMI ≥ 25 and a history of alcohol intake. In addition to regular monitoring, PBC patients may benefit from abstinence from alcohol and body weight control.

The ratio of circulating regulatory T cells (Tregs)/Th17 cells is associated with acute allograft rejection in liver transplantation.

CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) and Th17 cells are known to be involved in the alloreactive responses in organ transplantation, but little is known about the relationship between Tregs and Th17 cells in the context of liver alloresponse. Here, we investigated whether the circulating Tregs/Th17 ratio is associated with acute allograft rejection in liver transplantation. In present study, thirty-eight patients who received liver transplant were enrolled. The patients were divided into two groups: acute allograft rejection group (Gr-AR) (n = 16) and stable allograft liver function group (Gr-SF) (n = 22). The frequencies of circulating Tregs and circulating Th17 cells, as well as Tregs/Th17 ratio were determined using flow cytometry. The association between Tregs/Th17 ratio and acute allograft rejection was then analyzed. Our results showed that the frequency of circulating Tregs was significantly decreased, whereas the frequency of circulating Th17 cells was significantly increased in liver allograft recipients who developed acute rejection. Tregs/Th17 ratio had a negative correlation with liver damage indices and the score of rejection activity index (RAI) after liver transplantation. In addition, the percentages of CTLA-4(+), HLA-DR(+), Ki67(+), and IL-10(+) Tregs were higher in Gr-SF group than in Gr-AR group. Our results suggested that the ratio of circulating Tregs/Th17 cells is associated with acute allograft rejection, thus the ratio may serve as an alternative marker for the diagnosis of acute rejection.

Synchronization of stochastic competitive neural networks with different timescales and reaction-diffusion terms.

We propose a feedback controller for the synchronization of stochastic competitive neural networks with different timescales and reaction-diffusion terms. By constructing a proper Lyapunov-Krasovskii functional, as well as employing stochastic analysis theory, the LaShall-type invariance principle for stochastic differential delay equations, and a linear matrix inequality (LMI) technique, a feedback controller is designed to achieve the asymptotical synchronization of coupled stochastic competitive neural networks. A simulation example is given to show the effectiveness of the theoretical results.

Enantioselective synthesis of planar chiral ferrocenes via palladium-catalyzed annulation with diarylethynes.

When Boc-L-Val-OH was used as a ligand for the enantioselective Pd(II)-catalyzed annulation of N,N-substituted aminomethyl ferrocene derivatives with diarylethynes, ferrocenes with planar chirality could be achieved with excellent enantioselectivity (up to 99% ee).

Enantioselective synthesis of planar chiral ferrocenes via palladium-catalyzed direct coupling with arylboronic acids.

Enantioselective Pd(II)-catalyzed direct coupling of aminomethylferrocene derivatives with boronic acids was realized. With commercially available Boc-L-Val-OH as a ligand, planar-chiral ferrocenes could be synthesized in yields of 14-81% with up to 99% ee under mild conditions.

Energy exchange between two noncollinear filament-forming laser pulses in air.

Energy exchange between two filament-forming pulses with initially free chirp in air was experimentally studied. It occurs because of the change of delayed nonlinear refractive index, which slightly chirps the incident filament-forming laser pulses. Accompanying energy exchange process, spectral characteristics of output laser pulses shows dramatic blueshift and supercontinuum generation. Nonlinear absorptive effect introduces an inbalance between energy exchange at the negative delays and that at the positive delays, and affects the energy exchange efficiency. These results may provide a more comprehensive understanding of energy exchange process between filament-forming laser pulses.