Erythroid anion Exchanger-1 (band 3) transports nitrite for nitric oxide metabolism.

Nitrite (NO2-) interacts with hemoglobin (Hb) in various ways to regulate blood flow. During hypoxic vasodilation, nitrite is reduced by deoxyHb to yield nitric oxide (NO). While NO, a hydrophobic gas, could freely diffuse across the cell membrane, how the reactant nitrite anion could permeate through the red blood cell (RBC) membrane remains unclear. We hypothesized that Cl-/HCO3- anion exchanger-1 (AE1; band 3) abundantly embedded in the RBC membrane could transport NO2-, as HCO3- and NO2- exhibit similar hydrated radii. Here, we monitored NO/N2O3 generated from NO2- inside human RBCs by DAF-FM fluorophore. NO2-, not NO3-, increased intraerythrocytic DAF-FM fluorescence. To test the involvement of AE1-mediated transport in intraerythrocytic NO/N2O3 production from nitrite, we lowered Cl- or HCO3- in the RBC-incubating buffer by 20 % and indeed observed slower rise of the DAF-FM fluorescence. Anti-extracellular AE1, but not anti-intracellular AE1 antibodies, reduced the rates of NO formation from nitrite. The AE1 blocker DIDS similarly reduced the rates of NO/N2O3 production from nitrite in a dose-dependent fashion, confirming that nitrite entered RBCs through AE1. Nitrite inside the RBCs reacted with both deoxyHb and oxyHb, as evidenced by 6.1 % decrease in deoxyHb, 14.7 % decrease in oxyHb, and 20.7 % increase in methemoglobin (metHb). Lowering Cl- in the milieu equally delayed metHb production from nitrite-oxyHb and nitrite-deoxyHb reactions. Thus, AE1-mediated NO2- transport facilitates NO2--Hb reactions inside the red cells, supporting NOx metabolism in circulation.

Effects of greater erythroid Cl-/HCO3- transporter (band 3) expression on ventilation and gas exchange during exhaustive exercise.

Band 3 protein is a Cl-/[Formula: see text] transporter on the red blood cell (RBC) surface with an important role in CO2 excretion. Greater band 3 expression by roughly 20% is found in people with the GP.Mur blood type. Intriguingly, a disproportional percentage of those with GP.Mur excel in field-and-track sports. Could higher band 3 activity benefit an individual's physical performance? This study explored the impact of GP.Mur/higher band 3 expression on ventilation and gas exchange during exhaustive exercise. We recruited 36 nonsmoking, elite male athletes (36.1% GP.Mur) from top sports universities to perform incremental exhaustive treadmill cardiopulmonary exercise testing (CPET). We analyzed CPET data with respect to absolute running time and to individual's %running time and %maximal O2 uptake. We found persistently higher respiratory frequencies and slightly lower tidal volume in GP.Mur athletes, resulting in a slightly larger increase of ventilation as the workload intensified. The expiratory duty cycle (Te/Ttot) was persistently longer and inspiratory duty cycle (Ti/Ttot) was persistently shorter for GP.Mur subjects throughout the run. Consequently, end-tidal pressure of carbon dioxide ([Formula: see text], a surrogate marker for alveolar and arterial CO2 tension-[Formula: see text] and [Formula: see text]) was lower in the GP.Mur athletes during the early stages of exercise. In conclusion, athletes with GP.Mur and higher band 3 expression hyperventilate more during exercise in a pattern that uses a greater fraction of time for expiration than inspiration to increase the rate of CO2 excretion than increased tidal volume. This greater ventilation response reduced Pco2 and may help to extend exercise capacity in high-level sports.NEW & NOTEWORTHY Higher expression of the Cl-/[Formula: see text] transporter band 3 anion exchanger-1 (AE1) on the red blood cell membrane, as in people with the GP.Mur blood type, increases the rate of CO2 excretion during exercise.

In search of a better CPAP interface: A network meta-analysis comparing nasal masks, nasal pillows and oronasal masks.

