A molecular basis for the T cell response in HLA-DQ2.2 mediated celiac disease.

The highly homologous human leukocyte antigen (HLA)-DQ2 molecules, HLA-DQ2.5 and HLA-DQ2.2, are implicated in the pathogenesis of celiac disease (CeD) by presenting gluten peptides to CD4+ T cells. However, while HLA-DQ2.5 is strongly associated with disease, HLA-DQ2.2 is not, and the molecular basis underpinning this differential disease association is unresolved. We here provide structural evidence for how the single polymorphic residue (HLA-DQ2.5-Tyr22α and HLA-DQ2.2-Phe22α) accounts for HLA-DQ2.2 additionally requiring gluten epitopes possessing a serine at the P3 position of the peptide. In marked contrast to the biased T cell receptor (TCR) usage associated with HLA-DQ2.5-mediated CeD, we demonstrate with extensive single-cell sequencing that a diverse TCR repertoire enables recognition of the immunodominant HLA-DQ2.2-glut-L1 epitope. The crystal structure of two CeD patient-derived TCR in complex with HLA-DQ2.2 and DQ2.2-glut-L1 (PFSEQEQPV) revealed a docking strategy, and associated interatomic contacts, which was notably distinct from the structures of the TCR:HLA-DQ2.5:gliadin epitope complexes. Accordingly, while the molecular surfaces of the antigen-binding clefts of HLA-DQ2.5 and HLA-DQ2.2 are very similar, differences in the nature of the peptides presented translates to differences in responding T cell repertoires and the nature of engagement of the respective antigen-presenting molecules, which ultimately is associated with differing disease penetrance.

New 5,5-(1,4-Phenylenebis(methyleneoxy)diisophthalic Acid Appended Zn(II) and Cd(II) MOFs as Potent Photocatalysts for Nitrophenols.

Metal-organic frameworks (MOFs) are peculiar multimodal materials that find photocatalytic applications for the decomposition of lethal molecules present in the wastewater. In this investigation, two new d10-configuration-based MOFs, [Zn2(L)(H2O)(bbi)] (1) and [Cd2(L)(bbi)] (2) (5,5-(1,4-phenylenebis(methyleneoxy)diisophthalic acid (H2L) and 1,1'-(1,4-butanediyl)bis(imidazole) (bbi)), have been synthesized and characterized. The MOF 1 displayed a (4,6)-connected (3.43.52)(32.44.52.66.7) network topology, while 2 had a (3,10)-connected network with a Schläfli symbol of (410.511.622.72)(43)2. These MOFs have been employed as photocatalysts to photodegrade nitrophenolic compounds, especially p-nitrophenol (PNP). The photocatalysis studies reveal that 1 displayed relatively better photocatalytic performance than 2. Further, the photocatalytic efficacy of 1 has been assessed by altering the initial PNP concentration and photocatalyst dosage, which suggest that at 80 ppm PNP concentration and at its 50 mg concentration the MOF 1 can photo-decompose around 90.01% of PNP in 50 min. Further, radical scavenging experiments reveal that holes present over 1 and ·OH radicals collectively catalyze the photodecomposition of PNP. In addition, utilizing density of states (DOS) calculations and Hirshfeld surface analyses, a plausible photocatalysis mechanism for nitrophenol degradation has been postulated.

Determination of oxytetracycline hydrochloride in milk and egg white samples using Ru(bipy)3 2+ -Ce(SO4 )2 chemiluminescence.

A novel, rapid and sensitive chemiluminescence (CL) method for the determination of oxytetracycline hydrochloride (OTCH) is described in this paper. The presented method was based on the fact that OTCH could immensely enhance the CL of the reaction of cerium sulfate and tris(2,2-bipyridyl) ruthenium (II) in acidic medium. Under optimal experimental conditions, CL intensity was favorably linear for OTCH in the range 5.0 × 10-7 to 5.0 × 10-5  g/ml, with a detection limit of 1.5 × 10-7  g/ml (S/N = 3). The relative standard detection was 4.76% for 5.0 × 10-6  g/ml (n = 11). This method was successfully applied to the analysis of OTCH in milk and egg white samples. According to the results of the kinetic curves for OTCH in the Ru(bipy)3 2+ -Ce(SO4 )2 CL system, together with CL and ultraviolet (UV)-visible spectra, the possible mechanism of the CL reaction is discussed briefly.

Correction to: Synergistic effect of a cobalt fluoroporphyrin and graphene oxide on the simultaneous voltammetric determination of catechol and hydroquinone.

The published version of this article, unfortunately, contains error. The author found out that Chart 1 image was wrongly incorporated in the online paper.

