Development of novel nitric oxide production inhibitors based on the 7H-pyrrolo[2,3-d]pyrimidine scaffold.

Nitric oxide (NO), the smallest signaling molecule known, can be excessively produced by overexpressed inducible nitric oxide synthase (iNOS), and eventually leads to multiple inflammatory related diseases. Thus, reducing the overexpression of NO represents as very potential anti-inflammatory strategy. In current study, a series of compounds were designed and synthesized based on the hybridization of 7H-pyrrolo[2,3-d]pyrimidine and cinnamamide fragments in order to develop novel NO production inhibitors.

Microsecond fingerprint stimulated Raman spectroscopic imaging by ultrafast tuning and spatial-spectral learning.

Label-free vibrational imaging by stimulated Raman scattering (SRS) provides unprecedented insight into real-time chemical distributions. Specifically, SRS in the fingerprint region (400-1800 cm) can resolve multiple chemicals in a complex bio-environment. However, due to the intrinsic weak Raman cross-sections and the lack of ultrafast spectral acquisition schemes with high spectral fidelity, SRS in the fingerprint region is not viable for studying living cells or large-scale tissue samples.

Autoantibodies against C5aR1, C3aR1, CXCR3, and CXCR4 are decreased in primary Sjogren's syndrome.

Background: Networks formed of numerous autoantibodies (aabs) directed against G-protein coupled receptors (GPCR) have been suggested to play important role in autoimmune disorders. In present study, we aimed to evaluate the association between anti-GPCR antibodies and primary Sjogren's syndrome (pSS) to determine the potential pathogenic factors.

Methods: By applying a cell membrane-based ELISA technique, which is capable of detecting aabs against conformational epitopes within GPCR, serum levels of fourteen GPCR were determined in well-characterized patients with pSS (n = 52) and gender-matched healthy controls (n = 54).

Jitter-free, dual-wavelength, ultrashort-pulse, energetic fiber sources using soliton self-mode conversion.

We demonstrate an energetic dual-wavelength ultrashort pulsed source by exploiting the inherent features of the newly discovered process of soliton self-mode conversion (SSMC) in a multimode fiber. The generated pulses are at wavelengths of 1205 nm and 1273 nm, respectively, and the pulse energies are approximately 30 nJ. The natural group-velocity-locking feature of SSMC ensures minimal relative timing jitter, hence highlighting the utility of exploiting the new degrees of freedom afforded by field of multimode nonlinear fiber optics.

Axially-offset differential interference contrast microscopy via polarization wavefront shaping.

Sample-scan phase contrast imaging was demonstrated by producing and coherently recombining light from a pair of axially offset focal planes. Placing a homogeneous medium in one of the two focal planes enables quantitative phase imaging using only common-path optics, recovering absolute phase without halo or oblique-illumination artifacts. Axially offset foci separated by 70 μm with a 10x objective were produced through polarization wavefront shaping using a matched pair of custom-designed microretarder arrays, compatible with retrofitting into conventional commercial microscopes.

Spatially encoded polarization-dependent nonlinear optics.

A single fixed optic is combined with the sample translation capabilities inherent to most microscopes to achieve precise polarization-dependent second harmonic generation microscopy measurements of thin tissue sections. Although polarization measurements have enabled detailed structural analysis of collagen, challenges in integrating rotation stages or fast electro-optic/photoelastic modulation have complicated the retrofitting of existing systems for precise polarization analysis. Placing a static microretarder array in the rear conjugate plane resulted in spatially encoded polarization modulation across the field of view.

Gene Expression Profiling of Lacrimal Glands Identifies the Ectopic Expression of MHC II on Glandular Cells as a Presymptomatic Feature in a Mouse Model of Primary Sjögren's Syndrome.

Ectopic expression of MHC II molecules on glandular cells is a feature of primary Sjögren's syndrome (pSS). However, the cause of this ectopic expression and its potential role in the pathogenesis of the disease remains elusive. Here, we report that ectopic expression of MHC II molecules on glandular cells represents an early presymptomatic event in a mouse model of pSS induced by immunization of Ro60_316-335 peptide emulsified in TiterMax® as an adjuvant.

Differing Outcome of Experimental Autoimmune Encephalitis in Macrophage/Neutrophil- and T Cell-Specific gp130-Deficient Mice.

gp130 cytokines are differentially involved in regulating the T helper (H) 17-driven pathogenesis of experimental autoimmune encephalomyelitis (EAE), the animal model of human multiple sclerosis. Interleukin (IL)-6 directly promotes the development of TH17 cells through the gp130/IL-6R complex. By contrast, IL-27 has been shown to suppress a TH17 immune response by gp130/IL-27R-alpha (α) receptor ligation.

Triboluminescence from Pharmaceutical Formulations.

Triboluminescence (TL) is shown to enable selective detection of trace crystallinity within nominally amorphous solid dispersions (ASDs). ASDs are increasingly used for the preparation of pharmaceutical formulations, the physical stability of which can be negatively impacted by trace crystallinity introduced during manufacturing or storage. In the present study, TL measurements of a model ASD consisting of griseofulvin in polyethylene glycol produced limits of detection of 140 ppm.

Second Harmonic Generation of Unpolarized Light.

