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Lithium-rich layered cathode oxides attract enormous attention due to their superior capacity, high voltage and environmentally friendliness. However, it is considerable that they suffer from serious capacity fade, voltage attenuation and phase transition deriving from inevitable oxygen evolution. In this work, polyanions are induced on the surface of the oxides via the method of surface substitution, considering synergy effects of bulk substitution and surface modification to stabilize crystal structure and promote electrochemical properties. The material doped with 5 wt% PO43− exhibits excellent specific capacity of 217.1 mAh g−1 with capacity retention of 88.43% and average discharge voltage drop of 0.4846 V after 200 cycles at 0.5 C significantly superior to the pristine material. And the discharge capacity of the material can reach 105.6 mAh g−1 at 10 C owing to enlarged interlayer spacing and improved ionic conductivity. Transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and electrochemical impedance spectroscopy (EIS) of the material before and after cycle verify that polyanions are beneficial to supply more active oxygen, restrain transition metal migration, reduce surface microstrain, and enhance electronic and ionic conductivities. All above indicate that it is effective for polyanions to promote lithium-rich cathode oxides to give full play to their electrochemical advantages.

ObjectiveIgG4-related disease (IgG4-RD) is a heterogeneous, multiorgan condition of unclear aetiology that can cause organ failure. Difficulty recognising IgG4-RD contributes to diagnostic delays. We sought to identify key IgG4-RD phenotypes.MethodsWe used two cross-sectional studies assembled by an international, multispecialty network of IgG4-RD specialists who submitted 765 cases to derive and replicate phenotypic groups. Phenotype groups of disease manifestations and key covariate distributions across the identified groups were measured using latent class analysis.ResultsIn the derivation cohort (n=493), we identified four groups with distinct manifestations: Group 1 (31%), Pancreato-Hepato-Biliary disease; Group 2 (24%), Retroperitoneal Fibrosis and/or Aortitis; Group 3 (24%), Head and Neck-Limited disease and Group 4 (22%), classic Mikulicz syndrome with systemic involvement. We replicated the identification of four phenotype groups in the replication cohort. Compared with cases in Groups 1, 2 and 4, respectively, cases in Group 3 were more likely to be female (OR 11.60 (95% CI 5.39 to 24.98), 10.35 (95% CI 4.63 to 23.15) and 9.24 (95% CI 3.53 to 24.20)) and Asian (OR 6.68 (95% CI 2.82 to 15.79), 7.43 (95% CI 2.97 to 18.56) and 6.27 (95% CI 2.27 to 17.29)). Cases in Group 4 had a higher median serum IgG4 concentration (1170 mg/dL) compared with groups 1–3 (316, 178 and 445 mg/dL, respectively, pConclusionWe identified four distinctive IgG4-RD phenotypes according to organ involvement. Being Asian or female may predispose individuals to head and neck-limited disease. These phenotypes serve as a framework for identifying IgG4-RD and studying its aetiology and optimal treatment.

ObjectivesRheumatoid arthritis (RA)-specific anti-citrullinated protein/peptide antibodies (ACPAs) might contribute to bone loss and arthralgia before the onset of joint inflammation. We aimed to dissect additional mechanisms by which ACPAs might contribute to development of joint pathology.MethodsFibroblast-like synoviocytes (FLS) were isolated from the synovial membrane of patients with RA. The FLS cultures were stimulated with polyclonal ACPAs (anti-CCP-2 antibodies) purified from the peripheral blood of patients with RA or with monoclonal ACPAs derived from single synovial fluid B cells. We analysed how ACPAs modulate FLS by measuring cell adhesion and mobility as well as cytokine production. Expression of protein arginine deiminase (PAD) enzymes and protein citrullination were analysed by immunofluorescence, and signal transduction was studied using immunoblotting.ResultsChallenge of FLS by starvation-induced stress or by exposure to the chemokine interleukin-8 was essential to sensitise the cells to ACPAs. These challenges led to an increased PAD expression and protein citrullination and an ACPA-mediated induction of FLS migration through a mechanism involving phosphoinositide 3-kinase activation. Inhibition of the PAD enzymes or competition with soluble citrullinated proteins or peptides completely abolished the ACPA-induced FLS migration. Different monoclonal ACPAs triggered distinct cellular effects in either fibroblasts or osteoclasts, suggesting unique roles for individual ACPA clones in disease pathogenesis.ConclusionWe propose that transient synovial insults in the presence of a certain pre-existing ACPA repertoire might result in an ACPA-mediated increase of FLS migration.

Oxidative stress aggravates brain injury following ischemia/reperfusion (I/R). We previously showed that ubiquilin-1 (Ubqln1), a ubiquitin-like protein, improves proteostasis and protects brains against oxidative stress and I/R induced brain injury. Here, we demonstrate that a small molecule compound, L-2-oxothiazolidine-4-carboxylic acid (OTC) that functions as a precursor of cysteine, upregulated Ubqln1 and protected cells against oxygen glucose deprivation-induced cell death in neuronal cultures. Further, the administration of OTC either at 1 hour prior to ischemia or 3 hours after the reperfusion significantly reduced brain infarct injury and improved behavioral outcomes in a stroke model. Administration of OTC also increased glutathione (GSH) level and decreased superoxide production, oxidized protein, and neuroinflammation levels in the penumbral cortex after I/R in the stroke mice. Furthermore, I/R reduced both Ubqln1 and the glutathione S-transferase protein levels, whereas OTC treatment restored both protein levels, which was associated with reduced ubiquitin-conjugated protein level. Interestingly, in the Ubqln1 knockout (KO) mice, OTC treatment showed reduced neuroprotection and increased ubiquitin-conjugated protein level when compared to the similarly treated non-KO mice following I/R, suggesting that OTC-medicated neuroprotection is, at least partially, Ubqln1-dependent. Thus, OTC is a potential therapeutic agent for stroke and possibly for other neurological disorders and its neuroprotection involves enhanced proteostasis.

Catalyst supports are known to play important role in governing overall catalyst activity and durability. Here, a new type of SnO2–TiO2 solid solution (TixSn1-xO2) support was prepared via a solvothermal method with substitution of Ti4+ by Sn4+ in the TiO2 lattice. Furthermore, the TixSn1-xO2 was combined with conventional carbon black (Vulcan XC-72) to prepare a hybrid support (TixSn1-xO2–C) for depositing Pt nanoparticles. The ratios of Sn vs. Ti in the solid-solution and TixSn1-xO2 vs. XC-72 were systematically optimized in terms of their performance as supports for methanol oxidation. Compared to Pt/TiO2–C and commercial Pt/C catalysts, the best performing Pt/Ti0.9Sn0.1O2–C catalyst exhibited the highest activity, evidenced by methanol oxidation and CO stripping experiments. The well-dispersed Pt nanoparticles (2–3 nm) are mostly deposited on the boundaries of Ti0.9Sn0.1O2 and carbon blacks. Formation of the special triple junction structure can play an important role in improving Pt utilization with increased electrochemical active surface areas (ESA) of Pt. In addition, the enhanced activity for Pt supported on Ti0.9Sn0.1O2–C is due to high content of OH group on Ti0.9Sn0.1O2 along with the strengthened metal-supports interactions. Both promote the oxidation of poisoning CO absorbed on Pt active sites.