Until now, no study has directly network meta-analysed the impact of nasal masks, nasal pillows and oronasal masks on continuous positive airway pressure therapy in patients with obstructive sleep apnea. This study aimed to meta-analyse the impact of three kinds of nasal interfaces with both network meta-analysis and pairwise comparison. PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were systematically searched from inception to December 2020 for studies that compared the three types of nasal interfaces for treating obstructive sleep apnea with continuous positive airway pressure. The outcomes were residual apnea-hypopnea index, continuous positive airway pressure, and nightly average usage. The network meta-analysis was conducted using multivariate random-effects in a frequentist framework where three interfaces were ranked with the surface under the cumulative ranking probabilities. The pairwise comparison was conducted using random-effects meta-analysis. Twenty-nine articles comprising 6378 participants were included. The pairwise comparison showed both nasal masks and nasal pillows were associated with lower residual apnea-hypopnea index, lower continuous positive airway pressure, and higher continuous positive airway pressure adherence compared with oronasal masks. The surface under the cumulative ranking confirmed that nasal masks were associated with the lowest residual apnea-hypopnea index and highest adherence, while pillows were associated with the lowest continuous positive airway pressure. The meta-regression identified that lower pretreatment apnea-hypopnea index and continuous positive airway pressure determined during continuous positive airway pressure titration (versus determined during continuous positive airway pressure therapy) was associated with lower continuous positive airway pressure with nasal masks and nasal pillows. In conclusion, compared with oronasal masks, nasal masks and nasal pillows are better interfaces, especially in patients with lower pretreatment apnea-hypopnea index and those with the therapeutic pressure determined during continuous positive airway pressure titration.

Influence of hemoglobin on blood pressure among people with GP.Mur blood type☆.

BACKGROUND/PURPOSE: GP.Mur is a clinically important red blood cell (RBC) type. GP.Mur and band 3 interact on the RBCs. We previously observed that healthy adults with GP.Mur type present slightly higher blood pressure (BP). Because band 3 and Hb comodulate nitric oxide (NO)-dependent vasodilation and hemoglobin (Hb) is positively associated with BP, we aimed to test whether these could contribute to higher BP in GP.Mur+ people. METHODS: We recruited 989 non-elderly adults (21% GP.Mur) free of catastrophic illness and not on cardiovascular or anti-hypertensive medication. Their body indices, blood lab data and lifestyle data were collected for analyses of potential BP-related factors (BMI, age, smoking, Hb, and GP.Mur). RESULTS: BMI and age remained the most significant contributors to BP. GP.Mur slightly increased systolic BP (SBP). The direct correlation between Hb and BP was only found in Taiwanese non-anemic men, not women. After age and BMI adjusted, we estimated an increase of 1.8 mmHg and 2.6 mmHg of SBP by 1 g/dL Hb among men without and with GP.Mur type, respectively. Hb was generally lower among people expressing GP.Mur, which likely limited their larger impact on BP. CONCLUSION: GP.Mur contributed to BP in both Hb-dependent and Hb-independent fashion. A pronounced impact of hemoglobin on BP likely requires sufficient Hb, as GP.Mur increased the sensitivity of SBP to Hb only in non-anemic Taiwanese men, and not in Taiwanese women or anemic men. The mechanism through which GP.Mur affected BP independent of Hb is unknown.

Comodulation of NO-Dependent Vasodilation by Erythroid Band 3 and Hemoglobin: A GP.Mur Athlete Study.

