Punch‑excised explants of bovine mammary gland to model early immune response to infection

Background Mammary gland(MG)infections(mastitis)are frequent diseases of dairy cows that affect milk quality,animal welfare and farming profitability.These infections are commonly associated with the bacteria Escherichia coli and Staphylococcus aureus.Different in vitro models have been used to investigate the early response of the MG to bacteria,but the role of the teat in mastitis pathogenesis has received less attention.In this study,we used punch-excised teat tissue as an ex vivo model to study the immune mechanisms that arise early during infection when bacteria have entered the MG.Results Cytotoxicity and microscopic analyses showed that bovine teat sinus explants have their morphology and viability preserved after 24 h of culture and respond to ex vivo stimulation with TLR-agonists and bacteria.LPS and E.coli trigger stronger inflammatory response in teat when compared to LTA and S.aureus,leading to a higher produc-tion of IL-6 and IL-8,as well as to an up-regulation of proinflammatory genes.We also demonstrated that our ex vivo model can be applied to frozen-stored explants.Conclusions In compliance with the 3Rs principle(replacement,reduction and refinement)in animal experimenta-tion,ex vivo explant analyses proved to be a simple and affordable approach to study MG immune response to infec-tion.This model,which better reproduces organ complexity than epithelial cell cultures or tissue slices,lends itself particularly well to studying the early phases of the MG immune response to infection.

Multi-Compartment SCFA Quantification in Human

Short-chain fatty acids (SCFA) play an important role in human biochemistry. They originate primarily from the digestive system through carbohydrates microbial fermentation. Most SCFA produced in the colon are absorbed by the intestinal wall and enter the bloodstream to be distributed throughout the body for multiple purposes. At the intestinal level, SCFA play a role in controlling fat storage and fatty acid metabolism. The effects of these beneficial compounds therefore concern overall health. They facilitate energy expenditure and are valuable allies in the fight against obesity and diabetes. SCFA are also involved in the regulation of the levels of several neurotransmitters such as GABA (γ-aminobutyric acid), glutamate, serotonin, dopamine, and norepinephrine. Their role is also highlighted in many inflammatory and neurodegenerative diseases such as Alzheimer’s disease (AD) or Parkinson’s disease (PD). To have a realistic picture of the distribution of SCFA in different biological compartments of the human body, we propose to study SCFA simultaneously in five human biological samples: feces, saliva, serum, cerebrospinal fluid (CSF), and urine, as well as in Dried Blood Spot (DBS). To evaluate their concentration and repeatability, we used 10 aliquots from pooled samples, analyzed by 3-nitrophenylhydrazine (3-NPH) derivation and liquid chromatography coupled with high sensitivity mass spectrometry (LC-QqQ-MS). We also evaluated the SCFA assay on Dried Blood Spot (DBS). In this work, we adapted the pre-analytical parts for each sample to be able to use a common calibration curve, thus facilitating multi-assay quantification studies and so being less time-consuming. Moreover, we proposed new daughter ions from the same neutral loss (43 Da) to quantify SCFAs, thus improving the sensitivity. In conclusion, our methodology, based on a unique calibration curve for all samples for each SCFA, is well-suited to quantified them in a clinical context.

Therapeutic potential of α7 nicotinic receptor agonists to regulate neuroinflammation in neurodegenerative diseases

Neurodegenerative diseases, such as Alzheimer＇s, Parkinson＇s and Huntington＇s diseases, are all character- ized by a component of innate immunity called neuroinflammation. Neuronal loss and neuroinflammation are two phenomena closely linked. Hence, the neuroinflammation is a relevant target for the management of the neurodegenerative diseases given that, to date, there is no treatment to stop neuronal loss. Several studies have investigated the potential effects of activators of alpha 7 nicotinic acetylcholine receptors in animal models of neurodegenerative diseases. These receptors are widely distributed in the central nervous system. After activation, they seem to mediate the cholinergic anti-inflammatory pathway in the brain. This anti-inflammatory pathway, first described in periphery, regulates activation of microglial cells considered as the resident macrophage population of the central nervous system. In this article, we shortly review the agonists of the alpha 7 nicotinic acetylcholine receptors that have been evaluated in vivo and we focused on the selective positive allosteric modulators of these receptors. These compounds represent a key element to enhance receptor activity only in the presence of the endogenous agonist.