A Mueller tensor mathematical framework was applied for predicting and interpreting the second harmonic generation (SHG) produced with an unpolarized fundamental beam. In deep tissue imaging through SHG and multiphoton fluorescence, partial or complete depolarization of the incident light complicates polarization analysis. The proposed framework has the distinct advantage of seamlessly merging the purely polarized theory based on the Jones or Cartesian susceptibility tensors with a more general Mueller tensor framework capable of handling partial depolarized fundamental and/or SHG produced.

B Cells Are Indispensable for a Novel Mouse Model of Primary Sjögren's Syndrome.

Primary Sjögren's syndrome (pSS) is characterized by a panel of autoantibodies, while it is not clear whether B cells and autoantibodies play an essential role in pathogenesis of the disease. Here, we report a novel mouse model for pSS which is induced by immunization with the Ro60_316-335 peptide containing a predominant T cell epitope. After immunization, mice developed several symptoms mimicking pSS, including a decreased secretion of tears, lymphocytic infiltration into the lacrimal glands, autoantibodies, and increased levels of inflammatory cytokines.

CD11b-deficient mice exhibit an increased severity in the late phase of antibody transfer-induced experimental epidermolysis bullosa acquisita.

CD11b, the α-chain of β integrin Mac-1, is involved in many activation processes of phagocytes. Depending on the respective autoimmune disorder, CD11b has been shown to exert pro-inflammatory functions or be dispensable in their pathogenesis. Here, we investigated the role of CD11b in the pathogenesis of experimental epidermolysis bullosa acquisita (EBA), an autoimmune skin blistering disease mediated by autoantibodies to type VII collagen.

Theoretical Foundation for Electric-Dipole-Allowed Chiral-Specific Fluorescence Optical Rotary Dispersion (F-ORD) from Interfacial Assemblies.

Fluorescence optical rotary dispersion (F-ORD) is proposed as a novel chiral-specific and interface-specific spectroscopic method. F-ORD measurements of uniaxial assemblies are predicted to be fully electric-dipole-allowed, with corresponding increases in sensitivity to chirality relative to chiral-specific measurements in isotropic assemblies that are commonly interpreted through coupling between electric and magnetic dynamic dipoles. Observations of strong chiral sensitivity in prior single-molecule fluorescence measurements of chiral interfacial molecules are in excellent qualitative agreement with the predictions of the F-ORD mechanism and challenging to otherwise explain.

Autoantibodies against the Second Extracellular Loop of M3R Do neither Induce nor Indicate Primary Sjögren's Syndrome.

Objectives: Anti-muscarinic acetylcholine type-3 receptor (anti-M3R) autoantibodies have been suggested to be pathogenic for primary Sjögren's syndrome (pSS), and the second extracellular loop of M3R is suspected to carry a disease-promoting epitope. In this study, we aimed to evaluate the pathogenicity of autoantibodies against peptides derived from the second extracellular loop of M3R in mice and to determine whether those autoantibodies could be used as biomarker for pSS.

Methods: BALB/c mice were immunized with modified linear or cyclic peptides of the second extracellular loop of M3R.

Parts per Million Powder X-ray Diffraction.

Here we demonstrate the use of second harmonic generation (SHG) microscopy-guided synchrotron powder X-ray diffraction (PXRD) for the detection of trace crystalline active pharmaceutical ingredients in a common polymer blend. The combined instrument is capable of detecting 100 ppm crystalline ritonavir in an amorphous hydroxypropyl methylcellulose matrix with a high signal-to-noise ratio (>5000). The high spatial resolution afforded by SHG microscopy allows for the use of a minibeam collimator to reduce the total volume of material probed by synchrotron PXRD.

Association of BAFF and IL-17A with subphenotypes of primary Sjögren's syndrome.

Aim: Primary Sjögren's syndrome (pSS) is an autoimmune disease affecting exocrine glands. Both autoreactive T cells and B cells are involved in the development of pSS, but their exact contribution to the pathogenesis is not clear. Here, we aimed to investigate the association of B-cell activating factor (BAFF) and interleukin (IL)-17A with subphenotypes of pSS.

The amino acid variation within the binding pocket 7 and 9 of HLA-DRB1 molecules are associated with primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is associated with HLA-DRB1 loci, but the association of amino acid variations in the hypervariable region of the HLA-DR β1 chain with pSS is largely unknown. In this study, we aimed to identify the amino acid variations within the hypervariable region of HLA-DRB1 molecule which are associated with the susceptibility to pSS. We sequenced the 2nd exon of the HLA-DRB1 locus in 52 pSS patients and 179 controls.

The CH-π interactions of methyl ethers as a model for carbohydrate-N-heteroarene interactions.

CH-π interactions have been cited as an important contributor to carbohydrate recognition. To determine whether N-heterocycles form stronger CH-π interactions, the interactions of methyl ether groups with heterocyclic and nonheterocyclic aromatic surfaces were studied. Both experimental and computational experiments found that N-heterocyclic aromatic surfaces formed stronger interactions.

mtDNA sequence, phylogeny and evolution of laboratory mice.

Laboratory mice are important tools for biomedical research. Aiming to investigate the phylogeny and evolution of laboratory mice, we investigated the mtDNA sequences of classic inbred strains, classic outbred stocks and wild-derived inbred strains. Our results showed that the most classic outbred stocks and classic inbred strains are descended from a single mtDNA ancestor.