High performance polarizer on thin-film lithium niobate with width-tapered Euler bending.

In this Letter, we propose and demonstrate an integrated polarizer on thin film lithium niobate (TFLN). The polarizer consists of a width-tapered 180° Euler bending waveguide featuring thin thickness and bilevel mode convertors with silica cladding. Notably, the TE0 mode is efficiently confined in the waveguide, while the TM0 mode confronts significant bending losses. The measurements reveal that the excess loss remains below 1.5 dB, and the extinction ratio surpasses 19 dB within a working bandwidth spanning from 1480 to 1578 nm. The proposed polarizer holds considerable promise for enhancing polarization handling within TFLN photonic circuits.

Polarization-insensitive and high-efficiency edge coupler for thin-film lithium niobate.

In this Letter, we propose and demonstrate a fiber-to-chip edge coupler (EC) on an x-cut thin film lithium niobate (TFLN) for polarization-insensitive (PI) coupling. The EC consists of three width-tapered full-etched waveguides with silica cladding and matches well with a single-mode fiber (SMF). The measured results show that the minimum coupling losses for TE0/TM0 modes remain to be 0.9 dB/1.1 dB per facet, and the polarization dependent loss (PDL) is <0.5 dB over the wavelength range from 1260 to 1340 nm. Moreover, the EC features large misalignment tolerance of ±2 µm in the Z direction and ±1.5 µm in the X direction for both polarizations for a 1 dB penalty. To the best of our knowledge, this is the first realized O-band edge coupler on TFLN with SMF. The proposed device shows promising potential for integration into TFLN polarization diversity devices.

Fengshi Liuhe Decoction treatment for rheumatoid arthritis via the Fzd6/NF-κB signaling axis.

To explore whether Fengshi Liuhe Decoction (FLD) alleviates rheumatoid arthritis (RA) via the Fzd6/NF-κB signaling axis. We used real-time quantitative PCR (qPCR) and western blotting (WB) to determine the genes of the frizzled (Fzd) protein 1- Fzd protein 10 that are significantly differentially expressed between normal rat fibroblast-like synoviocyte (FLS) and collagen II-induced arthritis (CIA) rat FLS. Next, we used enzyme-linked immunosorbent assay (ELISA) to evaluate the levels of inflammatory factors in cell culture supernatant to determine the ability of FLD to ameliorate RA. Finally, we employed WB to detect the key gene expression in protein levels of the Fzd6/NF-κB signaling axis among normal rat FLS, CIA rat FLS, and FLD-treated CIA rat FLS. Our results showed that Fzd6 expression was significantly higher in CIA rat FLS at both the mRNA and protein levels than in normal rat FLS. FLD was found to downregulate Fzd6 and inflammatory factors, including COX-2, IL-8, and TNF-α, at both the mRNA and protein levels. FLD was also found to downregulate the total protein levels of Fzd6 and the NF-κB signaling pathway key gene phosphorylation of p-p65/p65 and p-IκBα/IκBα. Moreover, FLD inhibited the nuclear translocation of NF-κB p65 in CIA rat FLS. FLD can alleviate inflammation of CIA rat FLS via the Fzd6/NF-κB signaling axis.

All-organic polymeric materials with high refractive index and excellent transparency.

High refractive index polymers (HRIPs) have drawn attention for their optoelectronic applications and HRIPs with excellent transparency and facile preparation are highly demanded. Herein, sulfur-containing all organic HRIPs with refractive indices up to 1.8433 at 589 nm and excellent optical transparency even in one hundred micrometre scale in the visual and RI region as well as high weight-average molecular weights (up to 44500) are prepared by our developed organobase catalyzed polymerization of bromoalkynes and dithiophenols in yields up to 92%. Notably, the fabricated optical transmission waveguides using the resultant HRIP with the highest refractive index display a reduced propagation loss compared with that generated by the commercial material of SU-8. In addition, the tetraphenylethylene containing polymer not only exhibits a reduced propagation loss, but also is used to examine the uniformity and continuity of optical waveguides with naked eyes because of its aggregation-induced emission feature.