Alpha-7 nicotinic acetylcholine receptor agonist treatment in a rat model of Huntington's disease and involvement of heme oxygenase-1

Neuroinflammation is a common element involved in the pathophysiology of neurodegenerative diseases.We recently reported that repeated alpha-7 nicotinic acetylcholine receptor（α7 n ACh R） activations by a potent agonist such as PHA 543613 in quinolinic acid-injured rats exhibited protective effects on neurons.To further investigate the underlying mechanism,we established rat models of early-stage Huntington＇s disease by injection of quinolinic acid into the right striatum and then intraperitoneally injected 12 mg/kg PHA 543613 or sterile water,twice a day during 4 days.Western blot assay results showed that the expression of heme oxygenase-1（HO-1）,the key component of the cholinergic anti-inflammatory pathway,in the right striatum of rat models of Huntington＇s disease subjected to intraperitoneal injection of PHA 543613 for 4 days was significantly increased compared to the control rats receiving intraperitoneal injection of sterile water,and that the increase in HO-1 expression was independent of change in α7 n ACh R expression.These findings suggest that HO-1 expression is unrelated to α7 n ACh R density and the increase in HO-1 expression likely contributes to α7 n ACh R activation-related neuroprotective effect in early-stage Huntington＇s disease.

Effect of cation(Li^+, Na^+, K^+, Rb^+, Cs^+) in aqueous electrolyte on the electrochemical redox of Prussian blue analogue(PBA) cathodes

Prussian blue analogue(PBA)material is a promising cathode for applications in Na-ion and K-ion batteries which can support high c-rates for charge and discharge.In this study,the material of composition[K2 CuIIFeII(CN)6]was synthesized and its structural and electrochemical redox behavior was investigated with 5 different alkali insertion cations(Li^+,Na^+,K^+,Rb^+,Cs^+).Galvanostatic measurements indicate that the redox potential strongly depends on the ionic radius of the inserted cation.The redox potential varies by 400 m V between using Li^+(0.79A)or Cs^+(1.73A)in the electrolyte.The underlying modification of the Fe2^+/Fe3^+redox potential in PBA is proposed to be due to the weakening of the Fe–C bond in the material.This hypothesis is supported by XRD measurements which reveal that the lattice parameter of the de-intercalated host structure follows the same trend of monotonic increase with the cation size.The relatively minor volume changes accompanying the redox(1.2%–2.4%)allow the PBA to accommodate differently sized cations,although the structural hindrances are quite pronounced at high c-rates for the larger ones(Rb^+and Cs^+).Cycle aging studies indicate that the minimum capacity fade rate is observed in case of K^+ and Rb^+ containing electrolyte.The peak intensity corresponding to the[220]crystallographic plane varies depending on the state of charge of PBA,since this plane contains the insertion cations.Owing to the sensitivity of the redox potential to the insertion cation coupled with the observed fast ion-exchange ability,the PBA material may find additional analytical applications such as ion sensing or filtration devices.

Protic ionic liquids/poly(vinylidene fluoride) composite membranes for fuel cell application

Poly(vinylidene fluoride), PVDF, membranes have attracted considerable attention as polymer electrolytes for fuel cells. This study explores the effect of solvent on the spherulite size and the crystallinity of the polymeric membranes. Based on Hansen solubility parameters theory, the mixture of DMC and DMSO was selected among a dozen of solvents for the preparation of PVDF membranes by thermally induced phase separation. The addition of two protic ionic liquids(PILs), bis(2-ethyl hexyl) ammonium hydrogen phosphate [EHNH_2][H_2PO_4], and imidazolium hexanoate [Im][Hex] to PVDF membranes at concentrations(10% < wP IL< 50%) has been investigated by SEM, FTIR, DSC, TGA, EIS, and DMA. The inclusion of ionic liquids into the polymer matrix influences structural parameters(degree of crystallinity and electroactive phases), thermal stability, proton conductivity and mechanical properties of the membranes. The membranes become transparent regardless type of ionic liquid employed. A small amount of ionic liquids increases the degree of crystallinity and facilitates the production of polar β and γ crystals. The proton conductivity mechanism(Grotthuss) is dependent on the ionic liquid structure(due to its selforganization in water) and the content in the PVDF membrane, as well as the membrane water uptake.Different behavior has been observed for the two ionic liquids, which stresses the challenge on selecting an appropriate cation and anion combination. The obtained composite membranes exhibited excellent mechanical performance and reduced elastic modulus, with respect to the pure polymer matrix. These results indicate that PVDF/IL composite membranes have a high potential for PEMFC applications.

