Neutrophil extracellular trap production and CCL4L2 expression influence corticosteroid response in asthma.

The association between neutrophil extracellular traps (NETs) and response to inhaled corticosteroids (ICS) in asthma is unclear. To better understand this relationship, we analyzed the blood transcriptomes from children with controlled and uncontrolled asthma in the Taiwanese Consortium of Childhood Asthma Study using weighted gene coexpression network analysis and pathway enrichment methods. We identified 298 uncontrolled asthma-specific differentially expressed genes and one gene module associated with neutrophil-mediated immunity, highlighting a potential role for neutrophils in uncontrolled asthma. We also found that NET abundance was associated with nonresponse to ICS in patients. In a neutrophilic airway inflammation murine model, steroid treatment could not suppress neutrophilic inflammation and airway hyperreactivity. However, NET disruption with deoxyribonuclease I (DNase I) efficiently inhibited airway hyperreactivity and inflammation. Using neutrophil-specific transcriptomic profiles, we found that CCL4L2 was associated with ICS nonresponse in asthma, which was validated in human and murine lung tissue. CCL4L2 expression was also negatively correlated with pulmonary function change after ICS treatment. In summary, steroids fail to suppress neutrophilic airway inflammation, highlighting the potential need to use alternative therapies such as leukotriene receptor antagonists or DNase I that target the neutrophil-associated phenotype. Furthermore, these results highlight CCL4L2 as a potential therapeutic target for individuals with asthma refractory to ICS.

Enhancing optical characteristics of mediator-assisted wafer-scale MoS2and WS2on h-BN.

Two-dimensional (2D) materials and their heterostructures exhibit intriguing optoelectronic properties; thus, they are good platforms for exploring fundamental research and further facilitating real device applications. The key is to preserve the high quality and intrinsic properties of 2D materials and their heterojunction interface even in production scale during the transfer and assembly process so as to apply in semiconductor manufacturing field. In this study, we successfully adopted a wet transfer existing method to separate mediator-assisted wafer-scale from SiO2/Si growing wafer for the first time with intermediate annealing to fabricate wafer-scale MoS2/h-BN and WS2/h-BN heterostructures on a SiO2/Si wafer. Interestingly, the high-quality wafer-scale 2D material heterostructure optical properties were enhanced and confirmed by Raman and photoluminescence spectroscopy. Our approach can be applied to other 2D materials and expedite mass production for industrial applications.

Circuit quantum electrodynamics with dressed states of a superconducting artificial atom.

A dynamical control of the coupling strengths between dressed states and probe photon states is demonstrated with a transmon-like artificial atom coupled to two closely spaced resonant modes. When the atom is driven with one mode, the atom state and driving photon states form the so-called dressed states. Dressed states with sideband index up to 3 were prepared and probed via the strong coupling to the other resonant mode. Spectroscopy reveals that the coupling strengths are "dressed" and can be modulated by the power and sideband index of the driving. The transmission of the probe tone is modulated by the driving microwave amplitude with a Bessel behavior, displaying multi-photon process associated with the inter-atomic level transitions.

Taiwan axion search experiment with haloscope: Designs and operations.

We report on a holoscope axion search experiment near 19.6 µeV from the Taiwan Axion Search Experiment with Haloscope collaboration. This experiment is carried out via a frequency-tunable cavity detector with a volume V = 0.234 liter in a magnetic field B0 = 8 T. With a signal receiver that has a system noise temperature Tsys ≅ 2.2 K and an experiment time of about one month, the search excludes values of the axion-photon coupling constant gaγγ ≳ 8.1 × 10-14 GeV-1, a factor of 11 above the Kim-Shifman-Vainshtein-Zakharov benchmark model, at the 95% confidence level in the mass range of 19.4687-19.8436 µeV. We present the experimental setup and procedures to accomplish this search.

First Results from the Taiwan Axion Search Experiment with a Haloscope at 19.6 µeV.