Objectives/Hypothesis To further recognize the comorbid diseases of immunoglobulin G4-related sialadenitis (IgG4-RS) in the head and neck region and to observe the response of these conditions to immunomodulatory therapy. Study Design Retrospective review. Methods The symptoms of comorbid diseases and medical histories in 51 patients (24 men, 27 women; median age, 55 years) diagnosed with IgG4-RS were analyzed. Thirty-six patients received immunomodulatory therapy and were followed up for 10.4 ± 5.9 months. Computed tomography (CT) examination was performed before and after therapy. Results Rhinosinusitis occurred in 58.8% patients, and manifested with the symptoms of nasal obstruction, nasal xerosis, and hyposmia. In addition, 43.1% patients had allergic rhinitis. Lymphadenopathy was identified in 74.5% patients. Lacrimal gland swelling occurred in 78.4% patients. Extraocular muscles, otologic organs, skin and superficial soft tissue, and cranial nerves were also involved. All of the lesions were relieved after immunomodulatory therapy. The Lund-Mackay scores decreased (9.6 ± 5.6 to 1.0 ± 2.2) according to CT analyses (P

Background Immunoglobulin G4-related sialadenitis (IgG4-RS) is a newly recognized immune-mediated systemic disease. Despite its good response to steroid therapy, its treatment protocol is not standardized and the long-term outcome is controversial. The study was conducted to determine the short-term and long-term outcomes of IgG4-RS patients treated with glucocorticoids and steroid-sparing immunosuppressive agents, to analyze secretory function, serological and radiological changes in salivary glands and to assess the usefulness of serum IgG4 level as an indicator of disease activity. Methods IgG4-RS patients who were treated for more than 3 months were enrolled. Serological tests, salivary gland function assessment and computed tomography (CT) were performed before treatment and during follow up. The treatment outcomes in the short and the long term were evaluated, and the relationship between serum IgG4 level and salivary gland volume was analyzed. Results Glucocorticoids were used in all 43 patients and steroid-sparing immunosuppressive agents in 38 patients (88.4%). The follow-up period was 24.6 ± 14.9 months. Clinical remission was achieved in all patients after induction therapy. During short-term observation, salivary gland secretion significantly increased, and the serum IgG4 levels, the volumes and CT values of submandibular and parotid gland decreased significantly (P

The time-convolutionless (TCL) quantum master equation provides a powerful tool to simulate reduced dynamics of a quantum system coupled to a bath. The key quantity in the TCL master equation is the so-called kernel or generator, which describes effects of the bath degrees of freedom. Since the exact TCL generators are usually hard to calculate analytically, most applications of the TCL generalized master equation have relied on approximate generators using second and fourth order perturbative expansions. By using the hierarchical equation of motion (HEOM) and extended HEOM methods, we present a new approach to calculate the exact TCL generator and its high order perturbative expansions. The new approach is applied to the spin-boson model with different sets of parameters, to investigate the convergence of the high order expansions of the TCL generator. We also discuss circumstances where the exact TCL generator becomes singular for the spin-boson model, and a model of excitation energy transfer in the Fenna-Matthews-Olson complex.

Tan-67 is a selective non-peptidic δ-opioid receptor (DOR) agonist that confers neuroprotection against cerebral ischemia/reperfusion (I/R)-caused neuronal injury in pre-treated animals. In this study, we examined whether post-ischemic administration of Tan-67 in stroke mice is also neuroprotective and whether the treatment affects expression, maturation and processing of the amyloid precursor protein (APP). A focal cerebral I/R model in mice was induced by middle cerebral artery occlusion for 1 hour (h) and Tan-67 ( 1.5, 3 or 4.5 mg/kg) was administered via the tail vein at 1 h after reperfusion. Alternatively, naltrindole, a selective DOR antagonist (5 mg/kg), was administered 1 h before Tan-67 treatment. Our results showed that post-ischemic administration of Tan-67 (3 mg/kg or 4.5 mg/kg) was neuroprotective as shown by decreased infarct volume and neuronal loss following I/R. Importantly, Tan-67 improved animal survival and neurobehavioral outcomes. Conversely, naltrindole abolished Tan-67 neuroprotection in infarct volume. Tan-67 treatment also increased APP expression, maturation and processing in the ipsilateral penumbral area at 6 h but decreased APP expression and maturation in the same brain area at 24 h after I/R. Tan-67-induced increase of APP expression was also seen in the ischemic cortex at 24 h following I/R. Moreover, Tan-67 attenuated BACE-1 expression, β-secretase activity and the BACE cleavage of APP in the ischemic cortex at 24 h after I/R, which was abolished by naltrindole. Our data suggest that Tan-67 is a promising DOR-dependent therapeutic agent for treating I/R-caused disorder and that Tan-67-mediated neuroprotection may be mediated via modulating APP expression, maturation and processing, despite an uncertain causative relationship between the altered APP and the outcomes observed.

We aimed to characterize the molecular differences and effects from prednisone treatment among IgG4-related disease with salivary gland lesions (RD-SG), without SG lesions (RD-nonSG), and IgG4-related retroperitoneal fibrosis (RF). RNA sequencing was conducted on blood from 25 RD-SG, 11 RD-nonSG, 3 RF and 10 control subjects. Among these, 8 RD-nonSG and 12 RD-SG patients were subjected to treatment with prednisone and/or glucocorticoid-sparing agents. Six RD patients had a longitudinal time point. The mRNA levels of IgG4 and IgE, genes specific for Th2 cells, eosinophils, and neutrophils were over-expressed in RD-SG and RD-nonSG. A B-cell signature was suppressed in patients group versus controls, while Th1, Th2, Treg, and eosinophil gene signatures were increased in patients without treatment. Interestingly, Tfh genes and B cell signature were decreased at flare disease state. Prednisone treatment led to increased neutrophil, but decreased Treg signatures. Serum IgG4 levels correlated with the eosinophil and neutrophil gene signatures in RD-SG patients, and with a B cell signature in only RD-nonSG patients. IgG4, IgE, and cell-specific signatures are regulated in patients, suggesting the imbalance of immune and inflammatory cells in IgG4-related disease. Prednisone treatment selectively modulates Treg, eosinophil, and neutrophil signatures.