Neuroprotective and anti-inflammatory effects of a therapy combining agonists of nicotinic α7 and σ1 receptors in a rat model of Parkinson’s disease

To date there is no treatment able to stop or slow down the loss of dopaminergic neurons that characterizes Parkinson’s disease.It was recently observed in a rodent model of Alzheimer’s disease that the interaction between the α7 subtype of nicotinic acetylcholine receptor(α7-nAChR)and sigma-1 receptor(σ1-R)could exert neuroprotective effects through the modulation of neuroinflammation which is one of the key components of the pathophysiology of Parkinson’s disease.In this context,the aim of the present study was to assess the effects of the concomitant administration of N-(3R)-1-azabicyclo[2.2.2]oct-3-yl-furo[2,3-c]pyridine-5-carboxamide(PHA)543613 as an α7-nAChR agonist and 2-(4-morpholinethyl)1-phenylcyclohexanecarboxylate(PRE)-084 as aσ1-R agonist in a well-characterized 6-hydroxydopamine rat model of Parkinson’s disease.The animals received either vehicle separately or the dual therapy PHA/PRE once a day until day 14 postlesion.Although no effect was noticed in the amphetamine-induced rotation test,our data has shown that the PHA/PRE treatment induced partial protection of the dopaminergic neurons(15-20%),assessed by the dopamine transporter density in the striatum and immunoreactive tyrosine hydroxylase in the substantia nigra.Furthermore,this dual therapy reduced the degree of glial activation consecutive to the 6-hydroxydopamine lesion,i.e,the 18 kDa translocation protein density and glial fibrillary acidic protein staining in the striatum,and the CD11b and glial fibrillary acidic protein staining in the substantia nigra.Hence,this study reports for the first time that concomitant activation of α7-nAChR andσ1-R can provide a partial recovery of the nigro-striatal dopaminergic neurons through the modulation of microglial activation.The study was approved by the Regional Ethics Committee(CEEA Val de Loire n°19)validated this protocol(Authorization N°00434.02)on May 15,2014.

Transit time ultrasound perivascular flow probe technology is superior to MR imaging on hepatic blood flow measurement in a porcine model

Background: The hepatic hemodynamics is an essential parameter in surgical planning as well as in various disease processes. The transit time ultrasound(TTUS) perivascular flow probe technology is widely used in clinical practice to evaluate the hepatic inflow, yet invasive. The phase-contrast-MRI(PC-MRI) is not invasive and potentially applicable in assessing the hepatic blood flow. In the present study, we compared the hepatic inflow rates using the PC-MRI and the TTUS probe, and evaluated their predictive value of post-hepatectomy adverse events. Methods: Eighteen large white pigs were anaesthetized for PC-MRI and approximately 75% hepatic resection was performed under a unified protocol. The blood flow was measured in the hepatic artery(Qha), the portal vein(Qpv), and the aorta above the celiac trunk(Qca) using PC-MRI, and was compared to the TTUS probe. The Bland-Altman method was conducted and a partial least squares regression(PLS) model was implemented. Results: The mean Qpv measured in PC-MRI was 0.55 ± 0.12 L/min, and in the TTUS probe was 0.74 ± 0.17 L/min. Qca was 1.40 ± 0.47 L/min in the PC-MRI and 2.00 ± 0.60 L/min in the TTUS probe. Qha was 0.17 ± 0.10 L/min in the PC-MRI, and 0.13 ± 0.06 L/min in the TTUS probe. The Bland-Altman method revealed that the estimated bias of Qca in the PC-MRI was 32%(95% CI:-49% to 15%); Qha 17%(95% CI:-15% to 51%); and Qpv 40%(95% CI:-62% to 18%). The TTUS probe had a higher weight in predicting adverse outcomes after 75% resection compared to the PC-MRI( β= 0.35 and 0.43 vs β = 0.22 and 0.07, for tissue changes and premature death, respectively). Conclusions: There is a tendency of the PC-MRI to underestimate the flow measured by the TTUS probes. The TTUS probe measures are more predictive of relevant post-hepatectomy outcomes.