GP.Mur, a red blood cell (RBC) hybrid protein encoded by glycophorin B-A-B, increases expression of erythroid band 3 (Anion Exchanger-1, SLC4A1). GP.Mur is extremely rare but has a prevalence of 1-10% in regions of Southeast Asia. We unexpectedly found slightly higher blood pressure (BP) among healthy Taiwanese adults with GP.Mur. Since band 3 has been suggested to interact with hemoglobin (Hb) to modulate nitric oxide (NO)-dependent hypoxic vasodilation during the respiratory cycle, we hypothesized that GP.Mur red cells could exert differentiable effects on vascular tone. Here we recruited GP.Mur-positive and GP.Mur-negative elite male college athletes, as well as age-matched, GP.Mur-negative non-athletes, for NO-dependent flow-mediated dilation (FMD) and NO-independent dilation (NID). The subjects were also tested for plasma nitrite and nitrate before and after arterial occlusion in FMD. GP.Mur+ and non-GP.Mur athletes exhibited similar heart rates and blood pressure, but GP.Mur+ athletes showed significantly lower FMD (4.8 ± 2.4%) than non-GP.Mur athletes (6.5 ± 2.1%). NO-independent vasodilation was not affected by GP.Mur. As Hb controls intravascular NO bioavailability, we examined the effect of Hb on limiting FMD and found it to be significantly stronger in GP.Mur+ subjects. Biochemically, plasma nitrite levels were directly proportional to individual band 3 expression on the red cell membrane. The increase of plasma nitrite triggered by arterial occlusion also showed small dependency on band 3 levels in non-GP.Mur subjects. By the GP.Mur comparative study, we unveiled comodulation of NO-dependent vasodilation by band 3 and Hb, and verified the long-pending role of erythroid band 3 in this process.

Diagnosis of mediastinal tuberculous lymphadenitis using endobronchial ultrasound-guided transbronchial needle aspiration with rinse fluid polymerase chain reaction.

BACKGROUND/PURPOSE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been gradually introduced in the diagnosis of mediastinal tuberculous (TB) lymphadenitis. The purposes of this study were to evaluate the utility of polymerase chain reaction for Mycobacterium tuberculosis (TB-PCR) using EBUS-TBNA rinse fluid and to explore the factors that influence the accuracy of EBUS-TBNA. METHODS: A retrospective study with prospective data collection was carried out with patients with unselected mediastinal lymphadenopathy who underwent EBUS-TBNA and a TB-PCR study from April 2010 to July 2017. Patients without TB were excluded. The diagnostic accuracy rate for each diagnostic modality (pathology, smear, culture, and TB-PCR) was calculated respectively. The characteristics of the lymph node (LN) and the pathologic findings were analyzed as possible impact factors. RESULTS: 240 consecutive patients who received EBUS-TBNA were enrolled, and in the end, 21 patients with a diagnosis of TB lymphadenitis were included. When combined with histologic results and traditional microbiologic studies, the diagnostic accuracy of EBUS-TBNA was 57.1%. If TB-PCR was also utilized, the diagnostic accuracy would significantly increase to 71.4% (p < 0.001). Univariate and multivariate regression analysis revealed that pathology showing necrosis had a higher positive microbiologic result when using EBUS-TBNA rinse fluid. CONCLUSION: EBUS-TBNA is a valuable tool for diagnosis of mediastinal TB lymphadenitis. Using TB-PCR assay and targeting LNs with a necrotic component would improve the diagnostic performance of EBUS-TBNA.

Ribose-5-phosphate isomerase A overexpression promotes liver cancer development in transgenic zebrafish via activation of ERK and ß-catenin pathways.

Dysregulation of the enzymes involved in the pentose phosphate pathway (PPP) is known to promote tumorigenesis. Our recent study demonstrated that ribose-5-phosphate isomerase (RPIA), a key regulator of the PPP, regulates hepatoma cell proliferation and colony formation. Our studies in zebrafish reveal that RPIA-mediated hepatocarcinogenesis requires extracellular signal-regulated kinase (ERK) and ß-catenin signaling. To further investigate RPIA-mediated hepatocarcinogenesis, two independent lines of transgenic zebrafish expressing human RPIA in the liver were generated. These studies reveal that RPIA overexpression triggers lipogenic factor/enzyme expression, steatosis, fibrosis and proliferation of the liver. In addition, the severity of fibrosis and the extent of proliferation are positively correlated with RPIA expression levels. Furthermore, RPIA-mediated induction of hepatocellular carcinoma (HCC) requires the ERK and ß-catenin signaling pathway but is not dependent upon transaldolase levels. Our study presents a mechanism for RPIA-mediated hepatocarcinogenesis and suggests that RPIA represents a valuable therapeutic target for the treatment of HCC.

Transfection of the IHH gene into rabbit BMSCs in a simulated microgravity environment promotes chondrogenic differentiation and inhibits cartilage aging.