Lithium-rich layered oxides (LLOs) have been attractive cathode materials for lithium-ion batteries because of their high reversible capacity. However, they suffer from low initial Coulombic efficiency and capacity/voltage decay upon cycling. Herein, facile surface modification of Li

Alzheimer’s disease (AD), characterized by the accumulation of β-amyloid (Aβ) plaques and tau neurofibrillary tangles in the brain, neuroinflammation and neurodegeneration, is the most common form of neurodegenerative disease among the elderly. No effective treatment is available now in restricting the pathological progression of AD. The aim of this study is to determine the therapeutic efficacy of stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) (SCF+G-CSF) in aged APPswe/PS1dE9 (APP/PS1) mice. SCF+G-CSF was subcutaneously injected for 12 days to 25-month-old male APP/PS1 mice. We observed that SCF+G-CSF treatment reduced the Aβ plaques in both the cortex and hippocampus. SCF+G-CSF treatment increased the association of TREM2+/Iba1+ cells with Aβ plaques and enhanced Aβ uptake by Iba1+ and CD68+cells in the brains of aged APP/PS1 mice. Importantly, cerebral expression area of P2RY12+and TMEM119+ homeostatic microglia and the branches of P2RY12+ homeostatic microglia were increased in the SCF+G-CSF-treated aged APP/PS1 mice. SCF+G-CSF treatment also decreased NOS-2 and increased IL-4 in the brains of aged APP/PS1 mice. Moreover, the loss of MAP2+dendrites and PSD-95+post-synapses and the accumulation of aggregated tau in the brains of aged APP/PS1 mice were ameliorated by SCF+G-CSF treatment. Furthermore, the density of P2RY12+ microglia was negatively correlated with Aβ deposits, but positively correlated with the densities of MAP2+ dendrites and PSD-95+ puncta in the brains of aged APP/PS1 mice. These findings reveal the therapeutic potential of SCF+G-CSF treatment in ameliorating AD pathology at the late stage.

Lithium-rich layered cathode material Li1·2Ni0·13Co0·13Mn0·54O2 has attracted extensive attention owing to high specific capacity and energy density from its distinctive anionic redox chemistry. However, the material suffers from low Coulombic efficiency, serious capacity attenuation, severe voltage decay which can be ascribed to the irreversible oxygen loss and phase transformation. Herein, oxygen defects are induced through the pre-extraction of lithium and oxygen from Li2MnO3 component on the surface of the material accompanying with the generation of spinel structure via a facile method of hydrothermal reaction assisted with calcination clarified by X-ray photoelectron spectroscopy (XPS) and high-resolution transmission electron microscopy (HRTEM). The material exhibits excellent electrochemical properties including enhanced initial Coulombic efficiency over 87% and prominent capacity retention of 89.7% after 100 cycles superior to those for the pristine, which are attributed to the fact that oxygen defects inhibit evolution of oxygen, and alleviate the lattice microstrain along consecutive delithiation/lithiation process to improve mechanical property of material. Besides, the Galvanostatic Intermittent Titration Technique (GITT) manifests that the material possesses superior dynamic condition. These results indicate that oxygen defects are beneficial to stabilize the lattice oxygen on the surface of the lithium-rich layered oxides for a high-performance cathode material for lithium-ion batteries.

There has been a long history of applying the generalized master equation (GME) to study charge carrier and exciton transport in molecular systems. Yet exact memory kernels in the GME are generally difficult to obtain. In this work, exact memory kernels of the Nakajima-Zwanzig-Mori GME for a one dimensional Holstein type of model are calculated by employing the Dyson relation for the exact memory kernel, combined with the hierarchical equations of motion method. Characteristics of the exact memory kernels, as well as the transition rate constants within the Markovian approximation, are then analyzed for different sets of parameters ranging from the hopping to bandlike transport regimes. It is shown that, despite the memory effect of the exact kernels, the Markovian approximation to the exact GME can reproduce the diffusion constants accurately. We also investigate the validity of the second and fourth order perturbation theories with respect to the electronic coupling constant in calculating the rate constants and the diffusion constant. It is found that, due to the cancellation of errors, the second order diffusion constant gives a reasonable estimate of the exact one within a wide range of electronic coupling constants.

Ubiquilin-1 (Ubqln1 or Ubqln), a ubiquitin-like protein, mediates degradation of misfolded proteins and has been implicated in a number of pathological and physiological conditions. To better understand its functionin vivo, we recently generated transgenic (Tg) mice that globally overexpress mouse Ubqln in a variety of tissues andubqlnconditional knock-out mice. The Tg mice were viable and did not show any developmental or behavioral abnormalities compared with their wild-type (WT) littermates. When subjected to oxidative stress or ischemia/reperfusion, however,ubqlnTg mice but not the WT littermates showed increased tolerance to these insults. Following ischemic stroke,ubqlnTg mice recovered motor function more rapidly than did the WT mice. In contrast, KO ofubqlnexacerbated neuronal damage after stroke. In addition, KO ofubqlnalso caused accumulation of ubiquitinated proteins. WhenubqlnKO mice were crossed with a ubiquitin-proteasome system function reporter mouse, the accumulation of a proteasome surrogate substrate was observed. These results suggest that Ubqln protects mice from oxidative stress and ischemic stroke-caused neuronal injury through facilitating removal of damaged proteins. Thus, enhanced removal of unwanted proteins is a potential therapeutic strategy for treating stroke-caused neuronal injury.

Acute hepatitis C virus (HCV) infection is primarily followed by chronic infection, while spontaneous recovery of HCV infection (SR-HCV) occurs in a minority of those infected. Identification of SR-HCV clinically depends on two combined indicators, persistently undetectable peripheral HCV RNA and positivity for anti-HCV. However, the characteristics of dynamic variation in anti-HCV antibodies in SR-HCV, especially in those patients co-infected with HIV, are still undefined. In this study, a cohort of patients infected with HCV through commercial blood collection practices was studied. We found that the annual decreasing rate of anti-HCV presented a gradually accelerated process in HCV resolvers. However, the variation in the decline of anti-HCV presented a slowly accelerated process within the early decrease stage and a gradually decelerated process within the latter decrease stage. In addition, we deduced that it expended approximately 16 years from natural HCV recovery to undetectable peripheral anti-HCV in HCV resolvers co-infected with HIV, while this time was estimated to be 20 years in SR-HCV without HIV co-infection. Our data indicated that the decay of anti-HCV was accelerated by HIV-related impairment of immune function. The prevalence of HCV infection may be severely underestimated in this large-scale retrospective epidemiologic investigation in an HIV-infected population.