Small dissymmetry, yet large effects on the transport propertiesof electrolytes based on imide salts: Consequences on performancein Li-ion batteries

To gain better insight into the influence of the anion size and symmetry on the transport properties and thermal stability of an electrolyte based on lithium(fluorosulfonyl)(trifluoromethanesulfonyl)-imide(FTFSI)salt,we performed the physical and electrochemical characterization of an electrolyte based on FTFSI incorporated in standard binary(3 EC/7 EMC)and ternary(EC/PC/3 DMC)alkylcarbonate mixtures.By applying the Jones-Dole-Kaminsky(JDK),Eyring and Arrhenius empirical models to the electrolyte viscosity we show that the activation enthalpy and entropy energy barriers(ΔH≠,ΔS≠)for viscous flow are between 12 and 15 kJ·mol^(-1).They are strongly dependent on the solvent nature and are significantly lower than their symmetric anions LiFSI and LiTFSI(19-20 kJ·mol^(-1))in the binary mixture.Furthermore,the hydrodynamic radius,rs,calculated by JDK,and the ionicity behavior illustrated by the Walden role,showed that the FTFSI anion is outside the solvation sphere(rs>0.6 nm)which is smaller in the case of an EC/EMC solvent base.In the 3 EC/7 EMC solvent mixture,LiFTFSI is less conductive than in the ternary mixture i.e.,σ_(max)=8.9 mS cm^(-1) at C_(max)=1.1 mol L^(-1) for 3 EC/7 EMC and,σ_(max)=10.5 mS cm^(-1) at max=0.7 mol L^(-1) for EC/PC/3 DMC,due to a strong solvation and a greater association of FTFSI ions in the binary solvent mixture.The thermal stability of FTFSI based electrolytes was determined by the shift of the evaporation temperature of the volatile solvents(DMC,EMC)in the presence of salt,towards the higher temperatures.This feature is visible on the thermograms obtained by DSC both with the liquid electrolyte and with charged LMO cathodes in presence of electrolytes.The consequences of these properties on the electrochemical behavior of a graphite(Gr)half-cell,a lithium metal(Li)anode and a manganese lithium oxide(LMO)cathode demonstrated on the one hand the formation of a thick solid electrolyte interphase(SEI)on graphite that consumed a significant amount of lithium i.e.,18%of total capacity of the first charge.Furthermore,LiFTFSI delivered 95%of the initial capacity C=360 mAh g^(-1) at C/10 with EC/PC/3 DMC versus 91%when it was combined with 3 EC/7 EMC C=348 mAh g^(-1),while the capacities obtained for LiTFSI in EC/PC/3 DMC were the lowest(C=275 mAh g^(-1))compared to those of the other salts.After 10 cycles,the capacity loss at C/20 is<2%for LiFSI and LiFTFSI with the two solvent mixtures.On the other hand,manganese dissolution from LMO as well as current collector corrosion were confirmed by post-mortem examination of opened coin cells.The incompatibility of the LMO cathode with an electrolyte based on FTFSI was confirmed by the position of the decomposition peak of charged LMO in contact with this electrolyte observed by DSC These results demonstrate that the nature of the anion as well as the composition of the solvent considerably influence the performance of imide-based lithium salts both on the anode,but especially on the high voltage cathode.

Initial Geometry and Strike-Slip Deformation of Skarn Related Iron Deposit: Insights from Paleomagnetic and AMS Investigations(Yamansu Deposit, Eastern Tianshan, China)

The eastern Tianshan has great economic potential with Fe-(Cu)skarn,Cu-Ni-and V-Ti othomagmatic deposits and orogenic Au lodes.In this province the timing relation between Fe-(Cu)skarn-related deposits and the deformation is poorly constrained.This study aims to give argument for the chronology between Fe-(Cu)skarn stage

Pazopanib-induced posterior reversible encephalopathy syndrome with possible syndrome of inappropriate secretion of antidiuretic hormone: an incidental or pathophysiological association?

