MiR-4454 in Combined Allergic Rhinitis and Asthma Syndrome (CARAS): Clinical significance and mechanistic insights into airway inflammation.

Abnormal expression of non-coding microRNA is associated with the development of combined allergic rhinitis and asthma syndrome (CARAS). However, the function of miR-4454 in CARAS is unknown. Our study aimed to reveal the clinical significance and related mechanism of miR-4454 in CARAS. Blood samples from 38 cases of CARAS and 43 cases of healthy subjects were collected to detect the expression of miR-4454. House dust mite (HDM) sensitization and challenge-induced bronchial epithelial cells to simulate the asthma state model in vitro, miR-4454 mimics and inhibitor transfection to detect the expression level of pro-inflammatory cytokines, cell survival rate and migration ability, flow cytometry and western blot (WB) Detection of cell cycle, apoptosis and inflammation-related protein levels. Compared with healthy controls, the expression of miR-4454 in the blood of CARAS patients was significantly up-regulated, and IL-6 and IL-8 were significantly up-regulated in the HDM treatment group, indicating that the model induction was successful. After overexpression of miR-4454, cell proliferation and migration in the HDM-treated group were significantly inhibited, and the levels of early apoptosis and inflammation-related proteins (IL-17, IL-17RD, TNF-α, GCSF and NF-κB) were increased High; after inhibiting miR-4454, cell proliferation and migration were significantly enhanced, and the levels of apoptosis and inflammation-related proteins were decreased. This study found that inhibiting the expression of miR-4454 can improve HDM-induced cell injury, which may be related to miR-4454 regulating the activation of IL-17/NF-кB inflammatory axis.

Ligand-of-Numb protein X1 controls the coxsackievirus B3-induced myocarditis via regulating the stability of coxsackievirus and adenovirus receptor.

Group B coxsackieviruses (CVBs) are the main cause of virus-induced myocarditis. CVBs use coxsackievirus and adenovirus receptor (CAR) for infection and targeting CAR has been shown to ameliorate CVBs-induced myocarditis. Ligand-of-Numb protein X1 (LNX1) is an E3 ubiquitin ligase that was shown to interact with CAR. However, the precise effect of LNX1 on CAR and the roles of LNX1 on CVBs-induced myocarditis remain unknown. In the present study, we generated mice deficient in LNX1 in the heart and evaluated the symptoms of myocarditis after CVB3 infection. We also monitored the expression and ubiquitination of CAR in LNX1-deficient cardiomyocytes after CVBs infection. We found that CVBs infection decreased CAR expression while promoted the expression of LNX1. Mice with deficiency of LNX1 in the heart had normal myocardial development while had deteriorated myocarditis symptoms after CVB3 infection. In LNX1-deficient cardiomyocytes, decreased ubiquitination of CAR and upregulation of CAR were observed after CVB3 infection. In summary, LNX1 controls CVB3-induced myocarditis by regulating the expression of CAR.

Vertical diversity and association pattern of total, abundant and rare microbial communities in deep-sea sediments.

Microbial abundance and community composition in marine sediments have been widely explored. However, high-resolution vertical changes of benthic microbial diversity and co-occurrence patterns are poorly described. The ecological contributions of abundant and rare species in sediments also remain largely unknown. Here, by analysing microbial populations at 14 depth layers of 10 subseafloor sediment cores (water depth 1,250-3,530 m) obtained in the South China Sea, we provided the vertical profiles of microbial ß-diversity and co-occurrence influenced by subcommunities of different abundance. These 134 sediment samples were clustered into four groups according to sediment depth (1-2, 6-10, 30-90 and 190-790 cm) with obvious shifts in microbial community compositions. The vertical succession of microorganisms was consistent with redox zonation and influenced by terrestrial inputs. Partitioning of vertical ß-diversity showed extremely high species replacement between deep layers and the surface layer, indicating selection-induced loss of rare species and dispersal of dormant cells and spores. By contrast, for horizontal ß-diversity, richness of rare species became increasingly significant in deep sediments. Accompanying this ß-diversity profile were clear changes in the association pattern, with microorganisms being less connected in deeper sediment layers, probably reflecting reduced syntrophic interactions. Rare species accounted for an indispensable proportion in the co-occurrence network, and tended to form complex "small worlds." The rare subcommunity also responded differently to various environmental factors compared with the abundant subcommunity. Our findings expand current knowledge on vertical changes of marine benthic microbial diversity and their association patterns, emphasizing the potential roles of rare species.

Simulation of stray radiation from optical window with temperature-dependent spectral properties.