Clinical outcomes of unilateral biportal endoscopic lumbar interbody fusion (ULIF) compared with conventional posterior lumbar interbody fusion (PLIF).

BACKGROUND CONTEXT: In recent years, unilateral biportal endoscopic lumbar interbody fusion (ULIF) has been more and more favored by spinal surgeons because of its advantages of low trauma, rapid recovery, high fusion rate and fewer complications. PURPOSE: To compare the clinical effects of ULIF with those of conventional open posterior lumbar interbody fusion (PLIF). STUDY DESIGN: Prospective case control study. PATIENT SAMPLE: Twenty-seven patients treated by ULIF and thirty-three patients treated by PLIF. OUTCOME MEASURES: The preoperative baseline and surgical technique-related outcomes (mean operation time, blood loss during operation, postoperative drainage, and postoperative hospital stay) were compared between the two groups. The clinical status of the two groups before and after surgery were also compared: visual analogue scale (VAS) score of the legs and back, Japanese Orthopedic Association (JOA) score and Oswestry Disability Index (ODI). The clinical laboratory indexes of the two groups before and after the operation were compared: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), creatine phosphokinase (CPK), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), as well as the incidence of complications, such as dural tear, nerve root injury and infection. METHODS: Adult patients who underwent L3-S1 single level lumbar interbody fusion were included in the study. They were divided into a PLIF group and a ULIF group according to the type of surgery. This study comprised 60 cases: 27 cases in the ULIF group and thirty-three cases in the PLIF group. RESULTS: There was no significant difference in preoperative baseline between the two groups. The ULIF group experienced less blood loss, postoperative drainage and a shorter postoperative hospital stay than the PLIF group; however the ULIF group required a longer operation time than the PLIF group (p<.05). CRP, ESR, CPK, IL-6, and TNF-α levels of the PLIF group were all significantly higher than those of the ULIF group 5 days after surgery (p<.05). The improvements in the VAS scores for back pain, VAS scores for leg pain and JOA score in the ULIF group were all significantly better than those in the PLIF group at 5 days after surgery (p<.05). There was no significant difference in fusion rate at 6 months between the 2 groups (p>.05). CONCLUSIONS: This study showed that ULIF and PLIF were both effective surgical techniques for lumbar interbody fusion. However, ULIF caused less bleeding, reduced inflammatory reaction, less tissue damage and faster postoperative recovery compared with PLIF. Both long-term follow-up and larger clinical studies are needed to validate the clinical and radiological results of this surgery.

Standardized Pomegranate (Pomella®) and Red Maple (Maplifa®) Extracts and Their Phenolics Protect Type I Collagen by the Inhibition of Matrix Metalloproteinases, Collagenase, and Collagen Cross-Linking.

Phenolics enriched pomegranate fruit (Pomella®) and red maple leaf (Maplifa®) extracts and their major phenolic constituents have demonstrated beneficial skin effects through the protection of human skin keratinocytes from oxidative-stress-induced damage. However, their mechanisms of protection of cutaneous collagen are still unclear. Herein, the collagen protective effects of Pomella® and Maplifa®, and their major bioactive phytochemicals, namely, punicalagin (PA) and ginnalin A (GA), respectively, were evaluated using enzymatic assays including collagenase, anti-glycation and cell-based models as well as computational methods. The importance of the modulatory effects was validated at the protein level for type I collagen and matrix metalloproteinases (MMPs) using human-skin-derived keratinocytes. The synergistic collagenase inhibitory effects upon combinations of Pomella® + Maplifa® and PA + GA at a combination ratio of 1:2 and 1:1, respectively, were evaluated using their combination index (CI; a well-established assessment of synergism). Pomella® (50-400 µg/mL), Maplifa® (100-800 µg/mL), PA (50-400 µM), and GA (50-400 µM) dose-dependently inhibited collagenase activity by 26.3-86.3%, 25.7-94.0%, 26.2-94.0%, and 12.0-98.0%, respectively. The CI of the anti-collagenase activity of Pomella® and Maplifa® ranged from 0.53-0.90, while that of PA and GA (12.5/12.5 and 25/25 µM) ranged from 0.66 and 0.69, respectively, suggesting a synergistic inhibitory effect. Interestingly, in the cell-based assays by Western blotting, Pomella® and Maplifa® reduced the protein expression levels of collagen degradation enzymes (MMPs), while simultaneously increasing that of type I collagen in epidermoid carcinoma A431 cells. This is the first report to show that these extracts exert synergistic collagen protective effects. Taken together, these findings provide molecular insights into the usefulness of Pomella® and Maplifa® or their phenolics as bioactive ingredients for skin care products to slow down aging and enhance skin tone.