Synergistic effect of a cobalt fluoroporphyrin and graphene oxide on the simultaneous voltammetric determination of catechol and hydroquinone.

Graphene oxide (GO) was modified with the cobalt(II) and zinc(II) complexes (CoTFPP and ZnTFPP) of 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin in order to improve the electrocatalytic activity of GO towards catechol (CC) and hydroquinone (HQ). It is found that the CoTFPP-modified GO on a glassy carbon electrode (GCE) displays the highest electrocatalytic activity. The response to CC (at 0.14 V vs. SCE) is linear in the 1-220 µM concentration range. The response to HQ (at 0.04 V vs. SCE) extends from 1 µM to 200 µM. The sensitivity and detection limits are 10.40 µA∙µM-1∙cm-2 and 0.17 µM for CC, and 8.40 µA∙µM-1∙cm-2 and 0.21 µM for HQ. Experimental results indicate that the Co(II) and Zn(II) ions in the porphyrins positively affect the electron transfer rate in the hybrid materials. The GCE modified with CoTFPP/GO was successfully applied to the simultaneous determination of CC and HQ in spiked samples of tap and lake water. Graphical abstract Schematic presentation of a voltammetric method for simultaneous determination of catechol (CC) and hydroquinone (HQ). It is based on the use of a cobalt (II) fluoroporphyrin (CoTFPP) functionalized graphene oxide (GO) hybrid.

A highly Selective Fluorescent Chemosensor for Zn2+ Based on the Rhodamine Derivative Incorporating Coumarin Group.

A coumarin-appended rhodamine derivative was prepared by reacting rhodamine hydrazide and coumarin-3-carboxylic acid, which fluorescence sensing behavior toward Zn2+ against other metal ions was investigated in CH3CN. Significantly, the rodamine-coumarin derivative exhibited highly selective and sensitive recognition toward Zn2+ with a limit of detection (LOD) down to 10-9 M. Upon addition of Zn2+, remarkable fluorescent intensities enhanced and also clear color changed from colorless to pink. The Job's plot indicated the formation of 1:1 complex between the rhodamine-coumarin derivative and Zn2+. The presence of common coexisting alkali, alkaline earth, and transition metal ions showed small or no interference with the detection of Zn2+. The conjugate dye could be used for "naked-eye" detection of Zn2+.

Protective effects of traditional Uighur medicine-seeds of Nigella glandulifera Freyn extracts against ccl4-induced acute hepatic injury in mice.

To explore the protective effects of Traditional Uighur medicine Seeds of Nigella glandulifera Freyn (SNF) extracts against CCl4-induced acute hepatic injury in mice. Hepatic injury mice models induced by intraperitoneal injection of 0.1% CCl4 olive oil were established. Liver and spleen coefficient, Serum ALT and AST activities, SOD, GSH-Px activities and MDA content in hepatic homogenate were measured and the hepatic histological changes were observed by optical microscope. Serum activities of ALT (P<0.01) and AST (P<0.05) in Alcohol extraction group was decreased; Activity of hepatic homogenate SOD increased in Alcohol extraction group and Water extraction group significantly (P<0.05). Content of MDA was decreased in Alcohol extraction group (P<0.01). Water extracts of SNF have obvious protective effects on hepatic injury induced by CCl4 in mice.

[Sexual satisfaction and its associated factors among individuals with hearing disability].

OBJECTIVE: To investigate sexual satisfaction (SS) and the factors associated with decreased SS among individuals with hearing disability. METHODS: We conducted an investigation on SS among 439 individuals (268 males and 171 females, aged ≥18 yr) with hearing disability using a general information questionnaire, Center for Epidemiologic Studies Depression Scale, Social Support Rating Scale, and a self-report on SS. We identified the factors of decreased SS by multivariate ordinal logistic regression analysis. RESULTS: Totally 76 (17.3%) of the hearing-disability individuals investigated were dissatisfied with their sexual life. SS reduction was significantly correlated with the status of being single (OR=1.72), grade-1 or -2 disability (OR=1.78), physical diseases (OR=2.46), depression (OR=6.61), or inadequate subjective social support (OR=3.28). CONCLUSIONS: SS of hearing-disability persons is relatively low, which can be improved by treating physical diseases, promoting mental health, and providing psycho-social support.

Determination of Phenolic Compounds in Environmental Water by HPLC Combination with On-Line Solid-Phase Extraction Using Molecularly Imprinted Polymers.