Introduction:Pazopanib is an oral protein kinase inhibitor(PKI)that targets vascular endothelial growth factor(VEGF)receptors,fibroblastic growth factor receptors,platelet-derived growth factor receptors,and stem cell factor that inhibits VEGF-induced cellular proliferation.Pazopanib is approved for use in advanced renal cell carcinoma and subtypes of advanced soft-tissue sarcoma(Deguchi et al.,2018).Major adverse drug reactions of pazopanib include hypertension,high-grade hyponatremia and posterior reversible encephalopathy syndrome(PRES)(Berardi et al.,2016;Deguchi et al.,2018).In clinical trials,few investigations have been conducted to determine the aetiology of PKI-associated hyponatremia,the mechanism remains therefore unknown.Only rare cases of PKI-induced syndrome of inappropriate secretion of antidiuretic hormone(SIADH)(Largeau et al.,2019),and none with pazopanib,have been reported.PRES is a clinical and radiological entity where a bilateral white matter oedema,occurring predominantly in the posterior occipital and parietal lobes,is associated with several neurologic symptoms.Interestingly,a recent review suggests that SIADH could be a symptom of PRES(Largeau et al.,2019).To our knowledge,this is the first case published where pazopanib-induced PRES occurs contemporaneously with possible SIADH.

Mec1-Dependent Phosphorylation of the Scc3 Subunit of Cohesin during Mitosis in Budding Yeast

Cohesin is an evolutionary conserved complex that controls chromosome segregation during mitosis. Here we show that, in response to DNA damage, Saccharomyces cerevisiae Scc3, one of the major regulatory subunits of the Smc1-Smc3-Scc1 cohesin ring, is phosphorylated on S/T-Q residues. This event depended on the Mec1 checkpoint kinase as well as on cell cycle arrest triggered by the DNA damage checkpoint network. This phosphorylation event also took place during mitosis of an unperturbed cell cycle. The present finding that S. cerevisiae Scc3 is phosphorylated during mitosis represents a potentially important new regulatory step in cohesin’s mitotic functions.

Development of a Fast and Facile Analytical Approach to Quantify Radiometabolites in Human Plasma Samples Using Ultra High Performance Liquid Chromatography

Introduction: Conventional metabolite analyses often require manual sample preparation, generating variability of measurements. This study describes a new method to quantify radiometabolites in blood, combining ultra high performance liquid chromatography (UHPLC) and turbulent flow chromatography, an alternative fully automated process allowing analyte’s extraction. Methods: A new radiotracer for dopamine transporter imaging, namely LBT-999, was used to demonstrate the method’s robustness. Matrix effect, Turboflow column loading, linearity, specificity and precision were evaluated with in vitro samples of LBT-999 in human plasma. Radiodetector sensitivity and preliminary evaluation were respectively determined by analysis of calibrated samples of [18F]LBT-999 and blood samples from 4 healthy subjects injected with [18F]LBT-999, withdrawn at 5, 15, 30 and 45 min pi. Results: With three sequential loadings (3 × 100 μL) of the Turboflow column, mean coefficients of variation were 1%, below 2%, 2% and 30.9% for matrix effect, specificity, repeatability and intermediate precision, respectively. Correlation coefficients for linearity were superior to 0.97. Limits of detection and quantification of the radiodetector were fixed at 3 and 9 c/s. Retention times for [18F]LBT-999 and the two radiometabolites detected by radio-UHPLC were 6.5, 4.8 and 9.6 min. Forty-five min after the injection, parent fraction was still predominant with 57.8% ± 25% of the total radioactivity. Conclusions: An innovative approach, allying UHPLC and Turboflow column, was developed and its sensitivity, linearity, specificity and repeatability validated. Preliminary results of the clinical trial are in accordance with literature data, demonstrating its efficiency in radiometabolites quantification.

Evaluation of an Ultrasound-Guided Focused Ultrasound CMUT Probe for Targeted Therapy Applications

Capacitive Micromachined Ultrasonic Transducer (CMUT) technology, which has been widely studied in the field of medical imaging, possesses strong design flexibility due to its manufacturing process. Many applications could benefit from this unique feature, especially those that require different operating ultrasonic frequencies. This article reports on the characterization of the therapeutic low-frequency field provided by an ultrasound-guided focused ultrasound CMUT probe that is connected to a custom ultrasonic scanner for hyperthermia applications. The study begins by mapping the focused ultrasonic beam in the vicinity of the focal spot and a parametric analysis providing the maximum peak-to-peak (PTP) pressure delivered by the probe under different acoustic conditions. The measured maximum PTP pressure at the targeted operating frequency of 1 MHz is 3 MPa, with a maximum of 3.6 MPa at 1.25 MHz. Based on an in vitro setup found in the literature, the temperature elevation at the focal point was measured, showing results in agreement with the targeted applications (max. ΔT = 7.5°C). The article concludes with a reliability study considering the delivered pressure and the self-heating of the CMUT probe: the results show the good stability of the pressure amplitude over 1.8 × 109 cycles at a duty cycle of 40%, with a moderate internal heating of 3°C.