Ultra-compact electro-optic modulator based on etchless lithium niobate photonic crystal nanobeam cavity.

Photonic crystal (PhC) cavities with high Q factor and low volume have been applied in nonlinear, electro-optic and acoustic-optic devices due to the enhancement of the light-matter interactions. However, there are few devices and research on LiNbO3 (LN) PhC cavities due to the difficulty in making hyperfine structures on LN platform. In this work, we propose a PhC nanobeam cavity on the etchless x-cut LiNbO3-On-Insulator (LNOI). The fabrication-friendly device has been designed based on photonic bound states in the continuum (BICs) exhibiting a high Q factor of over 10,000 with the device length of only about 100 µm. Utilizing the electro-optical effect γ13 of LN, we demonstrate an ultra-compact electro-optic modulator based on the PhC nanobeam cavities, which has the modulation efficiency of 1.5 pm/V and the 3 dB bandwidth of 28 GHz.

Photonic-circuited resonance fluorescence of single molecules with an ultrastable lifetime-limited transition.

Resonance fluorescence as the emission of a resonantly-excited two-level quantum system promises indistinguishable single photons and coherent high-fidelity quantum-state manipulation of the matter qubit, which underpin many quantum information processing protocols. Real applications of the protocols demand high degrees of scalability and stability of the experimental platform, and thus favor quantum systems integrated on one chip. However, the on-chip solution confronts several formidable challenges compromising the scalability prospect, such as the randomness, spectral wandering and scattering background of the integrated quantum systems near heterogeneous and nanofabricated material interfaces. Here we report an organic-inorganic hybrid integrated quantum photonic platform that circuits background-free resonance fluorescence of single molecules with an ultrastable lifetime-limited transition. Our platform allows a collective alignment of the dipole orientations of many isolated molecules with the photonic waveguide. We demonstrate on-chip generation, beam splitting and routing of resonance-fluorescence single photons with a signal-to-background ratio over 3000 in the waveguide at the weak excitation limit. Crucially, we show the photonic-circuited single molecules possess a lifetime-limited-linewidth transition and exhibit inhomogeneous spectral broadenings of only about 5% over hours' measurements. These findings and the versatility of our platform pave the way for scalable quantum photonic networks.

Identification and quantification of the combined phytotoxicity of one element with various valences: Cr(III) and Cr(VI) for barley root elongation as an example.