A novel molecularly imprinted polymer (MIP) was synthesized using halloysite nanotubes (HNT) as matrix, ß-cyclodextrin (ß-CD) and methyl propyl acid (MAA) as functional monomers, and 2,4,6-TCP as template molecule by graft copolymerization. Infrared spectroscopy and transmission electron microscopy (TEM) were used to characterize the as-synthesized imprinted polymer. The selective recognizability of the MIP towards four phenolic analogs were determined and the recognition coefficients for 2,4,6-TCP, 2,6-DCP, 4-CP and phenol were found to be 2.17, 1.85, 2.02 and 1.36, respectively. Using as the packing material of solid-phase extraction, the imprinted polymer has been applied to on-line extraction of the four phenolic compounds in environmental water. The corresponding analytical methods to determine these four phenolic compounds have been developed. Good linear relationships were obtained over the range of 0.05-5.0 mg x L(-1). The average recoveries for spiked samples were in the range of 74.8-97.2%, and the detection limits for 2,4,6-TCP, 2,6-DCP, p-chlorophenol, phenol were 0.19, 0.20, 0.75, 0.73 mg x L(-1), respectively. The method is rapid, accurate and high selectivity. It was feasible for the determination of trace level phenolic compounds in environmental samples.

Quantification of magnetically induced changes in ECM local apparent stiffness.

The stiffness of the extracellular matrix (ECM) is known to influence cell behavior. The ability to manipulate the stiffness of ECM has important implications in understanding how cells interact mechanically with their microenvironment. This article describes an approach to manipulating the stiffness ECM, whereby magnetic beads are embedded in the ECM through bioconjugation between the streptavidin-coated beads and the collagen fibers and then manipulated by an external magnetic field. It also reports both analytical results (obtained by formal modeling and numerical simulation) and statistically meaningful experimental results (obtained by atomic force microscopy) that demonstrate the effectiveness of this approach. These results clearly suggest the possibility of creating desired stiffness gradients in ECM in vitro to influence cell behavior.

Application of a computerised navigation technique to assist arthroscopic anterior cruciate ligament reconstruction.

PURPOSE: Based on biomechanical cadaver studies, anatomical double-bundle reconstruction of the anterior cruciate ligament (ACL) was introduced to achieve better stability in the knee, particularly in respect of rotatory loads. Previously, the success of ACL reconstruction was believed to be mainly dependent on correct positioning of the graft, irrespective of the number of bundles for which computer-assisted surgery was developed to avoid malpositioning of the tunnel. The aim of this study was to compare rotational and translational stability after computer-navigated standard single-bundle and anatomical double-bundle ACL reconstruction. METHODS: The authors investigated 42 consecutive patients who had undergone the single-bundle or double-bundle ACL reconstruction procedure using autogenous hamstring tendon grafts and ENDOBUTTON fixation in patients who had been followed up for a minimum of 24 months. Post-operative anteroposterior and rotational laxity was measured with the KT3000 and compared between groups. RESULTS: Both surgical procedures significantly improve rotational and translational stability compared to the preoperative ACL-deficient knee (P<0.05). No significant differences were registered between groups with regard to anteroposterior displacement of the tibia. The International Knee Documentation Committee (IKDC) and Lysholm scores were significantly higher in the double-bundle group. However, the results were excellent in both groups. CONCLUSIONS: The use of computer-assisted ACL reconstruction, which is a highly accurate method of graft placement, could be useful for inexperienced surgeons to avoid malposition. Long-term results of at least five years are needed to determine whether double-bundle ACL reconstruction, which was associated with improved rotational laxity and significantly better IKDC and Lysholm scores compared to the standard single-bundle ACL reconstruction procedure, exerts an influence in terms of avoiding osteoarthritis or meniscus degeneration.

Ischemic and hemorrhagic strokes in young adults: Comparison of functional outcomes and return to work after stroke.

BACKGROUND: Functional recovery and return to work (RTW) after stroke are important rehabilitation goals that have significant impact on quality of life. Comparisons of functional outcomes and RTW between ischemic stroke (IS) and hemorrhagic stroke (HS), especially among young adults with stroke, have either been limited or yielded inconsistent results. We aimed to assess functional outcomes and ability to RTW in young adults with IS and HS, specifically primary spontaneous intracranial hemorrhage (SICH). METHODS: Young adults with IS or SICH aged 18-50-years-old were included. Outcome measures were modified Rankins score (mRS) on discharge and 3-months and RTW at 3-months after stroke. Good functional outcome was defined as an mRS of 0-2. RESULTS: We included 459 patients (71.5% male) with a mean age of 43.3 ± 5.7 years, comprising 49.2% IS and 50.8% SICH. Patients with SICH were more likely to have unfavourable shifts in ordinal mRS on discharge (OR 7.52, CI 5.18-10.87, p < 0.001) and at 3-months (OR 6.41, CI 4.17-9.80, p < 0.001). Patients with IS more likely achieved good functional outcomes (80.2% vs. 51.8%, p < 0.001) and were able to RTW at 3-months (54.4% vs. 36.3%, p = 0.004). Among all stroke patients with good functional outcomes, one-third did not RTW at 3-months. Patients with longer length of hospitalisation and higher National Institutes of Health Stroke Scale (NIHSS) score on admission, especially in the domain categories of level of consciousness, vision, motor function, language and neglect, were less likely to RTW at 3-months. CONCLUSION: Patients with IS were more likely to RTW when compared to SICH patients. Many young stroke patients did not RTW despite good functional outcomes. Further research should therefore address differences in prognosis and identify predictors that influence ability to RTW after stroke in the young adult population.

