Search

Metabotropic glutamate receptor 2 (GRM2) is highly expressed in hippocampal dentate granule cells (DGCs), regulating synaptic transmission and hippocampal functions. Newborn DGCs are continuously generated throughout life and express GRM2 when they are mature. However, it remained unclear whether and how GRM2 regulates the development and integration of these newborn neurons. We discovered that the expression of GRM2 in adult-born DGCs increased with neuronal development in mice of both sexes. Lack of GRM2 caused developmental defects of DGCs and impaired hippocampus-dependent cognitive functions. Intriguingly, our data showed that knockdown ofGrm2resulted in decreased b/c-Raf kinases and paradoxically led to an excessive activation of MEK/ERK1/2 pathway. Inhibition of MEK ameliorated the developmental defects caused byGrm2knockdown. Together, our results indicate that GRM2 is necessary for the development and functional integration of newborn DGCs in the adult hippocampus through regulating the phosphorylation and activation state of MEK/ERK1/2 pathway.SIGNIFICANCE STATEMENTMetabotropic glutamate receptor 2 (GRM2) is highly expressed in mature dentate granule cells (DGCs) in the hippocampus. It remains unclear whether GRM2 is required for the development and integration of adult-born DGCs. We providedin vivoandin vitroevidence to show that GRM2 regulates the development of adult-born DGCs and their integration into existing hippocampal circuits. Lack of GRM2 in a cohort of newborn DGCs impaired object-to-location memory in mice. Moreover, we revealed that GRM2 knockdown paradoxically upregulated MEK/ERK1/2 pathway by suppressing b/c-Raf in developing neurons, which is likely a common mechanism underlying the regulation of the development of neurons expressing GRM2. Thus, Raf/MEK/ERK1/2 pathway could be a potential target for brain diseases related to GRM2 abnormality.

In order to solve the difficulty of traditional phase measuring deflectometry (PMD) in considering precision and speed, an orthogonal encoding PMD method based on deep learning is presented in this paper. We demonstrate for, what we believe to be, the first time that deep learning techniques can be combined with dynamic-PMD and can be used to reconstruct high-precision 3D shapes of specular surfaces from single-frame distorted orthogonal fringe patterns, enabling high-quality dynamic measurement of specular objects. The experimental results prove that the phase and shape information measured by the proposed method has high accuracy, almost reaching the results obtained by the ten-step phase-shifting method. And the proposed method also has excellent performance in dynamic experiments, which is of great significance to the development of optical measurement and fabrication areas.

We first report a single-light-source orthogonally pumped triaxial atomic magnetometer with a double-cell structure. By using a beam splitter to equally allocate the pump beam, the proposed triaxial atomic magnetometer is responsive to magnetic fields in all three directions, and without sacrificing system sensitivity. The experimental results indicate that, the magnetometer achieves a sensitivity of 22 fT/Hz1/2 in x-direction with a 3-dB bandwidth of 22 Hz, a sensitivity of 23 fT/Hz1/2 in y-direction with a 3-dB bandwidth of 23 Hz, and a sensitivity of 21 fT/Hz1/2 in z-direction with a 3-dB bandwidth of 25 Hz. This magnetometer is useful for the applications that require the measurements of the three components of the magnetic field.

Hippocampal neurogenesis declines with aging. Wnt ligands and antagonists within the hippocampal neurogenic niche regulate the proliferation of neural progenitor cells and the development of new neurons, and the changes of their levels in the niche mediate aging-associated decline of neurogenesis. We found that RNA-binding protein Lin28a remained existent in neural progenitor cells and granule neurons in the adult hippocampus, and decreased with aging. Loss of Lin28a inhibited the responsiveness of neural progenitor cells to niche Wnt agonist and reduced neurogenesis, thus impairing pattern separation. Overexpression of Lin28a increased the proliferation of neural progenitor cells, promoted the functional integration of newborn neurons, restored neurogenesis in Wnt-deficient dentate gyrus, and rescued the impaired pattern separation in aging mice. Our data suggest that Lin28a regulates adult hippocampal neurogenesis as an intracellular mechanism by responding to niche Wnt signals, and its decrease is involved in aging-associated decline of hippocampal neurogenesis as well as related cognitive functions.

Background Lignin is a complex aromatic heteropolymer comprising 15–30% dry weight of the lignocellulose. The complex structural characteristic of lignin renders it difficult for value-added utilization. Exploring efficient lignin-degrading microorganisms and investigating their lignin-degradation mechanisms would be beneficial for promoting lignin valorization. In this study, a newly isolated white-rot basidiomycete, Trametes hirsuta X-13, with capacity to utilize alkaline lignin as the sole substrate was investigated. Results The analysis of the fermentation properties of T. hirsuta X-13 using alkaline lignin as the sole substrate, including the mycelial growth, activities of ligninolytic enzymes and the rates of lignin degradation and decolorization confirmed its great ligninolysis capacity. The maximum lignin degradation rate reached 39.8% after 11 days of T. hirsuta X-13 treatment, which was higher than that of reported fungi under the same condition. Fourier transform infrared spectrometry (FTIR), gas chromatography–mass spectrometry (GC–MS) scanning electron micrographs (SEM), two-dimensional heteronuclear single quantum coherence NMR analysis (2D-HSQC NMR) collaborated with pyrolysis gas chromatography–mass spectrometry (py-GC/MS) analyses proved that lignin structure was severely deconstructed along with amounts of monomer aromatics generated. Furthermore, according to those chemical analysis, in addition to canonical Cα–Cβ breakage, the cleavage of lignin interunit linkages of β–β might also occur by T. hirsuta X-13. Conclusions This study characterized a newly isolated white-rot basidiomycete T. hirsuta X-13 with impressive alkaline lignin degradation ability and provided mechanistic insight into its ligninolysis mechanism, which will be valuable for the development of lignin valorization strategies.