There is uncertainty in quantifying the toxic effects of total chromium (Cr) in the environment by modeling the toxicity of individual Cr(III) or Cr(VI). In the present study, the effects of Cr(III) and Cr(VI) on barley root elongation were investigated in a hydroponic system where Cr(III) and Cr(VI) combination dose-response experiments under monotoxicity concentration, single-dose addition, and fixed concentration ratios were designed to identify and quantify their combined phytotoxicity of one element with various valences. The results show that the calculated mixed toxicity unit values for 50% inhibition (TUmix50) ranged from 1.06 to 1.45, indicating the weak antagonism effects of Cr(III) and Cr(VI) on barley root toxicity. Also, the single-dose group experiment has proved that the EC50 of Cr(VI) was increased from 71.2 µM to 119.9 µM with Cr(III) addition, which suggested that Cr(III) has antagonism on the toxicity of Cr(VI). While EC50 of Cr(III) was not affected by Cr(VI) addition. After introducing the expansion coefficient of Cr(III) on Cr(VI) toxicity, both the extended concentration addition model (e-CA) based on the log-logistic and Weibull equations and the extended independent action model (e-IA) could more accurately predict the barley root elongation under Cr(III) and Cr(VI) interaction. The e-CA model based on the Weibull equation had almost the best correlation coefficient (R2) and lowest root mean square error (RMSE) between the measured and predicted values. Finally, the combined toxicity and antagonism of the same element with co-existing different valences simultaneously were successfully and firstly identified and quantified in the present study.

Association of Toll-like Receptor 4 Rs7873784 G/C Polymorphism with Rheumatoid Arthritis Risk in a Chinese Population.

BACKGROUND: The purposes of this study were to explore whether the Toll-like receptor 4 (TLR4) gene rs7873784 G/C polymorphism was related to the risk of rheumatoid arthritis (RA) and to the clinical features of the disease in Chinese subjects. MATERIALS AND METHODS: We examined the TLR4 rs7873784 G/C polymorphism in 805 Chinese RA patients and 1095 healthy controls. Genotype was determined with a custom-by-design 48-Plex single nucleotide polymorphism scan™ Kit. Blood plasma levels of TLR4 in 170 RA patients and 170 matched controls were measured by ELISA. RESULTS: The TLR4 gene rs7873784 G/C polymorphism was related to a reduced risk for RA. By stratified analysis, we found a dramatically reduced risk for RA in patients who were female, CRP-positive, RF-positive, DAS28 ≥ 3.20, or ESR ≥ 25. Compared with the controls, the average level of TLR4 protein in plasma of RA patients was increased. In addition, RA patients exhibited higher levels of TLR4 mRNA than controls (P < .05). CONCLUSION: These results demonstrate the TLR4 rs7873784 G/C polymorphism to relate to a decreased risk for RA in a Chinese population.

Has previous loan rejection scarred firms from applying for loans during Covid-19?

Abstract: The concept of the 'discouraged' borrower is well documented. In this paper, we consider whether smaller firms in the UK who have been previously rejected for bank loans have been scarred by the experience so badly that even in the presence of two exceptionally generous Covid-19 loan guarantee schemes, they still refuse to make an application. Furthermore, we also consider what happens when they do. As banks have either zero or minimal loss exposure, do they still maintain their normal strict lending protocols or do they relax their standards to fulfil the governments' objective of supporting struggling businesses through the crisis? Our findings show that 72% of previously rejected borrowers are reluctant to request loans. We find some evidence that previously scarred firms faced such severe liquidity problems that they relaxed their distrust of banks during the Covid-19 crisis. However, their share of the government-guaranteed loan portfolio was slightly lower suggesting that banks were treating each new loan application on its merits. Plain English Summary: The Covid-19 crisis hit smaller businesses so hard that even previously rejected borrowers were forced to apply for loans to keep them afloat. Previous loan rejections have not discouraged small businesses in the UK in applying for Covid-19 government-guaranteed loans. Banks have used the loan guarantee schemes to continue to supply loans to small business during the pandemic. Our paper analyses the important phenomenon of borrower scarring and discouragement, when potential debtors are self-excluded from the lending market because they have previous rejections or expect a negative bank response. We consider around 45,000 UK small businesses from 2018 to 2020. On the demand side, we find that the economic shock for small businesses during the pandemic dissipates the scarring effect. Specifically, we find that micro and small businesses had the highest loan demand in the first two quarters of the pandemic (from March 2020). On the supply side, we show that scarred borrowers were not routed onto Covid-19 government-guaranteed loan schemes. These findings show the importance of government-backed lending schemes for small businesses during crisis period. Supplementary Information: The online version contains supplementary material available at 10.1007/s11187-021-00586-2.