This Letter reports on the first results from the Taiwan Axion Search Experiment with a Haloscope, a search for axions using a microwave cavity at frequencies between 4.707 50 and 4.798 15 GHz. Apart from the nonaxion signals, no candidates with a significance of more than 3.355 were found. The experiment excludes models with the axion-two-photon coupling |g_{aγγ}|≳8.1×10^{-14} GeV^{-1}, a factor of eleven above the benchmark Kim-Shifman-Vainshtein-Zakharov model, in the mass range 19.4687

Subcutaneous anterior pelvic bridge - an innovative technique for fixation of selective acetabular fracture: a case series and literature review.

INTRODUCTION: The aim of the study was to introduce an innovative technique involving the use of a subcutaneous anterior pelvic bridge (SAPB) in the treatment of selective acetabular fractures. METHODS: We performed a retrospective study of 21 patients with acetabular fracture who were treated with SAPB between January 2016 and March 2021. The patients' data were retrieved from electronic charts. Radiological results were evaluated according to the Matta system to assess the quality of the reduction and time of union. Functional outcomes were assessed in line with the d'Aubigné and Postel scoring system. Post-operative complications were also recorded. RESULTS: SAPB required around 60 minutes, with minimal blood loss and short learning curve. Matta score revealed excellent radiological outcomes in seventeen displaced fractures with seven excellent outcomes and nine good outcomes. Functional outcomes were excellent in twelve hips, good in seven hips, and fair in two hips. Six patients had transient lateral femoral cutaneous nerve palsy. DISCUSSION: The innovative SAPB method for the treatment of selective acetabular fracture is proven to be a feasible method with promising outcomes. SAPB is a minimally invasive technique and strengthens the stability of fixation, with less blood loss and fewer intra-operative/post-operative complications.

Risk of Spine Surgery in Patients with Rheumatoid Arthritis: A Secondary Cohort Analysis of a Nationwide, Population-Based Health Claim Database.

Background and Objectives: To study the risk of spine surgery, including cervical and lumbar spine surgeries in patients with rheumatoid arthritis (RA) compared with those without a diagnosis of RA. Materials and Methods: This is a secondary data analysis using population-based health claim data. We identified newly diagnosed adult patients with RA between January 2000 and December 2012, according to the International Classification of Diseases, Ninth revision, clinical modification code 714.0 from Taiwan's National Health Insurance Research Database. Using data frequency-matched by 10-year age intervals, sex and index year with the RA cohort at a ratio of 5:1, we assembled a comparison cohort. All patients were followed until the study outcomes occurred (overall spine surgery, cervical spine surgery, or lumbar spine surgery) or the end of follow-up. Adjusted incidence rate ratios (aIRR) were calculated using Poisson regression analysis with age group, socioeconomic status, geographical region, and osteoporosis included as potential confounders. Results: We identified 1287 patients with RA and 6435 patients without RA. The incidence of overall spine surgery (aIRR = 2.13, 95% confidence interval (CI) = 1.49-3.04) and lumbar spine surgery (aIRR = 2.14, 95% CI = 1.46-3.15) were all significantly higher in the RA cohort. Moreover, females over 45 years of age were particularly at risk for lumbar spine surgery. In RA patients, older age and the combination with the diagnosis of osteoporosis had an elevated risk for overall and lumbar spine surgery. Conclusion: Patients with RA had an increased risk of receiving spine surgery. Physicians should be vigilant for possible spinal problems in women and older patients with RA.

Prenatal antioxidant-enriched and pro-oxidant-contained food, IL4 and IL13 pathway genes, and cord blood IgE.