Alzheimer's disease (AD), the most common cause of dementia, is neuropathologically characterized by accumulation of insoluble fibrous inclusions in the brain in the form of intracellular neurofibrillary tangles and extracellular senile plaques. Perturbation of the ubiquitin-proteasome system (UPS) has long been considered an attractive hypothesis to explain the pathogenesis of AD. However, studies on UPS functionality with various methods and AD models have achieved non-conclusive results. To get further insight into UPS functionality in AD, we have crossed a well-documented APPswe/PS1dE9 AD mouse model with a UPS functionality reporter, GFPu, mouse expressing green fluorescence protein (GFP) fused to a constitutive degradation signal (CL-1) that facilitates its rapid turnover in conditions of a normal UPS. Our western blot results indicate that GFPu reporter protein was accumulated in the cortex and hippocampus, but not striatum in the APPswe/PS1dE9 AD mouse model at 4 weeks of age, which is confirmed by fluorescence microscopy and elevated levels of p53, an endogenous UPS substrate. In accordance with this, the levels of ubiquitinated proteins were elevated in the AD mouse model. These results suggest that UPS is either impaired or functionally insufficient in specific brain regions in the APPswe/PS1dE9 AD mouse model at a very young age, long before senile plaque formation and the onset of memory loss. These observations may shed new light on the pathogenesis of AD.

La(Fe, Si)13-based compounds are well-known magnetocaloric materials, which show a pronounced negative thermal expansion (NTE) around the Curie temperature but have not been considered as NTE materials for industrial applications. The NaZn13-type LaFe13-xSix and LaFe11.5-xCoxSi1.5 compounds were synthesized, and their linear NTE properties were investigated. By optimizing the chemical composition, the sharp volume change in La(Fe, Si)13-based compounds was successfully modified into continuous expansion. By increasing the amount of Co dopant in LaFe11.5-xCoxSi1.5, the NTE shifts toward a higher temperature region, and also the NTE operation-temperature window becomes broader. Typically, the linear NTE coefficient identified in the LaFe10.5Co1.0Si1.5 compound reaches as much as -26.1 × 10(-6) K(-1), with an operation-temperature window of 110 K from 240 to 350 K, which includes room temperature. Such control of the specific composition and the NTE properties of La(Fe, Si)13-based compounds suggests their potential application as NTE materials.

A new type of Ce-doped α-MoO

Our aim was to differentiate IgG4-related sialadenitis, primary Sjogren syndrome, and chronic obstructive submandibular sialadenitis by analysing clinical, radiographic, and pathological features. Fifty-five patients, 50, and 50 were enrolled, respectively and their baseline characteristics and serological, sialographic, and pathological findings compared. The male:female ratio for IgG4-related sialadenitis was 1:1.2 for primary Sjogren syndrome 1:15.7, and for chronic obstructive submandibular sialadenitis1:0.92. Numbers with enlarged salivary glands were 55, 16, and 50; with xerostomia 26, 48, and 0; with a history of allergy 26, 4, and 6, and with coexisting systemic disease 12, 19, and 0 (p=0.14). Mean (SD) serum IgG4 concentrations were 109.1 (97.9), 4.9. (1.9) g/L, and 5.3 (1.6) g/L, p

Objective To investigate the inhibitory effect and possible mechanism of a novel influenza virus hemagglutinin 308–317 peptide (altered HA308–317 peptide) in collagen-induced arthritis (CIA). Methods CIA was induced in DBA/1 mice by immunization with type II collagen (CII). Altered HA308–317 peptide, wild HA308–317 peptide, wild CII263–272 peptide, and irrelevant peptide were administered intranasally beginning at arthritis onset. Clinical and histologic scores were assessed, and cytokine levels were determined in the serum or in supernatants from splenocytes. Characteristics of T cell subsets in response to different peptides were analyzed both in vivo and in vitro. Results Intranasal administration of wild CII263–272 peptide, wild HA308–317 peptide, or altered HA308–317 peptide could significantly ameliorate CIA, but altered HA308–317 peptide showed greater therapeutic effects than wild CII263–272 peptide and wild HA308–317 peptide. The effect of altered HA308–317 peptide was associated with a substantial decrease in production of interleukin-17 (IL-17) and interferon-γ (IFNγ) and with a marked increase in production of IL-10 and transforming growth factor β, both in serum and in supernatants from splenocytes treated with altered HA308–317 peptide. Both the number and function of CD4+ Treg cells were significantly up-regulated by altered HA308–317 peptide, with a decreased induction of Th1 cells (CD4+IFNγ+) and Th17 cells (CD4+IL-17+). Adoptive transfer of CD4+CD25+ T cells from altered HA308–317 peptide–treated mice resulted in greater suppressive capacity in ameliorating CIA severity than did adoptive transfer of CD4+CD25+ T cells from wild HA308–317 peptide–treated, wild CII263–272 peptide–treated, or irrelevant peptide–treated mice. Conclusion Intranasal administration of altered HA308–317 peptide potently suppressed the severity of CIA by increasing the number and function of CD4+ Treg cells, suggesting that altered HA308–317 peptide might be a promising candidate for treatment of rheumatoid arthritis.

Although previous studies have demonstrated the involvement of nitrated alpha-synuclein in neurodegenerative disorders (synucleinopathies), the effects of nitrated alpha-synuclein and the molecular mechanisms underlying its toxicity are still unclear. In the present study, nitrated alpha-synuclein with four 3-nitrotyrosines (Tyr(39), Tyr(125), Tyr(133), and Tyr(136)) was obtained non-enzymatically by incubation with nitrite. The nitrated protein existed as a mixture of monomers, dimers, and polymers in solution. The nitrated alpha-synuclein could induce cell death in a time-and concentration-dependent manner when SH-SY5Y cells (a human neuroblastoma cell line) were incubated with the dimers and polymers. Treatment with anti-integrin alpha 5 beta 1 antibody partially rescued the SH-SY5Y cells from the cell death. Dot blotting and immunoprecipitation revealed that the nitrated protein bound to integrin on the cell membranes. Level of nitric oxide (NO) and calcium-independent inducible NO synthase (iNOS) activity increased during the initial stages of the treatment. The expression of phosphorylated focal adhesion kinase (FAK) decreased in the cells. Subsequently, an increase in caspase 3 activity was observed in SH-SY5Y cells. Our results demonstrate that activation of iNOS and inhibition of FAK may both be responsible for the cell death induced by nitrated alpha-synuclein. These data suggest that the cytotoxicity of nitrated alpha-synuclein is mediated via an integrin-iNOS/-FAK signaling pathway, and that the nitration of alpha-synuclein plays a role in neuronal degeneration.

A rapid, sensitive and accurate high performance liquid chromatography method using tandem mass spectrometry detection for hydralazine in BALB/C mouse plasma and brain was developed and validated. The method involved a derivatization with 2,4-pentanedione at 50 °C for 1 h, and a step of solid phase extraction to purify and concentrate hydralazine derivative. Chromatographic separation was carried out on an Agilent ZORBAX SB-C18 column by elution with methanol–0.01 mol L−1 ammonium acetate (60:40, v/v). The multiple reaction monitoring transition used for quantification was m/z 225.2 → 129.5 in the electrospray positive ionization mode. Good linearity was obtained over the concentration range of 10–200 ng mL−1. The limits of detection were 0.49 and 1.05 ng mL−1 for hydralazine in mouse plasma and brain, respectively. The limits of quantitation were 1.5 and 3.18 ng mL−1 for hydralazine in mouse plasma and brain, respectively. Sample analysis time was 6 min including sample separation. The method was successfully applied to a pharmacokinetic study following intraperitoneal injection of hydralazine in BALB/C mice at the dose of 20 mg kg−1.