Stray radiation analysis coupled with a temperature field is performed for a semitransparent window, focusing on the temperature-dependent optical properties. The transient temperature response of the optical window-based encapsulation structure is first investigated under an external transient high-heat flux loading. The spectral selectivity of the window to thermal radiation is involved. Subsequently, several typical cases for stray radiation are conducted, considering the inhomogeneous optical properties caused by the temperature heterogeneity. It is found that the stray radiation distribution is more chaotic compared to the results with optical properties independent of temperature. In addition, the stray radiation power has a large deviation (150%) if one neglects the temperature dependence. Meanwhile, the difference in wave band power decreases with the wavelength rising. Additionally, the stray radiation power generated by the window is far less in the visible wave band than that in the near-infrared wave band. The results reveal that the temperature dependence in optical properties of a semitransparent window should be seriously considered when calculating the stray radiation, especially in high-precision detection devices.

Sirt6 stabilizes atherosclerosis plaques by promoting macrophage autophagy and reducing contact with endothelial cells.

Sirt6 has been reported to play a protective role in macrophage foam cell formation, but whether Sirt6 controls atherosclerosis plaque stability and whether it can reduce the interaction between endothelial cells and macrophages remains unclear. The aim of this study was to investigate the effect of Sirt6 on atherosclerosis plaque stability and the underlying mechanisms. We used Tie2-Cre transgenic mice as a Cre-lox tool to delete Sirt6 floxed sequences in endothelial cells during adulthood to establish Sirt6-/- mice. ApoE-/-:Sirt6-/- and ApoE-/-:Sirt6Tg mice were used in our investigation. After a 16 week high-fat diet, the mice developed markedly atherosclerotic plaques. Sirt6 knockout exacerbated atherosclerotic plaque progression in both size and stability. In vitro, murine macrophage RAW264.7 cells were treated with ox-low density lipoproteins for 24 h to simulate atherosclerosis. Furthermore, Sirt6 overexpression remarkably increased autophagic flux in macrophages and inhibited macrophage apoptosis. Moreover, Sirt6 overexpression inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and platelet selectin (P-selectin), leading to reduced infiltration of macrophages and foam cells. In conclusion, our study indicates a new mechanism-based strategy to therapeutically stimulate atherosclerosis plaque stability.

Simultaneous measurement of displacement, pitch, and yaw angles of a cavity output mirror based on phase measuring deflectometry.

Accurate and high dynamic range measurement of the three attitude variations (i.e., displacement, pitch, yaw angles) has been widely researched based on various approaches to meet different application requirements. However, none of the existing methods can detect these three attitude variations at the same time. This paper proposes a method based on a classical phase measuring deflectometry (PMD) system and a double iteration algorithm to simultaneously measure the three variations of the output mirror in a laser resonator. The relationship between the attitude variations and the lateral displacement parameters (LDP) of the imaged structural fringes is derived in the PMD system. Through the established relationship, the attitude variations could be calculated once the LDP are detected. Furthermore, a two-step measuring scheme combining the four-step shifting phase and the color-coded fringe is proposed to effectively detect the LDP. Finally, an experiment is conducted to verify the feasibility of the proposed method.

Deformable mirror resolution-matching-based two-stage wavefront sensorless adaptive optics method.

In high-power laser facilities, the application of a traditional wavefront control method is limited under the influence of a continuous phase plate (CPP). In order to obtain a satisfactory far-field intensity distribution at the target of the beamline with the CPP, a novel deformable mirror (DM) resolution-matching-based two-stage wavefront sensorless adaptive optics method is proposed and demonstrated. The principles of the DM resolution-matching method and two-stage wavefront sensorless adaptive optics method are introduced, respectively. Based on the numerical model, the matching relationship between the actuator space of the DM and the spatial period of the CPP is investigated. By using the resolution-matched DM, the feasibility of the two-stage wavefront sensorless adaptive optics method is numerically and experimentally verified. Both the numerical and the experimental results show that the presented DM resolution-matching-based two-stage wavefront sensorless adaptive optics method could achieve the target focal spot control under the influence of the CPP, and the profile and the intensity uniformity of the corrected focal spot are optimized close to the designed ideal focal spot.

Smad7 enables STAT3 activation and promotes pluripotency independent of TGF-ß signaling.