Individual and Environmental Risk Factors for COVID-19 Mortality in Elderly in 7 European University Hospitals

Because the elderly account for 80% of deaths from COVID-19 and they may be more vulnerable to air pollution, in this retrospective study we aimed to explore individual and environmental risk factors for COVID-19 mortality in the geriatric departments of seven European University hospitals, between February and May 2020. Long-term exposure to air pollution was estimated through annual pollutant concentrations at the residential address over the last two years. Short-term variations in air pollutants and weather parameters were also examined through a 20-day period before the confirmed PCR diagnostic of COVID-19. We found positive associations for diabetes and COVID-19 mortality (OR 2.2 CI 95%: 1.1, 4.4). Regarding environmental factors, we found no association between COVID-19 mortality and air pollutants and weather parameters;however, our study suffers from strong disparities—such as patient characteristics—between fairly polluted and less polluted cities. In order to overcome those disparities between cities, we aimed to explore the relationship between air pollution and COVID-19 mortality within each city, but even with the high-efficiency modelisation systems, differences in air pollutants were too small to estimate the effect of air pollution at the city level. Thus, this study highlights the need to improve the estimation of individual exposure to air pollution. To address this issue, solutions exist such as the increase of the number of fixed air monitors, or even better, through the use of individual markers of air pollution exposure such as urinary black carbon or passive individual samplers. Furthermore, we underline that outdoor air pollutant concentrations may not be representative of individual exposure, especially in the elderly, thus, we suggest that further studies focus on indoor air pollution. Regarding meteorological conditions, we found no association between UV, temperature, wind speed and COVID-19 mortality. We found a positive association between an increase in relative humidity (RH) and COVID-19 mortality, however, the influence of RH on COVID-19 mortality remains unclear, and additional studies are needed to confirm this potential link.

Thermal conditioning of quail embryos has transgenerational and reversible long‑term effects

Background In the current context of global warming,thermal manipulation of avian embryos has received increasing attention as a strategy to promote heat tolerance in avian species by simply increasing the egg incubation temperature.However,because of their likely epigenetic origin,thermal manipulation effects may last more than one generation with consequences for the poultry industry.In this work,a multigenerational and transgenerational analysis of thermal manipulation during embryogenesis was performed to uncover the long-term effects of such procedure.Results Thermal manipulation repeated during 4 generations had an effect on hatchability,body weight,and weight of eggs laid in Japanese quails,with some effects increasing in importance over generations.Moreover,the effects on body weight and egg weight could be transmitted transgenerationally,suggesting non-genetic inheritance mechanisms.This hypothesis is reinforced by the observed reversion of the effect on growth after five unexposed generations.Interestingly,a beneficial effect of thermal manipulation on heat tolerance was observed a few days after hatching,but this effect was not transgenerational.Conclusions Our multigenerational study showed that thermal conditioning of quail embryos has a beneficial effect on post-hatch heat tolerance hampered by transgenerational but reversible defects on growth.Assuming that no genetic variability underlies these changes,this study provides the first demonstration of epigenetic inheritance of traits induced by environmental temperature modification associated with long-term impacts in an avian species.