Objective.To explore the potential role of Dickkopf-1 (DKK-1) in rheumatoid arthritis (RA) and to evaluate the effect of a tumor necrosis factor-α (TNF-α) inhibitor (infliximab) and an interleukin 1 receptor antagonist (IL-1Ra; anakinra) on DKK-1 secretion in patients with RA.Methods.Serum samples were collected from 100 patients with RA, 100 patients with other rheumatic diseases (e.g., osteoarthritis and ankylosing spondylitis), and 40 healthy controls. DKK-1 and osteoprotegerin (OPG) levels in serum were detected by ELISA. Serum C-reactive protein (CRP) levels, erythrocyte sedimentation rates (ESR), rheumatoid factor (RF) titers, and anti-cyclic citrullinated peptide antibody were also measured in patients with RA.Results.The serum level of DKK-1 was significantly higher in patients with RA than in healthy controls and those with other rheumatic diseases (p < 0.01); the serum DKK-1 level was correlated with levels of CRP (r = 0.488, p = 0.003) and ESR (r = 0.458, p = 2.4 x 10−4) and the Sharp score of radiologic change (r = 0.449, p = 0.001) in RA. In contrast to the increasing level of OPG, DKK-1 was significantly decreased in RA patients treated with TNF-α inhibitor (p < 0.01). DKK-1 was significantly decreased in RA patients treated with IL-1Ra (p < 0.01).Conclusion.DKK-1, as an important mediator, was correlated with bone erosion and inflammation in RA. The change of DKK-1 level may serve as a biomarker of disease activity and bone erosion.

We propose a non-perturbative method to simulate heterogeneous electron transfer dynamics in systems described by a Newns-Anderson type of model. The coupling between the molecule and the continuum electronic states at the metal or semiconductor surface is represented using a set of effective modes, by employing an exponential expansion of the bath correlation functions. Depending on the nature of the problems, the nuclear degrees of freedom are either treated explicitly using wave functions and density operators or as dissipative modes using the techniques from the hierarchical equations of the motion method. Numerical examples are also presented for applications in problems including (1) photo-induced charge transfer at the molecule-semiconductor interfaces, (2) heterogeneous electron transfer at the molecule-metal interface, and (3) vibrational relaxation on a metal surface.

Although the relationship between hyperglycemia (using diabetic animal model) and plasma nitrotyrosine level has been studied, the effect of hypoglycemia on nitrotyrosine level in the brain has not been addressed. Here, we evaluated nitration of protein, the colocalization of nitration with alpha-synuclein, activity of inducible nitric oxide synthase, and nitric oxide content using fasting and diabetic animal models. The results showed that signals of alpha-synuclein were widely distributed in most parts of the pallium, midbrain, hippocampus and cerebellum, as indicated by immunohistochemistry. Most signals of the 3-nitrotyrosine were colocalized with those of alpha-synuclein in the midbrain of fasting rats. The level of proteins containing 3-nitrotyrosine was significantly increased in the brain of fasting rats in Western blotting, especially in the midbrain, compared with control rats. In addition, the 3-nitrotyrosine signals increased in hippocampus of diabetic rats. Immunoprecipitation showed that alpha-synuclein was nitrated in the fasting rats. The iNOS activity and nitric oxide levels were significantly increased in both fasting and diabetic animals. The enhanced 3-nitrotyrosine level in the brain of fasting rats suggests that nitration of protein including alpha-synuclein in the midbrain is more affected by hypoglycemia in fasting than hyperglycemia in diabetic rats. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Stroke is a serious medical condition that causes long-term neurological disability in mainly elderly adults worldwide. Lack of therapy to improve functional recovery in the chronic phase of stroke is a major challenge for stroke research. Combining two hematopoietic growth factors, stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF), our previous studies have demonstrated the neurovascular restorative efficacy of this treatment in the chronic phase of experimental stroke. Elevated plasma fibrinogen has been thought to serve as a predictor for ischemic stroke. Here we have determined the treatment frequency in reducing plasma fibrinogen and in restoring motor function in aged mice with chronic stroke. Our findings show that SCF + G-CSF treatment in chronic stroke decreases plasma fibrinogen and improves motor function in aged mice. No differences have been found between a 2-week treatment regimen and 7-day treatment in the plasma fibrinogen assay, while the 7-day treatment regimen displays a better recovery pattern with regard to motor function. This study provides new insight into understanding the potential contribution of SCF + G-CSF in both reducing the risk of recurrent ischemic stroke and enhancing stroke recovery.

Aim The objective of this study was to identify proteomic biomarkers specific for rheumatoid arthritis (RA) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in combination with weak cationic exchange (WCX) magnetic beads. Methods Serum samples from 50 patients with RA and 110 disease controls (50 SLE and 60 SS) and 51 healthy individuals were analyzed. The samples were randomly divided into a training set or test set to develop a diagnostic model for RA. Results A total of 83 protein peaks were identified to be related with RA, in which four of the peaks with mass-charge ratio (m/z) at 8133.85, 5844.60, 13 541.3 and 14 029.0 were selected to establish a model for diagnosis of RA. This classification model could separate patients with RA from diseased and healthy controls with sensitivity of 84.0% and specificity of 92.5%, and its accuracy was confirmed in the blind testing set with high sensitivity and specificity of 80.0% and 93.3%, respectively. Conclusions This study suggested that potential serum biomarkers for RA diagnosis could be discovered by MALDI-TOF-MS. The classification tree model set up in this study might be used as a novel diagnostic tool for RA.

Introduction Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition. Forty-two cases with immunoglobulin G4-related sialadenitis (IgG4-RS) confirmed by histopathological and immunohistochemical assessment were studied to clarify the clinicopathologic characteristics of the salivary glands involved in IgG4-RS, especially the relationship between the histopathologic features and function of salivary glands or serum levels of IgG4. Methods Clinical, serologic, imaging and histopathological data of these cases were analyzed. CT volumes of submandibular, parotid, and lacrimal glands were calculated. The saliva flow rate was measured. Scintigraphy with 99mTc-pertechnetate was undertaken in 31 cases, and the concentration index (CI) and secretion index (SI) was calculated. Relationships between fibrosis severity and salivary gland function or serum IgG4 levels were analyzed. Results The first symptom was swelling of bilateral submandibular or lacrimal glands. Physical examination showed multiple bilateral major salivary glands (including sublingual and accessory parotid glands) and lacrimal glands were enlarged in IgG4 RS. Multiple enlarged cervical lymph nodes were noted in 30 patients. Saliva flow at rest was lower than normal in 34 cases; stimulated saliva flow was lower than normal in 15 cases. Secretory function was reduced more severely in the submandibular glands than in the parotid glands. Serum levels of IgG4 were elevated in 95.2% of cases and 78.6% patients had increased IgE levels. Serum IgG4 level was higher and saliva secretion lower as glandular fibrosis increased. Conclusions Prominent changes in the morphology, histology, immunohistochemistry and secretion of the major salivary glands of IgG4-RS patients were accompanied by involvement of the lacrimal glands and cervical lymph nodes. Elevated IgE, allergic history, eosinophil infiltration suggest allergic reactions as a potential pathogenesis of IgG4-RS. Severity of glandular fibrosis correlated with salivary function and serum levels of IgG4.

