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BackgroundIn observational studies, the relationship between coffee intake and bone mineral density (BMD) is contradictory. However, residual confounding tends to bias the results of these studies. Therefore, we used a two-sample Mendelian randomization (MR) approach to further investigate the potential causal relationship between the two.MethodsGenetic instrumental variables (IVs) associated with coffee intake were derived from genome-wide association studies (GWAS) of the Food Frequency Questionnaire (FFQ) in 428,860 British individuals and matched using phenotypes in PhenoScanner. Summarized data on BMD were obtained from 537,750 participants, including total body BMD (TB-BMD), TB-BMD in five age brackets ≥60, 45-60, 30-45, 15-30, and 0-15 years, and BMD in four body sites: the lumbar spine, the femoral neck, the heel, and the ultradistal forearm. We used inverse variance weighting (IVW) methods as the primary analytical method for causal inference. In addition, several sensitivity analyses (MR-Egger, Weighted median, MR-PRESSO, Cochran’s Q test, and Leave-one-out test) were used to test the robustness of the results.ResultsAfter Bonferroni correction, Coffee intake has a potential positive correlation with total body BMD (effect estimate [Beta]: 0.198, 95% confidence interval [Cl]: 0.05-0.35, P=0.008). In subgroup analyses, coffee intake was potentially positively associated with TB-BMD (45-60, 30-45 years) (Beta: 0.408, 95% Cl: 0.12-0.69, P=0.005; Beta: 0.486, 95% Cl: 0.12-0.85, P=0.010). In addition, a significant positive correlation with heel BMD was also observed (Beta: 0.173, 95% Cl: 0.08-0.27, P=0.002). The results of the sensitivity analysis were generally consistent.ConclusionThe results of the present study provide genetic evidence for the idea that coffee intake is beneficial for bone density. Further studies are needed to reveal the biological mechanisms and offer solid support for clinical guidelines on osteoporosis prevention.

BackgroundObservational studies have shown that changes in circulating cytokine/growth factor levels occur throughout the initiation and progression of ankylosing spondylitis (AS), yet whether they are etiologic or downstream effects remains unclear. In this study, we performed a summarized-level bidirectional Mendelian randomization (MR) analysis to shed light on the causal relationship between the two.MethodsGenetic instrumental-variables (IVs) associated with circulating cytokine/growth factor levels were derived from a genome-wide association study (GWAS) of 8,293 European individuals, whereas summary data for the AS were obtained from a FinnGen GWAS of 166,144 participants. We used the inverse-variance-weighted (IVW) method as the main analysis for causal inference. Furthermore, several sensitivity analyses (MR-Egger, weighted median, MR-PRESSO and Cochran’s Q test) were utilized to examine the robustness of the results. Finally, reverse MR analysis was performed to assess reverse causality between AS and circulating cytokine/growth factor levels.ResultsAfter Bonferroni correction, circulating levels of Cutaneous T-cell attracting (CTACK) and Monocyte specific chemokine 3 (MCP-3) were positively associated with a higher risk of AS (odds ratio [OR]: 1.224, 95% confidence interval [95% Cl]: 1.022 ~ 1.468, P = 0.028; OR: 1.250, 95% Cl: 1.016 ~ 1.539, P = 0.035). In addition, elevated circulating levels of Basic fibroblast growth factor (FGF-basic), Granulocyte colony-stimulating factor (G-CSF) and MCP-3 was considered a consequence of AS disease (β = 0.023, P = 0.017; β = 0.017, P = 0.025; β = 0.053, P = 0.025). The results of the sensitivity analysis were generally consistent.ConclusionThe present study supplies genetic evidence for the relationship between circulating cytokine levels and AS. Targeted interventions of specific cytokines may help to reduce the risk of AS initiation and progression.