Treatment of lower part of glenoid fractures through a novel axillary approach: A case report.

BACKGROUND: Based on the location and size of the fracture block, open reduction and internal fixation can be employed or assisted for shoulder arthroscopy in the treatment of glenoid fractures. However, the treatment of lower part of glenoid fractures through a novel axillary approach has not been reported so far. CASE SUMMARY: A 22-year-old right-handed man was transferred to our outpatient clinic because of right shoulder injury during a traffic accident. X-ray examination after admission suggested the fracture of the lower part of the right glenoid and an ipiselial proximal humeral fracture. Three-dimensional (3D) computed tomography (CT) further suggested that the size of the fracture block of the lower part of the right glenoid was 3.4 mm × 16.2 mm. The patient was diagnosed as the fracture of the lower part of the glenoid, also known as bony Bankart lesion without shoulder dislocation. After general anesthesia, the patient was surgically treated with the open reduction internal fixation through a novel axillary approach. 3D CT and shoulder joint function were reexamined at 12 mo of follow-up, showing acceptable recovery. CONCLUSION: This case report describes a novel axillary approach adopted in an open reduction with cannulated screw and wire anchor internal fixation. After a follow-up for more than 12 mo, 3D CT and shoulder joint function examinations display a good recovery.

HLA-DPB1 rs9277535 polymorphism is associated with rheumatoid arthritis risk in a Chinese Han population.

We used a custom-by-design 48-Plex single nucleotide polymorphism scan™ kit to investigate the relationship between susceptibility to rheumatoid arthritis (RA) and HLA-DPB1 rs9277535 polymorphism in 805 RA patients and 1095 healthy controls from the Chinese Han population. Blood plasma levels of HLA-DPB1 were also examined using enzyme-linked immunosorbent assays in 170 RA patients and 170 matched control individuals. Quantitative reverse transcription PCR (qRT-PCR) was used to evaluate relative HLA-DPB1 mRNA levels in these blood samples as well. The results indicated that some HLA-DPB1 rs9277535 polymorphisms decreased RA susceptibility. Stratified analysis indicated that risk of RA decreased specifically in women and those who were at least 55 years old. In addition, the AG and GG+AG genotypes were associated with CRP status, ACPA status, and ESR in RA patients when the AA genotype was used as the reference group. Furthermore, average HLA-DPB1 plasma levels were increased in RA patients, and HLA-DPB1 plasma levels and mRNA expression were lower in those with the GG genotype than in those with the AA genotype. These results indicate that HLA-DPB1 rs9277535 polymorphism is associated with a decreased risk of RA in the Chinese population.

High-performance all-silicon polarizer with 415 nm bandwidth.

On-chip silicon polarizers have been widely used in polarization controllers. However, there is limited research on all-silicon polarizer covering the whole optical communication band due to the strong waveguide dispersion for silicon waveguides. In this Letter, we demonstrated an all-silicon TE polarizer with high polarization extinction ratio and low insertion loss, working for the whole optical communication band. The device is based on a shallow-etched waveguide realized on a silicon-on-insulator (SOI) platform. The optical field of TE polarization is designed to be tightly confined in the shallow-etched silicon waveguide, while that of TM polarization is weakly confined. As a result, TE polarization propagates through the waveguide with low loss, while TM polarization leaks into the substrate and decays finally. The measurements show that a maximum insertion loss <0.25dB and polarization extinction ratio (PER)>20dB over an ultrabroad operation band from 1260-1675 nm have been achieved for the proposed polarizer.

The Association Between CTLA-4, CD80/86, and CD28 Gene Polymorphisms and Rheumatoid Arthritis: An Original Study and Meta-Analysis.