Smad7 is a negative feedback product of TGF-ß superfamily signaling and fine tunes a plethora of pleiotropic responses induced by TGF-ß ligands. However, its noncanonical functions independent of TGF-ß signaling remain to be elucidated. Here, we show that Smad7 activates signal transducers and activators of transcription 3 (STAT3) signaling in maintaining mouse embryonic stem cell pluripotency in a manner independent of the TGF-ß receptors, yet dependent on the leukemia inhibitory factor (LIF) coreceptor glycoprotein 130 (gp130). Smad7 directly binds to the intracellular domain of gp130 and disrupts the SHP2-gp130 or SOCS3-gp130 complex, thereby amplifying STAT3 activation. Consequently, Smad7 facilitates LIF-mediated self-renewal of mouse ESCs and is also critical for induced pluripotent stem cell reprogramming. This finding illustrates an uncovered role of the Smad7-STAT3 interplay in maintaining cell pluripotency and also implicates a mechanism involving Smad7 underlying cytokine-dependent regulation of cancer and inflammation.

Simulational and experimental investigation on the print-through high-frequency aberration of the shear-joint NIF deformable mirror.

A shear-joint deformable mirror (DM) is important in the high-power laser systems such as the National Ignition Facility (NIF). In this paper, the print-through high-frequency aberration (PT-HIFA) that arises from adhesive curing and is corresponding to the actuator array is reported to exist in the initial surface shape of a lab-made shear-joint NIF DM. Meanwhile, experimental results show that the PT-HIFA has a great modulation on the laser intensity. This PT-HIFA could not be corrected effectively by the DM and may result in dangerous damage in the high power laser systems. In order to eliminate the PT-HIFA, we investigate the influence of the structural parameters on the PT-HIFA in a shear-joint DM through simulation and experiment. Simulational results show that the structural parameters have different influences on the PT-HIFA. In the experiment, by optimizing the structural parameters, the PT-HIFA could be eliminated in the shear-joint NIF DM and the modulation effect on the laser intensity could be removed. This investigation could help other researchers to determine appropriate structural parameters and to achieve a fine surface shape in their own shear-joint DMs.

Theoretical research on the novel adaptive optics configuration based on the tubular deformable mirror for the aberration correction of the annular laser beam.

The annular laser beam (ALB) has been widely used in many fields for its unique intensity distribution. Especially, in the materials processing, the power and the beam quality of the large-aperture thin-wall ALB are of vital. However, limited by the aperture, the actuators' spacing or the damage threshold, the existing deformable mirrors (DMs) are not suitable for the correction of the ALB. Considering the stretching effect of the oblique incidence, in this paper, by using the tubular DM (TDM), a novel adaptive optics (AO) configuration is promoted to increase the number of the effective actuators covered by the input ALB. The coordinate transformation equations and correction principle of the novel AO configuration are derived based on the ray tracing. A typical TDM prototype is designed based on the coordinate transformation equations. The influence function characteristics of the TDM is analyzed using the finite element method, and the correction ability of the novel AO configuration based on the TDM is verified. Simulation results show that the TDM could perfectly compensate the wavefront distortions described by the 2th to 15th order Zernike annular aberrations.

High precision wavefront correction using an influence function optimization method based on a hybrid adaptive optics system.

A hybrid adaptive optics (AO) system with an influence function (IF) optimization method is presented for high precision wavefront correction of a traditional Shack-Hartmann AO system. The hybrid AO system consists of a Shack-Hartmann wavefront sensor (SHWFS) and a deflectometry system (DS) to measure the wavefront of the laser beam and the IF of the deformable mirror, respectively. An IF optimization method is used to generate a hybrid IF (H-IF) through a position-calibration algorithm and a resolution-conversion algorithm by use of the original IFs measured by the SHWFS (S-IF) and the DS (D-IF). Configuration of the hybrid AO system is introduced. Principles and calculation results of the IF optimization method are presented. Comparison of the wavefront correction ability between the H-IF and the original IF is carried out in simulation. Closed-loop performance of the hybrid AO system using the H-IF is investigated in experiment. Simulation and experiment results show that for a traditional Shack-Hartmann AO system, the H-IF has better correction ability than the original S-IF and the IF optimization method could help improve closed-loop performance without sacrificing the simplicity of the system structure and the rapidity of the closed-loop correction.

Numerical analysis of a novel two-stage enlargement and adaptive correction approach for the annular aberration compensation.

The annular laser beam (ALB) is widely used in many fields, which could be affected by laser power and beam quality. To effectively and flexibly improve the beam quality of high-power large-aperture thin-wall ALB, a two-stage enlargement and adaptive correction configuration (TEACC) consisting of a novel outer-surface tubular deformable mirror (OTDM) and two extra prism groups (EPGs) is proposed in this paper. The correction principle and design principle of the TEACC are derived and analyzed. Based on the principle, a typical OTDM prototype and EPG structure are designed. Annular aberrations are compensated by applying the OTDM's influence functions and the least-square algorithm in simulation. The results show that the TEACC could perfectly compensate the wavefront distortions described by the 2nd to 36th order Zernike annular aberrations.