Abstract Tumor‐associated macrophages (TAMs) play critical roles in reprogramming other immune cells and orchestrating antitumor immunity. However, the interplay between TAMs and tumor cells responsible for enhancing immune evasion remains insufficiently understood. Here, we revealed that interleukin (IL)‐1β was among the most abundant cytokines within the in vitro tumor‐macrophage coculture system, and enhanced IL‐1β expression was associated with impaired cytotoxicity of CD8+ T cells in human ovarian cancer, indicating the possibility that IL‐1β mediated immunosuppression during tumor‐TAMs crosstalk. Mechanistically, we demonstrated that IL‐1β significantly boosted programmed death‐ligand 1 (PD‐L1) expression in tumor cells via the activation of the nuclear factor‐κb signaling cascade. Specifically, IL‐1β released from TAMs was triggered by lactate, the anaerobic metabolite of tumor cells, in an inflammasome activation‐dependent manner. IL‐1β sustained and intensified immunosuppression by promoting C‐C motif chemokine ligand 2 secretion in tumor cells to fuel TAMs recruitment. Importantly, IL‐1β neutralizing antibody significantly curbed tumor growth and displayed synergistic antitumor efficacies with anti‐PD‐L1 antibody in tumor‐bearing mouse models. Together, this study presents an IL‐1β‐centered immunosuppressive loop between TAMs and tumor cells, highlighting IL‐1β as a candidate therapeutic target to reverse immunosuppression and potentiate immune checkpoint blockade.

The long-term reliability of InZnO (IZO) thin film transistors (TFTs) under a hydrogen-containing environment is researched. Hydrogen incorporation induces hydroxyl groups and oxygen vacancies, leading to the generation of electrons and extra random trap/emission processes in the IZO films. Consequently, the electrical properties and low frequency noise characteristics of IZO TFTs are deteriorated under the long-term hydrogen treatment. Additionally, the recovery characteristics of IZO TFTs after the hydrogen treatment demonstrate that the hydrogen induced hydroxyl groups and oxygen vacancies remain stable at room temperature. The oxygen vacancies can be eliminated, while the hydroxyl groups may still exist at a high temperature. These results may provide useful guidelines in the design and application of IZO TFTs.

Abstract Background Osteoporotic thoracolumbar burst fracture (OTLBF) is common in seniors. Due to the fracture of the posterior vertebra and spinal canal occupancy, the risk of cement leakage and spine injury is high in OTLBF patients, thus the application of vertebroplasty and kyphoplasty is limited in these patients. This study aims to investigate the efficacy and safety of the modified percutaneous kyphoplasty (MPKP) in the treatment of OTLBF. Methods Clinical data of the OTLBF patients treated with MPKP and the osteoporotic thoracolumbar compression fracture (OTLCF) patients undergone PKP from January 2014 to June 2016 were collected. The key procedure of the MPKP was to fill the bone cavity with gel-foam by the first balloon inflation and to press the gel-foam by a second balloon inflation. Pain intensity, Oswestry disability index (ODI), and bone cement leakage of the patients in the two groups were analyzed. Results In the burst fracture group, the overall spinal canal occupancy was relatively low, and the maximum occupancy was 1/3 of the sagittal diameter of the spinal canal. The surgical duration was longer in the burst fracture group (39.0 ± 5.0 min with 95% CI: 37.7, 40.3) than in the compression fracture group (31.7 ± 4.3 min with 95% CI: 31.1, 32.3), and the difference between the two groups was statistically significant (Z = -8.668 and P = 0.000). Both the Oswestry disability index (ODI) and the visual analog scales (VAS) were apparently improved, but there was no significant difference between the two groups. Cement leakage occurred in 13 out of the 53 cases (24.5%) in the burst fracture group and 35 out of the 193 cases (18.1%) in the compression fracture group, and there was no significant difference between the two groups (Z = − 1.038 and P = 0.299). Neither group had consequential symptoms, such as spinal cord lesion, pain, and numbness of the peripheral nerve. Conclusion Similar to the efficacy of PKP in the treatment of OTLCF, MPKP efficiently reduced the cement leakage rate and improved the safety of the surgery, although it prolonged the surgical duration and introduced more surgical steps.