Background: Rheumatoid arthritis (RA) is related to several pivotal susceptibility genes, including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and costimulatory molecule (CD80/CD86) genes. Although the connection between polymorphisms of CTLA-4 and CD86 genes in different populations of RA have been studied extensively, the results are controversial. Objective: To clarify the correlation in the Chinese Han population between CTLA-4, CD80/86, and CD28 gene polymorphisms, and RA susceptibility. Methods: A case-control study (574 RA patients and 804 controls) was conducted to determine the correlation between CTLA-4 rs231775 and rs16840252 gene polymorphisms, CD86 rs17281995 gene polymorphisms, and the risk of RA for the Chinese Han population. Furthermore, an additional meta-analysis, including three single nucleotide polymorphisms (SNPs) (CTLA-4 rs231775, CTLA-4 rs3087243, and CTLA-4 rs5742909) from 32 citations, including 43 studies, 24,703 cases and 23,825 controls was performed to elucidate the relationship between known SNPs in the CTLA-4 genes and RA for more robust conclusions. Results: The results showed that CTLA-4 rs231775 gene polymorphism decreased the RA risk (GA vs. AA, OR = 0.77, P = 0.025), whereas CTLA-4 rs16840252 and CD86 rs17281995 gene polymorphisms were not related to RA susceptibility. Stratification analyses by RF, ACPA, CRP, ESR, DAS28, and functional class identified significant associations for CTLA-4 rs231775 and rs16840252 gene polymorphisms in the RF-positive and RF-negative groups. A meta-analysis of the literature on CTLA-4 gene polymorphisms and RA risk revealed that the risk of RA was decreased by CTLA-4 rs231775 gene polymorphisms. Conclusions: The CTLA-4 rs231775 gene polymorphism decreased the risk of RA, whereas CTLA-4 rs16840252 and CD86 rs17281995 gene polymorphisms were not related to RA risk. A meta-analysis indicated that CTLA-4 rs231775 and rs3087243 gene polymorphisms decreased the risk of RA. To support these analytical results, additional clinical cases should be investigated in further studies.

Thymocid®, a Standardized Black Cumin (Nigella sativa) Seed Extract, Modulates Collagen Cross-Linking, Collagenase and Elastase Activities, and Melanogenesis in Murine B16F10 Melanoma Cells.

Black cumin (Nigella sativa) seed extract has been shown to improve dermatological conditions, yet its beneficial effects for skin are not fully elucidated. Herein, Thymocid®, a chemically standardized black cumin seed extract, was investigated for its cosmeceutical potential including anti-aging properties associated with modulation of glycation, collagen cross-linking, and collagenase and elastase activities, as well as antimelanogenic effect in murine melanoma B16F10 cells. Thymocid® (50, 100, and 300 µg/mL) inhibited the formation of advanced glycation end-products (by 16.7-70.7%), collagen cross-linking (by 45.1-93.3%), collagenase activity (by 10.4-92.4%), and elastases activities (type I and III by 25.3-75.4% and 36.0-91.1%, respectively). In addition, Thymocid® (2.5-20 µg/mL) decreased melanin content in B16F10 cells by 42.5-61.6% and reduced cellular tyrosinase activity by 20.9% (at 20 µg/mL). Furthermore, Thymocid® (20 µg/mL for 72 h) markedly suppressed the mRNA expression levels of melanogenesis-related genes including microphthalmia-associated transcription factor (MITF), tyrosinase-related protein 1 (TYRP1), and TYRP2 to 78.9%, 0.3%, and 0.2%, respectively. Thymocid® (10 µg/mL) also suppressed the protein expression levels of MITF (by 15.2%) and TYRP1 (by 97.7%). Findings from this study support the anti-aging and antimelanogenic potential of Thymocid® as a bioactive cosmeceutical ingredient for skin care products.

Reducing relative response factor variation using a multidetector approach for extractables and leachables (E&L) analysis to mitigate the need for uncertainty factors.