To summarize the clinical features and laboratory data of 77 patients with hemophagocytic syndrome (HPS).A total of 77 patients of HPS were continuously collected from 2007 to 2014 at our hospital. Their underlying diseases, clinical features, laboratory data, therapy and prognosis were analyzed.Their The patients aged from 3 months to 85 years. The gender ratio was roughly equal. Primary HPS was diagnosed in only 5 cases by gene detection Another 72 cases belonged to secondary HPS. The causes were infection (n = 28), hematologic neoplasm (n = 25), autoimmune diseases (AID, n = 11) and unknown (n = 8). HPS was the initial symptom in nearly half cases of hematologic neoplasm and AID. HPS was characterized by high fever (100%), hypersplenomegaly (81.8%) and lymphadenopathy (40.3%). Laboratory data showed cytopenia (94.8%), serum ferritin elevation (93.2%), hypofibrinogenemia (61.8%), hemophagocytosis in bone marrow (78.1%) and hypertriglyceridemia (55.3%). Low NK-cell activity (95.2%) and elevation of sCD25 (100%) were specific manifestations in HPS. Pulmonary infection (36.4%) and hepatic malfunction (33.3%) were common. Approximately 70% were treated with HLH-2004. Pulse-dose corticosteroid therapy (methylprdnisolone 200-500 mg/d) was used in 8 AID patients. And 14 patients died and 10 withdrew treatment because of exacerbation. Five had complications of DIC and another 5 progressed into MODS. Neoplasm (52.0%) had the highest mortality in secondary HPS. And infection (25.0%) and AID (18.2%) followed.Sometimes HPS occurs simultaneously with autoimmune disease or neoplasm. Relevant laboratory tests for suspected patients may aid an early diagnosis. Presence of DIC or MODS in HPS is possibly correlated with a poor prognosis and a high mortality.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common condition of hereditary stroke and vascular dementia. CADASIL is caused by Notch3 mutation, leading to progressive degeneration of vascular smooth muscle cells (vSMCs) of the small arteries in the brain. However, the pathogenesis of CADASIL remains largely unknown, and treatment that can stop or delay the progression of CADASIL is not yet available. Using both wild type mice and transgenic mice carrying the human mutant Notch3 gene (CADASIL mice), we have recently characterized the pathological features of CADASIL and determined the therapeutic efficacy of two hematopoietic growth factors, stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) in CADASIL. Our findings have revealed novel pathological changes in the endothelium of cerebral capillaries and in the neural stem cells (NSCs). We have also observed the impairment of cognitive function in CADASIL mice. Moreover, SCF+G-CSF treatment improves cognitive function, inhibits Notch3 mutation-induced vSMC degeneration, cerebral blood bed reduction, cerebral capillary damage, and NSC loss, and increases neurogenesis and angiogenesis. Here we compile an overview of our recently published studies, which provide new insights into understanding the pathogenesis of CADASIL and developing therapeutic strategies for this devastating neurological disease.

Graphite Oxide Cathode for Greener Rechargeable Aluminum Battery In recent years, with the gradual depletion of traditional energy, Secondary battery is being widely researched and applied, and will become a vital force in a plenty variety of new green energy. Aluminium is the most abundant metal in the earth’s crust and each aluminum ion carries three electrons which make the capacity of the aluminum ion battery is expected to be greatly improved. Additionally, aluminum ion battery might offer significant cost savings and safety improvements over the Li-ion battery platform due to the price of aluminum is much lower than that of lithium. However, at present, the working voltage and energy density of the aluminum ion battery is lower than that of the lithium ion battery, so it is urgent to develop a new kind of positive electrode material of aluminum ion battery to improve the electrochemical performance. [1-2] In the work, we report on a novel Al-ion battery system using graphite oxide as the cathode against an aluminium metal anode in an ionic liquid (IL), 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([BMIM]OTF) and aluminum trifluoromethanesulfonate (Al(OTF)3), -based electrolyte. [3] As shown in Figure 1a, the charge and discharge capacity gradually decreased with the increase of cycle number. However, reduction of discharge capacity is much smaller than that of the charge capacity. As shown in Figure 1b, with the increase of cycle number, the discharge capacity is gradually reduced and the coulombic efficiency is gradually increased, which are consistent with the results obtained from the Fig.1a. It can be seen from the Fig.1a that the first discharge capacity of graphite oxide cathode is only 26.7 mAh/g and its electrochemical polarization is relatively large, so we will further improve the oxidation graphite to enhance the electrochemical properties of aluminum ion batteries. Reference 1. Dunn, B.; Kamath, H.; Tarascon, J.M., (2011) Electrical energy storage for the grid: a battery of choices. Science, 334: 928-935 2. Lin, M.C.; Gong, M.; Lu, B.; Wu, Y. P.; Wang, D.Y.; Guan, M.; Angell, M.; Chen, C.;Yang, J.; Hwang, B.J.; Dai, H., (2015) An Ultrafast Rechargeable Aluminium-Ion Battery. Nature, 520: 524-528. 3. wang, H.L.; Gu, S.C.; Bai, Y.; Chen, S.; Wu, F.; Wu, C.; (2016) A high-voltage and non-corrosive ionic liquid electrolyte used in rechargeable aluminum battery. ACS Appl. Mater. Interfaces, 8: 27444-27448. Acknowledgments The experimental research was funded by the National Natural Science Foundation of China (no.51572024, 51372021) Figure 1

Autoimmune hemolytic anemia (AIHA) is an uncommon but clinically significant disorder in primary Sjogren’s syndrome (pSS). Among 565 pSS patients hospitalized in Peking University People’s Hospital from January 2000 to March 2013, 16 patients were diagnosed with AIHA (2.8 % prevalence). AIHA presented at the onset of pSS without overt sicca symptoms in 3 of the 16 patients. Primary biliary cirrhosis (PBC) was more prevalent in the patients with SS-AIHA than in those without (p = 0.007). Edema, fever, and liver involvement occurred significantly more frequently in pSS patients with AIHA than those without AIHA (p = 0.035, p = 0.029, p = 0.024, respectively). The pSS patients with AIHA were more vulnerable to leukopenia and thrombocytopenia than those without AIHA (p = 0.004 and p = 0.001, respectively). Additionally, the levels of complement component 3 (C3) and complement component 4 (C4) were significantly lower in the SS-AIHA group (p = 0.008 and p = 0.037, respectively). Taken together, our results indicate that pSS should be considered in the differential diagnosis of AIHA, even in the absence of sicca symptoms. Among pSS patients, the existence of PBC, cytopenia, or hypocomplementemia suggests a higher risk of suffering from AIHA.