Scaling down effects on conduction and low frequency noise characteristics are investigated in a set of p-type polycrystalline silicon thin-film transistors (poly-Si TFTs) with fixed channel width ( $W=8 \mu$ m) and different channel lengths ( $L=2, 4, 8, 12, ~\text{and}~ 20 \mu$ m). First, short channel effects on threshold voltage, field effect mobility, and sub-threshold swing are examined, while the presence of contact may induce to the degradation of field effect mobility in the short channel devices. Subsequently, the drain current noise power spectral densities are measured at varied effective gate voltages and drain currents. The slopes of normalized noise against effective gate voltage are varied from −1.1 to −2 with decreasing channel length, which indicates that poly-Si TFTs varied from bulk dominated devices to interface dominated devices. Based on $\Delta N-\Delta \mu$ model, the flat-band voltage noise spectral density and coulomb scattering coefficient are extracted. Therefore, measured normalized noises are simulated by considering of contact resistance. Finally, short channel effects on some noise parameters (such as Hooge’s parameter, etc.) are studied and discussed.

Combined spinal-epidural analgesia (CSEA) is sometimes used for difficult births, but whether it contributes to postpartum pelvic muscle disorder is unclear. This randomized controlled trial examined whether CSEA given during labor affects the electrophysiological index of postpartum pelvic floor muscle function.A consecutive sample of primiparous women who delivered vaginally at term were randomly assigned to a CSEA group (n = 143) and control group (n = 142) between June 2013 and June 2014. All were assessed 6-8 weeks later for electrophysiological function of pelvic floor muscle.The two groups were similar in the degree of muscle strength, muscle fatigue, and pelvic dynamic pressure of pelvic floor muscle. The CSEA and control groups showed similar proportions of women with normal muscle strength (score ≥4) in type I pelvic fibers (23.1% vs. 14.1%, P = 0.051) and type II pelvic fibers (28.0% vs. 24.6%, P = 0.524). The groups also contained similar proportions of women who showed no fatigue in type I fibers (54.5% vs. 48.6%, P = 0.315) or type II fibers (88.8% vs. 87.3%, P = 0.699). Similarly low proportions of women in the CSEA group and control group showed normal pelvic dynamic pressure (11.2% vs. 7.7%, P = 0.321). However, women in the CSEA group spent significantly less time in labor than those in the control group (7.25 vs. 9.52 h, P

Background: Observational studies have shown that changes in circulating cytokine/growth factor levels occur throughout the initiation and progression of ankylosing spondylitis (AS), yet whether they are etiologic or downstream effects remains unclear. In this study, we performed a summarized-level bidirectional Mendelian randomization (MR) analysis to shed light on the causal relationship between the two. Methods: Genetic instrumental-variables (IVs) associated with circulating cytokine/growth factor levels were derived from a genome-wide association study (GWAS) of 8,293 European individuals, whereas summary data for the AS were obtained from a FinnGen GWAS of 166,144 participants. We used the inverse-variance-weighted (IVW) method as the main analysis for causal inference. Furthermore, several sensitivity analyses (MR-Egger, weighted median, MR-PRESSO and Cochran's Q test) were utilized to examine the robustness of the results. Finally, reverse MR analysis was performed to assess reverse causality between AS and circulating cytokine/growth factor levels. Results: After Bonferroni correction, circulating levels of Cutaneous T-cell attracting (CTACK) and Monocyte specific chemokine 3 (MCP-3) were positively associated with a higher risk of AS (odds ratio [OR]: 1.224, 95% confidence interval [95% Cl]: 1.022 ~ 1.468, P = 0.028; OR: 1.250, 95% Cl: 1.016 ~ 1.539, P = 0.035). In addition, elevated circulating levels of Basic fibroblast growth factor (FGF-basic), Granulocyte colony-stimulating factor (G-CSF) and MCP-3 was considered a consequence of AS disease (β = 0.023, P = 0.017; β = 0.017, P = 0.025; β = 0.053, P = 0.025). The results of the sensitivity analysis were generally consistent. Conclusion: The present study supplies genetic evidence for the relationship between circulating cytokine levels and AS. Targeted interventions of specific cytokines may help to reduce the risk of AS initiation and progression. [ABSTRACT FROM AUTHOR]