The effect of overexpressing the Indian hedgehog (IHH) gene on the chondrogenic differentiation of rabbit bone marrow-derived mesenchymal stem cells (BMSCs) was investigated in a simulated microgravity environment. An adenovirus plasmid encoding the rabbit IHH gene was constructed in vitro and transfected into rabbit BMSCs. Two large groups were used: conventional cell culture and induction model group and simulated microgravity environment group. Each large group was further divided into blank control group, GFP transfection group, and IHH transfection group. During differentiation induction, the expression levels of cartilage-related and cartilage hypertrophy-related genes and proteins in each group were determined. In the conventional model, the IHH transfection group expressed high levels of cartilage-related factors (Coll2 and ANCN) at the early stage of differentiation induction and expressed high levels of cartilage hypertrophy-related factors (Coll10, annexin 5, and ALP) at the late stage. Under the simulated microgravity environment, the IHH transfection group expressed high levels of cartilage-related factors and low levels of cartilage hypertrophy-related factors at all stages of differentiation induction. Under the simulated microgravity environment, transfection of the IHH gene into BMSCs effectively promoted the generation of cartilage and inhibited cartilage aging and osteogenesis. Therefore, this technique is suitable for cartilage tissue engineering.

Coexistence of EGFR T790M mutation and common activating mutations in pretreatment non-small cell lung cancer: A systematic review and meta-analysis.

OBJECTIVE: Previous studies have indicated that EGFR exon 19 deletions in non-small cell lung cancer (NSCLC) are associated with better outcomes to tyrosine kinase inhibitors (TKIs) than the L858R mutation. This study aimed to evaluate whether T790M, a resistant mutation, is more likely to coexist with L858R mutation than with exon 19 deletions in pretreatment NSCLC patients. MATERIALS AND METHOD: We searched MEDLINE and EMBASE up to Nov 30th, 2015 to identify randomized controlled trials (RCTs) and observational studies that reported pretreatment T790M and EGFR-activating mutation. A meta-analysis was performed using a random-effects model. The primary outcome was odds ratio (OR) of pretreatment T790M mutation in NSCLC co-existing with L858R mutation and exon 19 deletions. Stratified analysis was performed based on sensitivity of mutation detection methods for T790M. RESULTS: We identified 15 observational studies and 3 RCTs for analysis. Pretreatment T790M was more frequent in L858R than in exon 19 mutated patients. The association of T790M and L858R was statistically significant in observational studies (OR, 1.65, 95% CI, 1.17-2.32), with less precision in RCTs (OR, 1.84, 95% CI, 0.96-3.52). In the stratified analysis based on the sensitivity of the mutation detection methods, the association was observed in the studies using intermediately (detection limit <5% and ≥ 0.1%; OR, 2.23, 95% CI, 1.19-4.17) and highly sensitive methods (detection limit <0.1%; OR, 1.74, 95% CI, 1.10-2.73), but not in those using low sensitivity methods (detection limit >5%; OR, 1.28, 95% CI, 0.74-2.23). CONCLUSIONS: Pretreatment EGFR T790M mutation is more likely to coexist with L858R mutation than with exon 19 deletions in NSCLC. This association was observed only in studies using sensitive mutation detection methods (<5%).

Protection against Klebsiella pneumoniae using lithium chloride in an intragastric infection model.

Intragastric Klebsiella pneumoniae infections of mice can cause liver abscesses, necrosis of liver tissues, and bacteremia. Lithium chloride, a widely prescribed drug for bipolar mood disorder, has been reported to possess anti-inflammatory properties. Using an intragastric infection model, the effects of LiCl on K. pneumoniae infections were examined. Providing mice with drinking water containing LiCl immediately after infection protected them from K. pneumoniae-induced death and liver injuries, such as necrosis of liver tissues, as well as increasing blood levels of aspartate aminotransferase and alanine aminotransferase, in a dose-dependent manner. LiCl administered as late as 24 h postinfection still provided protection. Monitoring of the LiCl concentrations in the sera of K. pneumoniae-infected mice showed that approximately 0.33 mM LiCl was the most effective dose for protecting mice against infections, which is lower than the clinically toxic dose of LiCl. Surveys of bacterial counts and cytokine expression levels in LiCl-treated mice revealed that both were effectively inhibited in blood and liver tissues. Using in vitro assays, we found that LiCl (5 µM to 1 mM) did not directly interfere with the growth of K. pneumoniae but made K. pneumoniae cells lose the mucoid phenotype and become more susceptible to macrophage killing. Furthermore, low doses of LiCl also partially enhanced the bactericidal activity of macrophages. Taken together, these data suggest that LiCl is an alternative therapeutic agent for K. pneumoniae-induced liver infections.