Self-assembly of L-cysteine for chiral recognition of mandelic acid in gas phase.

This study demonstrates a new approach for the selective recognition of chiral mandelic acid by quartz crystal microbalance (QCM) using L-cysteine as the selector. The modification of L-cysteine on the QCM sensor was identified using resonant frequency detection, the contact angle, cyclic voltammetry, and X-ray photoelectron spectroscopy measurements. The chiral recognizability of L- and D-MA on the L-cysteine-modified surface was examined using QCM detection integrated with a vapor diffused molecular assembly reaction technique. The present chiral recognition results suggest that the L-cysteine is a good resolving agent for detecting chiral mandelic acid.

Co-disposal and reutilization of municipal solid waste and its hazardous incineration fly ash.

Compared to landfill, MSW incineration (MSWI) not only eliminates its innate secondary pollution and land occupation, but also yields a net emission reduction. Regretfully, MSWI produces hazardous incineration fly ash (IFA) enriched with potentially toxic elements and dioxins. Given these, a harmless integrated scenario of co-disposal and resource reutilization of MSW and its hazardous IFA is proposed and subjected to technical and economic analysis. It introduces an IFA melting furnace, as an onsite modular integration, which serves as a bridge between the MSW incinerator and the commercial rock wool production line. The incinerator burns MSW for heating and electricity supply. The melting furnace further burns out the highly toxic dioxins adsorbed on IFA, as well as solidifying the potentially toxic elements into the molten slag, which substitutes for basalt as raw materials used for high value-added rock wool production. That achieves collaborative reduction, stabilization, harmlessness and resource reutilization of MSW as an energy source, and its IFA as energy-saving materials, as well as a net carbon emission reduction and high economicbenefits. Even more exciting, as opposed to the serious losses of the other existing scenarios, it is profitable even without the feed-in tariff and fiscal subsidy, both that are the dominating income source of other scenarios including conventional MSWI & IFA landfill and demonstration MSWI with IFA melting & landfill. Discounted Cash Flow technique shows that the profit is âˆ¼ 9.2 RMB per ton of MSW, and it increases with insulation price, feed-in tariff, and fiscal subsidy. With the feed-in tariff and fiscal subsidy, the existing two scenarios and the proposed harmless integrated scenario can produce revenue of 103.8, 98.1-110.5, and 145.0 RMB per ton of MSW, respectively. Nonetheless, several challenges are posed for future industrial applications, such as liquid slag discharge, unstable combustion and possible environmental issues.

Total pelvic floor reconstruction surgery for repair of severe pelvic organ prolapse.

OBJECTIVE: To evaluate clinical effectiveness of total pelvic floor reconstruction surgery for repair of severe pelvic organ prolapse. METHODS: We retrospectively analyzed the clinical data of 21 patients with severe pelvic organ prolapse. The anatomical outcomes were evaluated by Pelvic Organ Prolapse Quantitation, functional effectiveness by Prolapse Quality of Life method, and sexual function and operation-related complications were also analyzed. RESULTS: All surgical operations were accomplished successfully by the same surgeon. No impairment of bladder, urethra, rectum, or great vessels was noted, and no patient required blood transfusion. The mean operation duration was (63±19) minutes, and the mean intra-operative blood loss was (143±72) ml. One patients experienced post-operative urinary retention for 7 days, and the remaining 20 patients were able to micturate spontaneously 1-2 day after surgery. The post-operative morbidity rate was 14.3%. Three patients (14.3%) experienced mesh erosion. Of 12 patients who were sexually active, two patients suffered from algopareunia from dyspareunia, one from de novo overactive bladder, and one from stress urinary incontinence Questionnaire scores showed that the overall post operative quality of life was improved significantly (P=0.000), while quality of sexual life significantly degraded (P=0.044) The anatomic cure rate was 95.2% (20/21), and the patient subjective satisfaction rate was 85.7% (18/21) CONCLUSIONS: The total pelvic floor reconstruction is a safe and effective approach for the repair of severe pelvic organ prolapse, although its functional effectiveness is not as notable as anatomical outcomes However, the complications such as mesh erosion, low urinary tract symptoms, algopareunia, and dyspareunia should be carefully managed.