Characterization of Extractables and Leachables (E&Ls) is an important aspect of product quality in important fields such as pharmaceuticals, medical devices and food contact materials. The main goal of an E&L study is identification and quantification of those species which may leach from packaging materials used to contain pharmaceuticals or which may leach directly out of a medical device or food contact material and thus may result in patient exposure. It is common practice to perform relative quantitation of extractables and leachables using surrogate standards due to the large diversity of species observed and the lack of available reference standards. A key problem in obtaining accurate E&L results arises due to response factor (RF) variation. Different compounds at the same concentration give different signal intensities and thus have different RF values. Two key aspects of study quality are affected by this problem. First, the evaluation of the number of compounds which are above the toxicologically relevant threshold (analytical evaluation threshold, (AET)) can be affected (RF Problem 1: AET Underreporting). Second, quantitative accuracy is affected which can reduce the reliability of the margin of safety (MOS) calculations which serves as the basis of the toxicological evaluation (RF Problem 2: Quantitative Error). RF databases have been the main solution proposed for solving these problems but do not reduce the underlying RF variation and lack the scope required to address quantitative error for compounds not contained in the database. In the absence of other solutions, large uncertainty factors (UF) have been applied in the AET calculations to account for RF Problem 1: AET Underreporting. These UF factors have been assigned values of 4 for GCMS and up to 10 for LCMS. Large uncertainty factors have a number of unintended negative consequences including the need for large amounts of sample concentration (>10X) prior to analysis resulting in potential compound loss or degradation and increased matrix effects. To overcome these problems, this publication demonstrates a multidetector approach using an HPLC system coupled with a Quadrupole Time of Flight Liquid Chromatography Mass Spectrometer (QTOF-LCMS), Charged Aerosol Detector (CAD) and an Ultraviolet-Visible Detector (UV) and a dual detection Gas Chromatography Mass Spectrometry (GCMS) system using a Polyarc Reactor system with Flame Ionization Detection (FID). Herein, it is demonstrated that this combination of methods (the multidetector approach) allowed detection and accurate surrogate standard quantitation of 217 unique extractables spanning a wide range of chemical properties (Mw, logP, pKa and boiling point). The combination of optimized detector selection with appropriate standard selection was verified to provide positive detection for 94% of the compounds at the AET level and a high level of quantitative accuracy (± 20% for 85% of the compounds and ±40% for 91% of the compounds) while using only a UF of 2. Unlike the RF database approach, the multidetector approach is not limited to only those compounds contained in the database but is applicable to the majority of extractables.

Associations of the IL-1B level, IL-1A and IL-1B gene polymorphisms and ankylosing spondylitis risk in a Chinese Han population.

INTRODUCTION: The aim of this study was to investigate the effect of interleukin (IL)-1A and IL-1B gene polymorphisms on ankylosing spondylitis (AS) susceptibility in a Chinese population. Additionally, we examined the association of IL-1B level with different genotype of rs2853550 polymorphism and clinicopathological features of AS patients. MATERIALS AND METHODS: The IL-1B concentration in plasma was determined by an enzyme-linked immunosorbent assay. The IL-1A rs3783546, IL-1A rs3783550 and IL-1B rs2853550 gene polymorphisms were determined by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. RESULTS: Our data indicated that the average plasma IL-1B concentration in the AS patients was markedly higher than in the control samples. Subgroup analyses suggested that there was no significant association between plasma IL-1B concentration and sex, age, HLA-B27, C-reactive protein (CRP), or grade of the sacroiliac joint in AS patients. We also found that the IL-1B rs2853550 AG genotype showed significantly correlation with an increased risk of AS. In comparing AS patients to control participants, elevated plasma concentrations were observed in AS patients while significant differences were found between the IL-1B rs2853550 AA genotypes. There is a negative correlation between the IL-1A rs3783550 and IL-1A rs3783546 polymorphisms in the AS patients in relation to controls. CONCLUSIONS: The IL-1B concentration in plasma was markedly higher in cases and AA genotype carriers. Furthermore, IL-1B rs2853550 AG was a genetic contributor to AS risk in a Chinese population.