Prenatal oxidative balance might influence cord blood IgE (cIgE) levels. We aimed to explore if certain prenatal dietary sources of antioxidants and pro-oxidants are associated with cIgE elevation and if they interact with IL4 and IL13 pathway genes. A structured questionnaire was completed during the third trimester of pregnancy for 1107 full-term newborns. Surveyed antioxidant-enriched food included fish, shellfish, and fruit, whereas surveyed pro-oxidant-contained food included fried fish sticks and canned fish. Cord blood was collected for measuring cIgE levels and genotyping IL13 rs1800925, rs20541, rs848, IL4 rs2243250, and STAT6 rs324011. Fairly lean fish consumption showed protection against cIgE elevation (odds ratio [OR] 0.66; 95% CI 0.49-0.90) in the whole sample, while daily fruit (OR 0.46; 95% CI 0.27-0.79) and ≥ monthly canned fish (OR 2.81; 95% CI 1.24-6.36) exhibited associations only in genetically susceptible babies. A prenatal food protective index, comprising any fairly lean fish, daily fruit, and the absence of any canned fish, exerted dose-response protection against cIgE elevation in babies carrying the IL13 rs20541 GA or AA genotype (P for trend < 0.0001; P for interaction = 0.004). We concluded that prenatal antioxidant-enriched and pro-oxidant-contained food consumption may influence cIgE, especially in genetically susceptible babies.

Therapeutic Potential of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Recovering From Murine Pulmonary Emphysema Under Cigarette Smoke Exposure.

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were shown to have potential for immunoregulation and tissue repair. The objective of this study was to investigate the effects of hUC-MSCs on emphysema in chronic obstructive pulmonary disease (COPD). The C57BL/6JNarl mice were exposed to cigarette smoke (CS) for 4 months followed by administration of hUC-MSCs at 3 × 106 (low dose), 1 × 107 (medium dose), and 3 × 107 cells/kg body weight (high dose). The hUC-MSCs caused significant decreases in emphysema severity by measuring the mean linear intercept (MLI) and destructive index (DI). A decrease in neutrophils (%) and an increase in lymphocytes (%) in bronchoalveolar lavage fluid (BALF) were observed in emphysematous mice after hUC-MSC treatment. Lung levels of interleukin (IL)-1ß, C-X-C motif chemokine ligand 1 (CXCL1)/keratinocyte chemoattractant (KC), and matrix metalloproteinase (MMP)-12 significantly decreased after hUC-MSC administration. Significant reductions in tumor necrosis factor (TNF)-α, IL-1ß, and IL-17A in serum occurred after hUC-MSC administration. Notably, the cell viability of lung fibroblasts improved with hUC-MSCs after being treated with CS extract (CSE). Furthermore, the hUC-MSCs-conditioned medium (hUC-MSCs-CM) restored the contractile force, and increased messenger RNA expressions of elastin and fibronectin by lung fibroblasts. In conclusion, hUC-MSCs reduced inflammatory responses and emphysema severity in CS-induced emphysematous mice.

Consecutive daily administration of intratracheal surfactant and human umbilical cord-derived mesenchymal stem cells attenuates hyperoxia-induced lung injury in neonatal rats.