From the Genetics of Ankylosing Spondylitis to New Biology and Drug Target Discovery.

Genome-wide association studies (GWAS) have identified 113 single nucleotide polymorphisms (SNPs) affecting the risk of developing ankylosing spondylitis (AS), and an on-going GWAS study will likely identify 100+ new risk loci. The translation of genetic findings to novel disease biology and treatments has been difficult due to the following challenges: (1) difficulties in determining the causal genes regulated by disease-associated SNPs, (2) difficulties in determining the relevant cell-type(s) that causal genes exhibit their function(s), (3) difficulties in determining appropriate cellular contexts to interrogate the functional role of causal genes in disease biology. This review will discuss recent progress and unanswered questions with a focus on these challenges. Additionally, we will review the investigation of biology and the development of drugs related to the IL-23/IL-17 pathway, which has been partially driven by the AS genetics, and discuss what can be learned from these studies for the future functional and translational study of AS-associated genes.

Phylogenetic analysis of the fecal flora of the wild pygmy loris.

The bacterial diversity in fecal samples from the wild pygmy loris was examined with a 16S rDNA clone library and restriction fragment length polymorphism analysis. The clones were classified as Firmicutes (43.1%), Proteobacteria (34.5%), Actinobacteria (5.2%), and Bacteroidetes (17.2%). The 58 different kinds of 16S rDNA sequences were classified into 16 genera and 20 uncultured bacteria. According to phylogenetic analysis, the major genera within the Proteobacteria was Pseudomonas, comprising 13.79% of the analyzed clone sequences. Many of the isolated rDNA sequences did not correspond to known microorganisms, but had high homology to uncultured clones found in human feces.

Probing effects of pH change on dynamic response of Claudin-2 mediated adhesion using single molecule force spectroscopy.

Claudins belong to a large family of transmembrane proteins that localize at tight junctions (TJs) where they play a central role in regulating paracellular transport of solutes and nutrients across epithelial monolayers. Their ability to regulate the paracellular pathway is highly influenced by changes in extracellular pH. However, the effect of changes in pH on the strength and kinetics of claudin mediated adhesion is poorly understood. Using atomic force microscopy, we characterized the kinetic properties of homophilic trans-interactions between full length recombinant GST tagged Claudin-2 (Cldn2) under different pH conditions. In measurements covering three orders of magnitude change in force loading rate of 10(2)-10(4) pN/s, the Cldn2/Cldn2 force spectrum (i.e., unbinding force versus loading rate) revealed a fast and a slow loading regime that characterized a steep inner activation barrier and a wide outer activation barrier throughout pH range of 4.5-8. Comparing to the neutral condition (pH 6.9), differences in the inner energy barriers for the dissociation of Cldn2/Cldn2 mediated interactions at acidic and alkaline environments were found to be <0.65 k(B)T, which is much lower than the outer dissociation energy barrier (>1.37 k(B)T). The relatively stable interaction of Cldn2/Cldn2 in neutral environment suggests that electrostatic interactions may contribute to the overall adhesion strength of Cldn2 interactions. Our results provide an insight into the changes in the inter-molecular forces and adhesion kinetics of Cldn2 mediated interactions in acidic, neutral and alkaline environments.

Chiral recognition of mandelic acid on quartz crystal microbalance by vapor diffused molecular assembly method.

This study presents a new approach for the highly selective recognition of chiral L/D-mandelic acid (MA) using a quartz crystal microbalance (QCM) with L-phenylalanine (L-Phe) as the selector. The immobilization of L-Phe on the gold surface of the QCM sensor was performed using a four steps layer-by-layer assembling procedure. The modification of the gold surface of the QCM sensor after each modification step was verified by the cyclic voltammetry, contact angle, FTIR, and QCM detection. The chiral recognition ability of L- and D-MA on the chiral surface was checked by sensing using the vapor diffused molecular assembly (VDMA) method with the QCM. The chiral discrimination factor between L- and D-MA, aplha(L-MA/D-MA), was found to be about 9. The L-Phe-modified QCM gold sensor also showed good stability and reusability. The high chiral discrimination ability of the modified surface might be the result of the different hydrogen bonding force between L- or D-MA and L-Phe.