In this article, a new compact metasurface circularly polarized (CP) antenna is presented, where the rotating 45° periodic ellipse patch is used to achieve polarization conversion from linearly polarized to CP. The meta‐surface is composed of 4 × 4 ellipse patches with 45° rotation, which are etched on the top layer of upper substrate. A slot ground plane and a coplanar waveguide structure are printed on both sides of bottom substrate, and the bottom substrate is directly connected to the upper substrate, which can make the antenna profile lower. As demonstrated in this article, the presented antennas have good characteristics of excellent 3‐dB axial ratio bandwidth of 17.4% (5.25‐6.25 GHz), and wide 10‐dB impedance bandwidth of 20.6% (5.0‐6.15 GHz). [ABSTRACT FROM AUTHOR]

BackgroundIt has been reported that microRNA-130a (miR-130a) targets GAX, the growth arrest-specific homeobox, which inhibits proliferation, differentiation, and migration of vascular smooth muscle cells (VSMCs). In the present study, we therefore investigated the effect of miR-130a on proliferation of cultured VSMCs and the potential role of miR-130a in vascular remodeling during hypertension.MethodsProliferation of VSMCs was determined by 5-bromo-2′-deoxyuridine (BrdU) incorporation method. The expression of miR-130a and GAX was analyzed by quantitative reverse transcription-PCR. The protein expression of GAX was analyzed by western blot. The mimic and inhibitor of miR-130a were used in gain-of-function and loss-of-function in vitro studies, respectively. The correlation of miR-130a with vascular remodeling was observed in spontaneously hypertensive rats (SHRs).ResultsMiR-130a mimic at the concentration of 25 or 50 nmol/l significantly promoted proliferation of VSMCs. The expression of miR-130a was upregulated in the remodeled aorta and superior mesenteric artery of SHRs. The expression of GAX was downregulated in VSMCs transfected with miR-130a mimic and in thoracic aorta and superior mesenteric artery of SHRs. Angiotensin II (Ang II) promoted proliferation of VSMCs and upregulated miR-130a expression concomitantly with a decreased GAX expression in a concentration- and time-dependent manner. The proliferative effects of Ang II on VSMCs were suppressed partly by the miR-130a inhibitor.ConclusionsThese results suggest that miR-130a is a novel regulator of proliferation of VSMCs via inhibiting the expression of GAX, which may contribute to vascular remodeling in hypertension.American Journal of Hypertension (2011). doi:10.1038/ajh.2011.116 [ABSTRACT FROM AUTHOR]

To explore the effects of cariporide, a selective sodium-hydrogen antiporter inhibitor, on endothelial dysfunction induced by high glucose.Acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR), sodium nitroprusside (SNP)-induced endothelium-independent relaxation and biochemical parameters including malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) were measured in rat isolated aorta.A 6-h incubation of aortic rings with high glucose (44 mmol/L) resulted in a significant inhibition of EDR, but had no effects on endothelium-independent relaxation. After the 6-h incubation of aortic rings in the co-presence of cariporide (0.01, 0.1, and 1μmol/L) with high glucose, cariporide prevented the inhibition of EDR caused by high glucose in concentration-dependent manners. Similarly, high glucose decreased SOD activity and contents of NO, and increased MDA concentration in aortic tissue. Cariporide (1μmol/L) significantly resisted the decrease of NO content and SOD activity, and elevation of MDA concentration caused by high glucose in aortic tissues. Mannitol (44 mmol/L) or cariporide (1μmol/L) alone had no effect on EDR, endothelium-independent relaxation and biochemical parameters.Cariporide significantly prevented endothelial dysfunction induced by high glucose. The mechanisms of endothelial dysfunction induced by high glucose may involve the activation of sodium-hydrogen antiporter and the generation of oxygen-free radicals, but it is not related to the change of osmolarity. [ABSTRACT FROM AUTHOR]

The transfer characteristics of amorphous indium-zinc-oxide thin film transistors are measured in the temperature range of 10–400 K. The variation of electrical parameters (threshold voltage, field effect mobility, sub-threshold swing, and leakage current) with decreasing temperature are then extracted and analyzed. Moreover, the dominated carrier transport mechanisms at different temperature regions are investigated. The experimental data show that the carrier transport mechanism may change from trap-limited conduction to variable range hopping conduction at lower temperature. Moreover, the field effect mobilities are also extracted and simulated at various temperatures. [ABSTRACT FROM AUTHOR]