BACKGROUND: Surfactant therapy is a standard of care for preterm infants with respiratory distress and reduces the incidence of death and bronchopulmonary dysplasia in these patients. Our previous study found that mesenchymal stem cells (MSCs) attenuated hyperoxia-induced lung injury and the combination therapy of surfactant and human umbilical cord-derived MSCs (hUC-MSCs) did not have additive effects on hyperoxia-induced lung injury in neonatal rats. The aim is to evaluate the effects of 2 consecutive days of intratracheal administration of surfactant and hUC-MSCs on hyperoxia-induced lung injury. METHODS: Neonatal Sprague Dawley rats were reared in either room air (RA) or hyperoxia (85% O2) from postnatal days 1 to 14. On postnatal day 4, the rats received intratracheal injections of either 20 µL of normal saline (NS) or 20 µL of surfactant. On postnatal day 5, the rats reared in RA received intratracheal NS, and the rats reared in O2 received intratracheal NS or hUC-MSCs (3 × 104 or 3 × 105 cells). Six study groups were examined: RA + NS + NS, RA + surfactant + NS, O2 + NS + NS, O2 + surfactant + NS, O2 + surfactant + hUC-MSCs (3 × 104 cells), and O2 + surfactant + hUC-MSCs (3 × 105 cells). The lungs were excised for histological, western blot, and cytokine analyses. RESULTS: The rats reared in hyperoxia and treated with NS yielded significantly higher mean linear intercepts (MLIs) and interleukin (IL)-1ß and IL-6 levels and significantly lower vascular endothelial growth factors (VEGFs), platelet-derived growth factor protein expression, and vascular density than did those reared in RA and treated with NS or surfactant. The lowered MLIs and cytokines and the increased VEGF expression and vascular density indicated that the surfactant and surfactant + hUC-MSCs (3 × 104 cells) treatment attenuated hyperoxia-induced lung injury. The surfactant + hUC-MSCs (3 × 105 cells) group exhibited a significantly lower MLI and significantly higher VEGF expression and vascular density than the surfactant + hUC-MSCs (3 × 104 cells) group did. CONCLUSIONS: Consecutive daily administration of intratracheal surfactant and hUC-MSCs can be an effective regimen for treating hyperoxia-induced lung injury in neonates.

Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells on the Acute Cigarette Smoke-Induced Pulmonary Inflammation Model.

Cigarette smoke (CS) has been reported to induce oxidative stress and inflammatory process in the lungs. However, the role of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in the regulation of pulmonary inflammation remains unclear. The objective of this study is to investigate the effects of hUC-MSCs on lung inflammation in the acute CS-induced pulmonary inflammation animal model. Eight-week-old male C57BL/6 mice were intravenously administered 3 × 106, 1 × 107, and 3 × 107 cells/kg of hUC-MSCs as well as normal saline alone (control) after 3 days of CS exposure. Mice exposed to high-efficiency particulate air (HEPA)-filtered room air served as the CS control group. High-dose (3 × 107 cells/kg) hUC-MSC administration significantly decreased tumor necrosis factor (TNF)-α in the bronchoalveolar lavage fluid (BALF) of CS-exposed mice (p < 0.05). The chemokine (CXC motif) ligand 1/keratinocyte chemoattractant (CXCL1/KC) in BALF were significantly reduced by low-dose (3 × 106 cells/kg) and high-dose (3 × 107 cells/kg) hUC-MSC (p < 0.05). Medium-dose hUC-MSC administration decreased interleukin (IL)-1ß in lung of mice, and TNF-α and caspase-3 were decreased in the lung of CS-exposed mice by medium- and high-dose MSC (p < 0.05). Low-dose hUC-MSCs significantly elevated serum CXCL1/KC and IL-1ß in CS-exposed mice (p < 0.05). Our results suggest that high-dose hUC-MSCs reduced pulmonary inflammation and had antiapoptotic effects in acute pulmonary inflammation.

Optical amplification assisted by two-photon processes in a 3-level transmon artificial atom.

We experimentally study interactions between two microwave fields mediated by 3-level transmon artificial atom with two-photon processes. The transmon has good selection rule, preventing one-photon transition, but allowing two-photon transition from ground state(0) to 2nd excited state(2). By pumping a control tone in resonance to the transition between 1st(1) and 2nd excited state(2), we control the one-photon transparency for 0 to 1 transition and two-photon transparency for 0 to 2 transition. The results are explained by the Autler-Townes splitting induced by the control microwave. In addition, two possible microwave amplification processes involving two-photon processes are also studied. The 4-wave mixing scheme increases the transmission by 3% while 2-photon optical pumping produces a 11% narrowband increment. All these phenomena can be operated with control and probe tones in a narrow band.

A novel shaped-controlled fabrication of nanopore and its applications in quantum electronics.