Primary Sjogren’s syndrome (pSS) is a systemic autoimmune disease that lacks sensitive and specific diagnostic methods. The aim of this study was to identify potential biomarkers specific for pSS and to establish a diagnostic model. Serum samples from patients with pSS, disease controls (DC, patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA)), and healthy controls (HC)) were randomly divided into a training set (35 pSS, 50 DC, and 26 HC) and a testing set (25 pSS, 50 DC, and 25 HC). Weak cationic exchange (WCX) magnetic beads were used to differentially capture serum proteins prior to proteomic analysis. Proteomic mass spectra were generated by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). One hundred differential M/Z peaks associated with pSS were identified, and the m/z peaks at 8,133.85, 11,972.8, 2,220.81, and 4,837.66 were used to establish a diagnostic model for pSS. This diagnostic model was able to distinguish pSS from non-pSS controls with a sensitivity of 77.1 % and a specificity of 85.5 %, and its efficacy was confirmed in our blinded testing set with good sensitivity and specificity of 95.5 and 88 %, respectively. The results indicated that the proteomic fingerprinting model was effective in the diagnosis of pSS.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a Notch3 dominant mutation-induced cerebral small vascular disease, is characterized by progressive degeneration of vascular smooth muscle cells (vSMCs) of small arteries in the brain, leading to recurrent ischemic stroke, vascular dementia and death. To date, no treatment can stop or delay the progression of this disease. Herein, we determined the therapeutic effects of stem cell factor (SCF) in combination with granulocyte colony-stimulating factor (G-CSF) (SCF + G-CSF) in a mouse model of CADASIL carrying the human mutant Notch3 gene. SCF + G-CSF was subcutaneously administered for 5 days and repeated 4 times with 1–4 month intervals. We found through water maze testing that SCF + G-CSF treatment improved cognitive function. SCF + G-CSF also attenuated vSMC degeneration in small arteries, increased cerebral blood vascular density, and inhibited apoptosis in CADASIL mice. We also discovered that loss of cerebral capillary endothelial cells and neural stem cells/neural progenitor cells (NSCs/NPCs) occurred in CADASIL mice. SCF + G-CSF treatment inhibited the CADASIL-induced cell loss in the endothelia and NSCs/NPCs and promoted neurogenesis. In an in vitro model of apoptosis, SCF + G-CSF prevented apoptotic cell death in vSMCs through AKT signaling and by inhibiting caspase-3 activity. These data suggest that SCF + G-CSF restricts the pathological progression of CADASIL. This study offers new insights into developing therapeutic strategies for CADASIL.

Mycorrhizas play key roles in important ecosystem processes and functions. To enhance our understanding of the impact of mycorrhizal strategies on important foliar traits of host plants and their response to climate changes, we analysed 6 selected foliar traits among 54 plant species in 129 sampling sites of ascertained mycorrhizal types on the Tibetan Plateau based on their functional groups. The selected traits were leaf mass per area (LMA), nitrogen concentration (on mass and area bases, Nmass and Narea, respectively), photosynthetic capacity (Amass and Aarea) and photosynthetic nitrogen use efficiency (PNUE). The analysed foliar traits showed no significant difference between arbuscular mycorrhizas (AM) and non-mycorrhizas (NM) + AM in the grass group. Mycorrhizal strategies remarkably affected Nmass and Amass of the herb group, and LMA, Amass and Nmass in the shrub group. Responses of foliar traits to precipitation and temperature varied among different mycorrhizal strategies. The index of LMA, Aarea and Narea of AM, Narea of NM/AM, and PNUE of mean annual precipitation (MAP) were significantly affected by mean annual temperature (MAT). The responses among different mycorrhizal types to precipitation and temperature differed among plant functional groups.

Recent advances in trans-differentiation of one type cell to another have made it possible to directly convert Huntington's disease (HD) patient fibroblasts into neurons by modulation of cell-lineage-specific transcription factors or RNA processing. However, this possibility has not been examined. Here, we demonstrate that HD patient-derived fibroblasts can be directly trans-differentiated into neuron-like cells by knockdown of the expression of a single gene encoding the polypyrimidine-tract-binding protein. The directly converted HD neuron-like cells were positive in expression of Tuj1, NeuN, DARPP-32, and γ-aminobutyric acid and exhibited neuritic breakdown, abnormal neuritic branching, increased cell death, and aggregation of mutant huntingtin. These observations indicate that the neuron-like cells directly converted from HD patient fibroblasts recapitulate the major aspects of neuropathological characteristics of HD and thus provide an additional model for understanding the disorder and validation of therapeutic reagents.

The ubiquitin proteasome system (UPS) is impaired in Huntington's disease, a devastating neurodegenerative disorder. Sulforaphane, a naturally occurring compound, has been shown to stimulate UPS activity in cell cultures. To test whether sulforaphane enhances UPS function in vivo, we treated UPS function reporter mice ubiquitously expressing the green fluorescence protein (GFP) fused to a constitutive degradation signal that promotes its rapid degradation in the conditions of a healthy UPS. The modified GFP is termed GFP UPS reporter (GFPu). We found that both GFPu and ubiquitinated protein levels were significantly reduced and the three peptidase activities of the proteasome were increased in the brain and peripheral tissues of the mice. Interestingly, sulforaphane treatment also enhanced autophagy activity in the brain and the liver. To further examine whether sulforaphane promotes mutant huntingtin (mHtt) degradation, we treated Huntington's disease cells with sulforaphane and found that sulforaphane not only enhanced mHtt degradation but also reduced mHtt cytotoxicity. Sulforaphane-mediated mHtt degradation was mainly through the UPS pathway as the presence of a proteasome inhibitor abolished this effect. Taken together, these data indicate that sulforaphane activates protein degradation machineries in both the brain and peripheral tissues and may be a therapeutic reagent for Huntington's disease and other intractable disorders. Accumulation of mutant huntingtin (mHtt) protein causes Huntington's disease (HD). Sulforaphane (SFN), a naturally occurring compound, increased proteasome and autophagy activities in vivo and enhanced mHtt turnover and cell survival in HD cell models. SFN-mediated mHtt degradation is mainly through the proteasome pathway. These data suggest that SFN can be a therapeutic reagent for treating HD and other intractable disorders.