Nicorandil alleviates myocardial injury and post-infarction cardiac remodeling by inhibiting Mst1.

BACKGROUND: Cardiomyocyte autophagy and apoptosis are crucial events underlying the development of cardiac abnormalities and dysfunction after myocardial infarction (MI). A better understanding of the cell signaling pathways involved in cardiac remodeling may support the development of new therapeutic strategies for the treatment of heart failure (HF) after MI. METHODS: A cardiac MI injury model was constructed by ligating the left anterior descending (LAD) coronary artery. Neonatal cardiomyocytes were isolated and cultured to investigate the mechanisms underlying the protective effects of nicorandil on MI-induced injury. RESULTS: Nicorandil reduced cardiac enzyme release, mitigated left ventricular enlargement and cardiac dysfunction after MI, as evaluated by echocardiography and hemodynamic measurements. According to the results of the western blot analysis and immunofluorescence staining, nicorandil enhanced autophagic flux and reduced apoptosis in cardiomyocytes subjected to hypoxic injury. Interestingly, nicorandil increased Mst1 and p-Mst1 levels in cardiomyocytes subjected to MI injury. Mst1 knockout abolished the protective effects of nicorandil on cardiac remodeling and dysfunction after MI. Mst1 knockout also abolished the beneficial effects of nicorandil on cardiac enzyme release and cardiomyocyte autophagy and apoptosis. CONCLUSIONS: Nicorandil alleviates post-MI cardiac dysfunction and remodeling. The mechanisms were associated with enhancing autophagy and inhibiting apoptosis through Mst1 inhibition.

Utilizing cell-based therapeutics to overcome immune evasion in hematologic malignancies.

Hematologic malignancies provide a suitable testing environment for cell-based immunotherapies, which were pioneered by the development of allogeneic hematopoietic stem cell transplant. All types of cell-based therapies, from donor lymphocyte infusion to dendritic cell vaccines, and adoptive transfer of tumor-specific cytotoxic T cells and natural killer cells, have been clinically translated for hematologic malignancies. The recent success of chimeric antigen receptor-modified T lymphocytes in B-cell malignancies has stimulated the development of this approach toward other hematologic tumors. Similarly, the remarkable activity of checkpoint inhibitors as single agents has created enthusiasm for potential combinations with other cell-based immune therapies. However, tumor cells continuously develop various strategies to evade their immune-mediated elimination. Meanwhile, the recruitment of immunosuppressive cells and the release of inhibitory factors contribute to the development of a tumor microenvironment that hampers the initiation of effective immune responses or blocks the functions of immune effector cells. Understanding how tumor cells escape from immune attack and favor immunosuppression is essential for the improvement of immune cell-based therapies and the development of rational combination approaches.

Simulational and experimental investigation on the actuator-corresponding high-frequency aberration of the piezoelectric stacked array deformable mirror.

The high-frequency aberrations (HIFAs) that are corresponding to the actuator array have been reported to exist on the initial surface shape of many deformable mirrors (DMs), such as the bimorph DM, the unimorph DM, the monomorph DM, and the membrane DM. This actuator-corresponding high-frequency aberration (AC-HIFA) could not be corrected effectively by the DM and would limit the correction ability of the DM. In this paper, we presented the AC-HIFA in a stacked array piezoelectric (PZT) DM, which may result in ghost damage that is dangerous in the high power laser system. More importantly, we investigated a solution through simulation and experiment that by using a mirror plate and a long thin post array, which were machined integrally from a piece of BK7 glass, the AC-HIFA could be eliminated completely. In addition, the structural parameters' influences on the AC-HIFA were investigated in the simulation, which could help other researchers to determine appropriate parameters of the mirror and the posts and to make a fine surface shape in their own DMs.

Theoretical and experimental research on temperature-induced surface distortion of deformable mirror.

In a well-manufactured deformable mirror (DM), the temperature-induced distortion (TID) has been reported exist on the surface shape of the DM, when the working environment temperature is not equal to that of the manufacturing environment. The DM could not effectively correct this actuator-corresponding TID and the correction ability of the DM would be limited. In this paper, the the TID's essential mechanism is analyzed systematically based on the thermal stress characteristics. An efficient method based on an auxiliary temperature compensation module (TCM) and a hybrid closed-loop control algorithm are presented accordingly. A finite element model is built to evaluate the TID characteristics and the compensation capability of the TCM. In the simulation, by using the TCM, the the DM's improved surface shape does not contain the dynamic high-frequency distortion caused by the actuators tilt. In the experiment, which uses a designed TCM and a hybrid closed-loop control algorithm, a DM's TID is effectively depressed and a well-compensated DM surface shape is finally achieved.