The association between RANK, RANKL and OPG gene polymorphisms and the risk of rheumatoid arthritis: a case-controlled study and meta-analysis.

The receptor activator of nuclear factor-κB (RANK) and the osteoprotegerin (OPG) cascade system have been reported to be essential in osteoclastogenesis. In recent years, several studies have investigated the association between polymorphisms of RANK, its ligand RANKL and OPG genes and the risk of rheumatoid arthritis (RA) in different populations. However, the results arising from these studies were conflicting. To determine the association between RANK, RANKL and OPG gene polymorphisms and the risk of RA. We conducted a hospital-based case-controlled study in Changzhou with 574 RA cases and 804 controls. The genotyping of RANK gene rs1805034 polymorphism was conducted by single base extension combined with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). We also undertook a meta-analysis of the literature referring to polymorphisms of RANK, RANKL and OPG genes and RA risk. This case-controlled study found that the polymorphism in the RANK gene rs1805034 was not related to RA risk. Stratification analyses by sex and age suggested that RANK gene rs1805034 polymorphism was not associated with the risk of RA among groups of male, female, age ≤ 55 and age > 55. Our meta-analysis found that the rs2277438 polymorphism in RANKL gene increased the risk of RA, whereas RANK gene rs1805034, OPG gene rs3102735, OPG gene rs2073618, OPG gene rs3134069 polymorphisms were not related to RA susceptibility. In conclusion, this case-controlled study and meta-analysis indicated that the RANKL gene rs2277438 polymorphism increased the RA risk, and that RANK gene rs1805034, OPG gene rs3102735, OPG gene rs2073618, OPG gene rs3134069 polymorphisms were not related to RA risk.

Pentosidine Is Associated With Cortical Bone Geometry and Insulin Resistance in Otherwise Healthy Children.

Pentosidine is an advanced glycation end product (AGE) associated with fracture in adults with diabetes. AGE accumulation in bone collagen contributes to bone fragility but might also adversely influence bone turnover and, consequently, bone geometry. The relationships between AGEs and bone health have yet to be studied in children. Thus, the objective of this study was to assess relationships between pentosidine and cortical bone volumetric density, geometry, and estimated strength in children. Participants were otherwise healthy black and white boys and girls, ages 9 to 13 years, who were at sexual maturation stage 2 or 3 (N = 160). Tibia and radius cortical bone and muscle area (66% site) were assessed via pQCT. In fasting sera, insulin, glucose, and pentosidine were measured. The Quantitative Insulin Sensitivity Check Index (QUICKI), a measure of insulin sensitivity, was calculated. While controlling for race, sex, maturation, and height, pentosidine negatively correlated with QUICKI (P < 0.05). In unadjusted analyses, pentosidine was associated with lower radius and tibia cortical volumetric bone mineral density, bone mineral content (Ct.BMC), area (Ct.Ar), and thickness (Ct.Th); a larger radius endosteal circumference (Endo.Circ); and lower tibia polar strength strain index (all P < 0.05). While controlling for race, sex, maturation, height, and muscle area, pentosidine was negatively associated with tibia Ct.BMC, Ct.Ar, and Ct.Th but positively associated with Endo.Circ (all P < 0.05). Linear regression revealed a significant interaction between pentosidine and QUICKI in relation to tibia Ct.Th (pinteraction = 0.049), indicating that the negative relationship between pentosidine and Ct.Th was stronger in those with lower QUICKI (ie, greater insulin resistance). This is the first study to report evidence of a potentially adverse influence of AGEs on bone strength in otherwise healthy children. This relationship was strongest in children with the greatest insulin resistance, supporting further work in youth with chronic metabolic health conditions. © 2019 American Society for Bone and Mineral Research.