Accurate and timely extraction of snow cover information is of great significance in the monitoring and assessment of snow disasters. However, remote sensing observations in snowing weathers were susceptible to the impacts of clouds and atmospheric water vapor, consequently snow parameters mapping from remote sensing data usually became difficult. This study presents an integrated approach for snow cover mapping by combining the two MODIS acquisitions and passive microwave sensor data collected in a day. For purposes of validation, the daily Terra and Aqua MODIS surface reflectance and AMSR-E brightness temperature data of January, 2010 were used in snow cover mapping and snow depth estimation in Xinjiang, China. Comparison between the results using the proposed approach and the observational data acquired in the metrological stations of Xinjiang indicates that the accuracy of the retrieval of snow parameters is 80.5%, and can combine the advantages of both optical and microwave remote sensors. Afterwards, the proposed approach was used to extract the snow covers and depth information in a typical heavy snow process in Xinjiang from Nov. 30 to Dec. 18, 2012. A simple assessment model was built based on the retrievals and used to evaluate the disaster situation. Field check in the north Xinjiang in January, 2013 showed that the results could be used in the early evaluation of the snow disaster management.

Due to usual higher oil and gas production, high permeable reservoirs are considered to be forgiving and to be able to hold up very well against formation damage induced by any solids and liquids, so these reservoirs have not deserved a fair share of that attention. In fact, any formation damage can inevitably alter the permeability of the porous media and adversely affect oil recovery to different degrees, and the damage is more deadly to horizontal well. Triassic reservoir with the maximum permeability of more than 2 Darcy and the maximum throat sizes of more than 100 μm in the Tarim Basin provides us with a perfect example. Horizontal well is the key technique to increase oil production in this reservoir. However, after completion, horizontal wells can not produce through natural power or gas-lift, and did not present the advantages of increasing production compared with vertical wells. The results of granularity analysis and dynamic damage evaluation experiments present that the original drill-in fluids can not protect the reservoir with permeability of more than 100 mD, while the percentage of regain permeability is less than 50%. The drilling fluids were modified by adding fibrous bridging agents instead of common spherical bridging agents to rapidly form a tight plugging zone near the wellbore that efficiently seals the large pore throats. The dynamic filtration test and the analysis of mudcake through the FEI Quanta 450 environment scanning electron microscope (ESEM) showed that the optimized drill-in fluids can form tight filter cakes, plug the pore of reservoir effectively, and enhance the percentage of regain permeability of core samples up to 90%. After the application of the new drill-in fluids, horizontal wells are in high flowing production after completion, and the wellbore quality are also improved.

There has been an increase in interest in the use of altered peptides as antigen-specific therapeutic agents in autoimmune diseases. Here we investigated the inhibitory effect and possible mechanism of an altered influenza virus haemagglutinin (HA)-derived peptide in collagen-induced arthritis (CIA). CIA was induced in DBA/1 mice by immunisation with type II collagen (CII). Altered HA308-317, wild-type HA308-317 or irrelevant peptide was administered intranasally beginning from arthritis onset. Clinical and histological scores were assessed, and cytokine levels in the serum or supernatants from splenocytes were determined. The percentages of Th1 and Th2 cells in response to different peptides were analysed by FACS both in vivo and in vitro. Our results showed that intranasal administration of altered HA308-317 peptide significantly ameliorated CIA. The therapeutic effect of altered HA308-317 peptide was associated with a substantial decrease in production of interferon (IFN)-γ, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, anti-CII IgG, IgG1 and IgG2a antibodies, and an markedly increase in production of IL-10 and IL-4 in serum or supernatants from splenocytes treated with altered HA308-317 peptide. The percentage of Th2 (CD4(+)IL-4(+)) cells was upregulated significantly by altered HA308-317 peptide with a decreased percentage of Th1 (T helper 1; CD4(+)INF-γ(+)) cells both in vivo and in vitro. These findings suggest that altered HA308-317 peptide might be a promising candidate for rheumatoid arthritis (RA) treatment.

A microwave drying system with the ability of automatic temperature and power control was developed for molybdenum drying. The samples' mass and the moisture content could be obtained online. Four different drying modes were attempted with different combination of temperature and power controls. Feedback temperature control with predefined variable power profiles resulted in the best temperature control and product quality. All other modes proved their own pros and cons. The study also verified that it was difficult to maintain a constant temperature during microwave drying process when a feedback temperature control was not included. The results can be used to determine microwave power levels in microwave drying practices both with and without temperature control.

Objective. SS is an autoimmune disease characterized by salivary and lacrimal gland dysfunction leading to dry mouth (xerostomia) and dry eyes (xerophthalmia). Anti-muscarinic acetylcholine type-3 receptor (anti-M3R) autoantibodies have been shown to be a good serum marker in primary SS (pSS). The aim of this study was to assess the clinical correlations of anti-M3R-derived peptide antibodies in patients with pSS. Methods. Sequences of the first to fourth cycle-M3R (c1 M3R-c4M3R)-derived peptide was synthesized by a solid-phase technique on an Applied Biosytems Peptide Synthesizer. Synthesized cM3R peptide (cM3RP) was used as substrate in an ELISA to detect IgG anti-cM3RP antibodies in serum samples of patients and controls. The clinical and biological parameters of the diseases were also evaluated. The EULAR SS disease activity index (ESSDAI) score was used to measure disease activity in patients with primary SS. Results. (i) Anti-c2M3RP antibodies were highly prevalent in pSS patients, and the titre is much higher than anti-c1,3,4M3RP antibodies. (ii) The prevalence of anti-c2M3RP antibodies in pSS, SLE, RA and healthy controls was 62.2, 7.1, 5.3 and 1.6%, respectively. The prevalence of anti-linear-2-M3RP antibodies in pSS, SLE and RA patients and healthy controls were 56.1, 20.0, 14.7 and 9.4%. (iii) The specificity of anti-c2M3RP antibodies was 95.1 %, much higher than that of linear polypeptide (84.7%) for pSS diagnosis. (iv) In pSS patients, anti-c2M3RP positivity had significantly increased frequency in patients who were RF or ANA positive, and had several haematological abnormalities, such as leucopenia, anaemia and thrombocytopenia. Furthermore, the ESSDAI score was significantly higher in anti-c2M3RP-positive pSS patients (P < 0.05). Conclusion. Anti-c2M3RP antibody was highly specific for patients with pSS. The presence of anti-c2M3RP antibody in pSS indicates that c2M3RP may act as an autoantigen that may play a role in the pathogenesis of pSS.

This paper describes a novel image registration method that combines log-polar transform and SIFT to recover similarity transformations (rotation/ scale/ translation). We extracts SIFT feature points in the two images firstly. Then, we use threshold Euclidean distance to coarsely match the feature points. After that, the log-polar transform is applied to compute the rotation and scale parameters. And we can obtain the translation parameter by the location relationship of the feature points.