High-intensity (107-108 A m-2) electron beams can be used to fabricate nanoscale pores. This approach enables real-time observation of nanopore drilling and precise control of the diameter of the nanopore. Nevertheless, it is not suitable for tuning the nanopore's sidewall shape. In this study, we demonstrate the use of low-intensity electron beams to fabricate nanopores on a silicon nitride (SiNx) membrane. This technique allows the precise adjustment of the nanopore dimension and the shaping of its three-dimensional (3D) nanostructure. The 3D structures of the nanopore were evaluated by electron tomography, and series of oblique images were used in reconstructing the 3D images of nanopores using a weighted back-projection method. The sidewall shape of the nanopore was observed at different electron-beam conditions, and the formation mechanism was elucidated based on these results. The nanopore fabricated with this technique can be used as a template to develop electronics at the nanoscale based on which a quantum-dot device can be prepared with a simple evaporation process. The measured results show that the device can resolve well-defined electronic states that are characteristic for the behaviors of the quantum-dot device.

Synthesis and Properties of Quinoxaline-Containing Benzoxazines and Polybenzoxazines.

The object of this work is to prepare quinoxaline-based benzoxazines and evaluate thermal properties of their thermosets. For this object, 4,4'-(quinoxaline-2,3-diyl)diphenol (QDP)/furfurylamine-based benzoxazine (QDP-fu) and 4,4',4″,4‴-([6,6'-biquinoxaline]-2,2',3,3'-tetrayl)tetraphenol (BQTP)/furfurylamine-based benzoxazine (BQTP-fu) were prepared. The structures of QDP-fu and BQTP-fu were successfully confirmed by FTIR and 1H and 13C NMR spectra. We studied the curing behavior of QDP-fu and BQTP-fu and thermal properties of their thermosets. According to DSC thermograms, QDP-fu and BQTP-fu have the attractive onset exothermic temperatures of 181 and 186 °C, respectively. The onset temperature is approximately 45 °C lower than that of a bisphenol A/furfurylamine-based benzoxazines. According to DMA TMA and TGA thermograms, the thermoset of BQTP-fu shows impressive thermal properties, with a T g value of 418 °C, a coefficient of thermal expansion of 39 ppm/°C, a 5% decomposition temperature of 430 °C, and a char yield of 72%.

Risk of joint replacement surgery in Taiwanese female adults with systemic lupus erythematosus: a population-based cohort study.

BACKGROUND: Female patients with systemic lupus erythematosus (SLE) are prone to have musculoskeletal system involvement, which could lead to joint damage. However, few studies have assessed the incidence of arthroplasty in female patients with SLE. The aim of this study was to investigate the risk of total hip replacement surgery and total knee replacement surgery in patients with SLE. METHODS: We identified 577 female patients with newly diagnosed SLE between 2000 and 2012 using the Taiwan's National Health Insurance Research Database. A comparison cohort was constructed with female patients without SLE in a ratio of 5:1, based on frequency matching for 10-year age interval, and index year, for each patient with SLE. Both cohorts were followed until a diagnosis of the study outcomes or the end of the follow-up period. RESULTS: Female patients with SLE showed a significantly higher incidence of receiving total hip replacement surgery (adjusted incidence rate ratio [aIRR] 6.47; P < 0.001), but not total knee replacement surgery (aIRR 1.81; P = 0.227). Moreover, age-group stratified analyses indicated a high incidence for receiving total hip replacement surgery among young female patients with SLE (aIRR 7.70; P = 0.001). CONCLUSION: Young female patients with SLE had a high risk of receiving total hip replacement surgery, but not total knee replacement surgery.

Sex-moderated interactions between IL4/IL13 pathway genes and prenatal environment on cord blood IgE levels.