The sperm-interacting proteome in the bovine isthmus and ampulla during the periovulatory period

Background Spermatozoa interact with oviduct secretions before fertilization in vivo but the molecular players of this dialog and underlying dynamics remain largely unknown.Our objectives were to identify an exhaustive list of sperm-interacting proteins(SIPs)in the bovine oviduct fluid and to evaluate the impact of the oviduct anatomical region(isthmus vs.ampulla)and time relative to ovulation(pre-ovulatory vs.post-ovulatory)on SIPs number and abundance.Methods Pools of oviduct fluid(OF)from the pre-ovulatory ampulla,pre-ovulatory isthmus,post-ovulatory ampulla,and post-ovulatory isthmus in the side of ovulation were collected from the slaughterhouse.Frozen-thawed bull sperm were incubated with OF or phosphate-buffered saline(control)for 60 min at 38.5℃.After protein extraction and digestion,sperm and OF samples were analyzed by nanoLC-MS/MS and label-free protein quantification.Results A quantitative comparison between proteins identified in sperm and OF samples(2333 and 2471 proteins,respectively)allowed for the identification of 245 SIPs.The highest number(187)were found in the pre-ovulatory isthmus,i.e.,time and place of the sperm reservoir.In total,41 SIPs(17%)were differentially abundant between stages in a given region or between regions at a given stage and 76 SIPs(31%)were identified in only one region×stage condition.Functional analysis of SIPs predicted roles in cell response to stress,regulation of cell motility,fertilization,and early embryo development.Conclusion This study provides a comprehensive list of SIPs in the bovine oviduct and evidences dynamic spatiotemporal changes in sperm-oviduct interactions around ovulation time.Moreover,these data provide protein candidates to improve sperm conservation and in vitro fertilization media.

制作体模对颅内肿瘤立体定向放疗影像的质量控制

目的:制作出体模来评估颅内肿瘤立体定向放疗中所使用的计算机断层扫描(CT)和核磁共振(MRI)影像的质量,以保证放疗的精度。方法:设计和制作出一个可用于评估的体模,并且在与放疗病人影像扫描相同的条件下,将该体模分别放在CT和MRI下进行扫描,最后在Brainlab工作站将几何参数进行对比得到MRI几何失真的大小,同时也可对融合的质量进行评估。结果:制作出的体模满足设计的要求,得到的MRI的几何失真在2mm以内,而勾画靶区体积的准确性超过99%,手工融合的误差在2 mm内,都在报道过的允许的误差范围内,满足了放疗精度的要求。结论:由于病人和机器所引起的MRI几何失真,靶区体积的误差和手工融合产生的误差是不可避免的,我们必须在一定的周期内对这些误差进行评估。实践证明,本文所介绍的体模的方法将是一种简便易行的方法。

Genetic diversity of the hepatitis C virus: Impact and issues inthe antiviral therapy

The hepatitis C Virus (HCV) presents a high degree of genetic variability which is explained by the combination of a lack of proof reading by the RNA dependant RNA polymerase and a high level of viral replication. The re- sulting genetic polymorphism defines a classification in clades, genotypes, subtypes, isolates and quasispecies. This diversity is known to reflect the range of responses to Interferon therapy. The genotype is one of the pre- dictive parameters currently used to define the antiviral treatment strategy and the chance of therapeutic suc- cess. Studies have also reported the potential impact of the viral genetic polymorphism in the outcome of antivi- ral therapy in patients infected by the same HCV geno- type. Both structural and non structural genomic regions of HCV have been suggested to be involved in the Inter- feron pathway and the resistance to antiviral therapy. In this review, we first detail the viral basis of HCV diversity. Then, the HCV genetic regions that may be implicated in resistance to therapy are described, with a focus on the structural region encoded by the E2 gene and the non- structural genes NS3, NS5A and NS5B. Both mechanisms of the Interferon resistance and of the new antiviral drugs are described in this review.

A highly concentrated vanadium protic ionic liquid electrolyte for the vanadium redox flow battery

A protic ionic liquid is designed and implemented for the first time as a solvent for a high energy density vanadium redox flow battery.Despite being less conductive than standa rd aqueous electrolytes,it is thermally stable on a 100 ℃ temperature window,chemically stable for at least 60 days,equally viscous and dense with typical aqueous solvents and most importantly able to solubilize to 6 mol L^(-1) vanadium sulfate,thus increasing the VRFB energy density by a factor of 2.5.Electrochemical measurements revealed quasi-reversible redox transitions for both catholyte and anolyte at 25 ℃ while a proof-of-concept redox flow cell with the proposed electrolyte was tested for a total of 150 cycles at 25 ℃,showing an open circuit potential of 1.39 V and energy and coulombic efficiencies of 65% and 93%,respectively.What’s more,the battery can be equally cycled at 45℃ showing good thermal stability.This study underlines a new route to improve the energy-to-volume ratio of energy storage system.