Adaptive filter design using recurrent cerebellar model articulation controller.

A novel adaptive filter is proposed using a recurrent cerebellar-model-articulation-controller (CMAC). The proposed locally recurrent globally feedforward recurrent CMAC (RCMAC) has favorable properties of small size, good generalization, rapid learning, and dynamic response, thus it is more suitable for high-speed signal processing. To provide fast training, an efficient parameter learning algorithm based on the normalized gradient descent method is presented, in which the learning rates are on-line adapted. Then the Lyapunov function is utilized to derive the conditions of the adaptive learning rates, so the stability of the filtering error can be guaranteed. To demonstrate the performance of the proposed adaptive RCMAC filter, it is applied to a nonlinear channel equalization system and an adaptive noise cancelation system. The advantages of the proposed filter over other adaptive filters are verified through simulations.

Performance investigation of GaN-based light-emitting diodes with tiny misorientation of sapphire substrates.

GaN-based light-emitting diodes (LEDs) grown on c-plane vicinal sapphire substrates are fabricated and characterized. Based on the material quality and electrical properties, the LED with a 0.2 degrees tilt sapphire substrate (device A) exhibits the lowest defect density and high performance, while the LED with a 1.0 degrees tilt sapphire (device D) exhibits the highest one. At 2 mA, the extremely enhanced output power of 23.3% indicates of the reduction of defect-related nonradiative recombination centers in active layers for the device A. At 60 mA, the improved value is up to 45.7%. This is primarily caused by the formation of indium quantum dots in MQW which provides an increased quantum efficiency.

[Study on stabilized hyaluronic acid-based gel of non-animal origin for the correction of nasolabial folds].

OBJECTIVE: To assess the safety and efficacy of hyaluronic acid-based gel of non-animal origin (NASHA gel [Restylane]; Q-Med AB, Uppsala, Sweden)for correcting nasolabial folds in Chinese. METHODS: Patients with moderate or severe nasolabial fold (Wrinkle Severity Rating Scale, WSRS) were recruited to receive NASHA gel injection ( < 1.5 ml). The patients were followed up for 6 months. The efficacy was assessed by physicians and patients, respectively. Adverse events (AEs) were recorded and laboratory tests were performed before and after operation. RESULTS: 86 patients were treated. 6 months after injection, improved esthetic results was assessed by patients and physicians independently. 52 AEs happened in 32 cases (37.2%). Most of them were local injection reaction and minor, which were recovered spontaneously. No systemic reaction was found. CONCLUSIONS: NASHA gel can improve the nasolabial folds. It is very safe and tolerated.

RCMAC hybrid control for MIMO uncertain nonlinear systems using sliding-mode technology.

A hybrid control system, integrating principal and compensation controllers, is developed for multiple-input-multiple-output (MIMO) uncertain nonlinear systems. This hybrid control system is based on sliding-mode technique and uses a recurrent cerebellar model articulation controller (RCMAC) as an uncertainty observer. The principal controller containing an RCMAC uncertainty observer is the main controller, and the compensation controller is a compensator for the approximation error of the system uncertainty. In addition, in order to relax the requirement of approximation error bound, an estimation law is derived to estimate the error bound. The Taylor linearization technique is employed to increase the learning ability of RCMAC and the adaptive laws of the control system are derived based on Lyapunov stability theorem and Barbalat's lemma so that the asymptotical stability of the system can be guaranteed. Finally, the proposed design method is applied to control a biped robot. Simulation results demonstrate the effectiveness of the proposed control scheme for the MIMO uncertain nonlinear system.