Intracavity deformable mirror for beam quality improvement and power enhancement of a passively Q-switched laser.

The performance of the passively Q-switched (PQS) laser deteriorates under high pumping power for the intracavity thermally induced wavefront distortion (thermal distortion for short). A new intracavity deformable mirror (DM) is proposed to compensate the thermal distortion of a PQS laser in this paper. The thermal distortion of the PQS laser is measured using the active deflectometry method. A simulation model is built to investigate the influences of the DM structure parameters on the surface shape of the DM (DMSS). Simulation results indicate that the DMSS matches well with the measured thermal distortion in the PQS laser at the given pumping current. Based on the simulation results, a low-cost, compact intracavity DM consisting of a mirror unit, a heater unit, a cooler unit and a base unit is built and used in the PQS laser. The DMSS is measured by a Zygo interferometer and coincides with the simulation result. In the improved PQS laser experiment, the optimum heater temperatures for the maximum output power and minimum M2 at different pumping currents are measured and given. The output stability of the PQS laser with the DM is tested. By adjusting the heater temperature, the PQS laser could achieve optimum performance in different environmental temperatures with good temperature adaptability. Experiment results verify that the PQS laser with the designed DM could achieve high output power and good beam quality at high pumping currents, as the DM prominently compensates the thermal distortion in the laser.

10.8 kW, 2.6 times diffraction limited laser based on a continuous wave Nd:YAG oscillator and an extra-cavity adaptive optics system.

In this Letter, a 10.8 kW, 2.6 times diffraction limited laser based on a continuous wave (CW) Nd:YAG oscillator using an unstable resonator and an extra-cavity adaptive optics system was presented. Two Nd:YAG slabs and a disk-laser configuration were used to make the laser compact and power scalable. The output was a rectangular annulus, which was further expanded to a square annulus and was adaptively corrected by an extra-cavity deformable mirror (DM). The DM was designed to be capable of correcting the square annular wavefront aberrations. In the experiment, the vertical beam quality was improved from 51.7 to 2.6 times diffraction limited after correction. To the best of our knowledge, this is the highest power and brightness based on a CW Nd:YAG oscillator.

High-accuracy measurement of the focal length and distortion of optical systems based on interferometry.

A figure measuring interferometer (FMI) method is proposed for high-accuracy measurement of the focal length and distortion of optical systems simultaneously. FMI uses the Zernike coefficients of interference fringe to identify the image point position precisely, and then measures the distance between the image points under the different fields to determine the image height. The field of view can also be accurately obtained by a precise rotating platform. Linear fitting between the field of view and the image height is used to calculate the focal length and distortion. The experimental results indicate that FMI has a relative expanded standard uncertainty of less than 0.01% for focal length and 0.02% for distortion. In brief, the proposed method is feasible for measurement of the focal length and distortion with high accuracy, promising further industrial applications.

[Effects of P and K fertilizer on content of coumarin and yield of Glehnia littoralis].

By a orthogonal experiment, the influence of different ratio of phosphorus and potassium fertilizers on imperatorin, isoimperatorin and psoralen contents and yield of Glehnia littoralis were studied. The results showed that root dry weight and the yield of G. littoralis increased when reasonably applied phosphorus fertilizer combined with potassium fertilizer within a certain range. And the influence of phosphorus fertilizer was greater than that of potassium fertilizer. The optimal value of root dry weight and yield achieved at both P2O5 360 kg x hm(-2), K2O 270 kg x hm(-2) and P2O5 360 kg x hm(-2), K2O 180 kg x hm(-2). The effects of different phosphorus and potassium treatments on the content of imperatorin, isoimperatorin and psoralen in G. littoralis were determined, which shows that the content increased with the moderate increase of phosphorus and potassium. And the effects of phosphorus fertilizer were more significantly. The isoimperatorin content achieved the largest value at P2O5 360 kg x hm(-2), K2O 270 kg x hm(-2), also a larger content of imperatorin and psoralen. The imperatorin content is the largest when applied P2O5 360 kg x hm(-2), K2O 180 kg x hm(-2), and the isoimperatorin content was higher as well. So that the treatment of P2O5 360 kg x hm(-2), K2O 180 kg x hm(-2) are suitable for promote to the agricultural production, which could improve the quality and yield of G. littoralis.