BACKGROUND: Elevated cord blood IgE (cIgE), a predictor of atopic diseases, is influenced by genetic and environmental factors. However, gene-environment interactions on cIgE elevation and their difference by sex remain largely unexplored. OBJECTIVE: This study aimed to determine whether there are sex-moderated interactions between genetic variants in the IL4/IL13 pathway and prenatal environments on cIgE elevation. METHODS: Comprehensive information on environmental tobacco smoke (ETS), home dampness (indexed by combining mildewy odour, visible mould and water stamp on the wall) and other household environments was obtained using a structured questionnaire during the third trimester of pregnancy in 1107 full-term newborns. The cord blood was collected for measuring cIgE levels, with elevation defined as ≥0.5 IU/mL, and for genotyping of five single nucleotide polymorphisms of three candidate genes (IL-13 rs1800925, rs20541, rs848, IL-4 rs2243250 and STAT6 rs324011). RESULTS: Gene-environment interactions on cIgE elevation were observed in male but not female newborns, including those between ETS and IL13 rs20541, between home dampness and STAT6 rs324011, and between composite environmental exposure (combined ETS and the three home dampness indices) and STAT6 rs324011 (P for interaction = 0.03, 0.006, and 0.001, respectively). Male newborns carrying STAT6 rs324011 CT or TT genotype manifested with a significant dose-response association of the composite environmental exposure with cIgE elevation. CONCLUSION AND CLINICAL RELEVANCE: Sex moderates the gene-environment interactions involving IL4/IL13 pathway genes and prenatal household environments on cIgE elevation. The absence of prenatal exposure to ETS and home dampness in male neonates carrying the STAT6 rs324011 CT or TT genotype is least likely associated with cIgE elevation.

Efficient and Adhesiveless Metallization of Flexible Polyimide by Functional Grafting of Carboxylic Acid Groups.

Surface metallization of polyimide (PI) is the key process for the preparation of flexible printed circuit boards (FPCBs). To meet the miniaturization demand, the ultrathinness of FPCB by the removal of the intermediate adhesive layer is imperative. The common adhesiveless process relies on the surface activation of hydrophobic PI through alkaline hydrolysis to generate the hydrophilic carboxylate anion sites for the metallic deposition. However, the alkaline hydrolysis process involves the imide ring cleavage caused by the attack of a strong nucleophile (OH-), resulting in mechanical destruction and surface coarseness of PI. In this study, a new PI is synthesized with the grafting of carboxylic acid groups as the active sites to intrinsically activate PI for efficient metallization. The surface activation is accomplished through an acid-base neutralization reaction in a dilute alkaline environment, which can suppress the alkaline hydrolysis reaction. The attenuated total reflection Fourier transform infrared spectroscopy analysis confirms a significant reduction of the extent of the imide ring cleavage in the carboxylic acid-grafted PI films. According to the microstructural examination using transmission electron microscopy, the deposited metal film adheres firmly to the carboxylic acid-grafted PI films through an interlocking effect of a broccoli bud-shaped nanocluster layer.

Low-Dissipation Thermosets Derived from Oligo(2,6-Dimethyl Phenylene Oxide)-Containing Benzoxazines.

Poly(2,6-dimethyl phenyl oxide) (PPO) is known for its low dissipation factor. To achieve insulating materials with low dissipation factors for high-frequency communication applications, a telechelic oligomer-type benzoxazine (P-APPO) and a main-chain type benzoxazine polymer (BPA-APPO) were prepared from an amine end-capped oligo (2,6-dimethyl phenylene oxide) (APPO). The APPO was prepared from a nucleophilic substitution of a phenol-end capped oligo (2,6-dimethyl phenylene oxide) (a commercial product, SA 90) with fluoronitrobenzene, and followed by catalytic hydrogenation. After self-curing or curing with a dicyclopentadiene-phenol epoxy (HP 7200), thermosets with high-Tg and low-dissipation factor can be achieved. Furthermore, the resulting epoxy thermosets show better thermal and dielectric properties than those of epoxy thermoset cured from its precursor SA90, demonstrating it is a successful modification in simultaneously enhancing the thermal and dielectric properties.