Background Pretreatment is a critical step required for efficient conversion of woody biomass into biofuels and platform chemicals. Fungal pretreatment is regarded as one of the most promising technology for woody biomass conversion but remains challenging for industrial application. The exploration of potential fungus strain with high efficient delignification and less processing time for woody biomass pretreatment will be valuable for development of biorefinery industry. Here, a newly isolated white-rot basidiomycete Peniophora incarnate T-7 was employed for poplar wood pretreatment. Results The chemical component analysis showed that cellulose, hemicellulose and lignin from poplar wood declined by 16%, 48% and 70%, respectively, after 7 days submerged fermentation by P. incarnate T-7. Enzymatic saccharification analysis revealed that the maximum yields of glucose and xylose from 7 days of P. incarnate T-7 treated poplar wood reached 33.4% and 27.6%, respectively, both of which were enhanced by sevenfold relative to the untreated group. Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), X-ray diffraction (XRD) and pyrolysis gas chromatography–mass spectrometry (Py-GC/MS) characterization confirmed that lignocellulosic structure of poplar wood was largely broken by P. incarnate T-7, including delignification and de-crystalline of cellulose. Meanwhile, lignin component of poplar wood was selectively degraded by P. incarnate T-7, and G-type unit of lignin was preferentially attacked by the strain. Furthermore, quantitative proteomic analysis revealed that a considerable amount of lignocellulolytic enzymes were detected in the secretory proteins of P. incarnate T-7, especially with high abundance of lignin-degrading enzymes and hemicellulases. Combination of quantitative proteomic with transcriptomic analysis results showed that most of those lignocellulolytic enzymes were highly upregulated on poplar wood substrate compared to glucose substrate. Conclusions This study showed that P. incarnate T-7 could selectively delignify poplar wood by submerged fermentation with short time of 7 days, which greatly improved its enzymatic saccharification efficiency. Our results suggested that P. incarnate T-7 might be a promising candidate for industrial woody biomass pretreatment.

In this paper, we investigate the output performance of a continuous-wave Ho3+-doped fluoride fiber laser operating at 3.92 µm from the 5I5 → 5I6 transition of Ho3+ using numerical simulation. A double-clad Ho3+-doped fluoroindate fiber with a doping concentration of 10.0 mol.% is assumed, with direct pumping at 888 nm. We propose simultaneous lasing on the 5I6 → 5I7 transition to enhance the slope efficiency while reducing the threshold and heat accumulation. Simulation results indicate that a slope efficiency of 17% and a threshold of 2.5 W can be obtained using a 9 cm-long fiber. Moreover, with the heat accumulation reduced by >40%, watt level laser output can be achieved in this cascade system at room temperature without the gain fiber being damaged by heat accumulation. The theoretical maximum output power of 1.27 W is 6 times higher than the highest reported value (197 mW), which is limited by the fiber damage due to excess heat load.

Phase Measuring Deflectometry (PMD) and Structured-Light Modulation Analysis Technique (SMAT) perform effectively in shape and defect measurements of specular objects, but the difficulty of giving consideration to accuracy and speed has also restricted the further development and application of them. Inspired by recent successes of deep learning techniques for computational imaging, we demonstrate for the first time that deep learning techniques can be used to recover high-precision modulation distributions of specular surfaces from a single-frame fringe pattern under SMAT, enabling fast and high-quality defect detection of specular surfaces. This method can also be applied to recover higher-precision phase distributions of specular surfaces from a single-frame fringe pattern under PMD, so as to realize the 3D shape measurement. In this paper, we combine depthwise separable convolution, residual structure and U-Net to build an improved U-Net network. The experimental results prove that the method has excellent performance in the phase and modulation retrieval of specular surfaces, which almost reach the accuracy of the results obtained by ten-step phase-shifting method.

The existing analytical gradient models in phase measuring deflectometry (PMD) usually suffer in the ambiguous problem. To solve this problem, simplification/assumption is often given to the surface shape, which causes non-ignorable measurement error in certain situations. In order to analyze the relation between the surface shape and measurement error when simplification/assumption is used, a ray tracing simulation model is developed in this paper. For any given PMD system setup, the relation between the height/slope variations of test surface and measurement accuracy can be carried out. The corresponding experiment work proves the correctness of this simulation model. The increasing of either the height or slope of object will lead to the exponential aggravating of measurement error. For our experiment setup, the measurement gradient error will be less than 0.5% if the ratio of the distance between the LCD (Liquid Crystal Display) screen and the reference plane and the STD (standard derivation) of object height is larger than 200. Keywords: Phase measuring deflectometry, Optical 3D measurement, Error analysis, Ray tracing model

Under natural conditions, injured cells can be repaired rapidly through inherent biological processes. However, in the case of diabetes, cardiovascular disease, muscular dystrophy, and other degenerative conditions, the natural repair process is impaired. Repair of injury to the cell membrane is an important aspect of physiology. Inadequate membrane repair function is implicated in the pathophysiology of many human disorders. Recent studies show that Mitsugumin 53 (MG53), a TRIM family protein, plays a key role in repairing cell membrane damage and facilitating tissue regeneration. Clarifying the role of MG53 and its molecular mechanism are important for the application of MG53 in regenerative medicine. In this review, we analyze current research dissecting MG53′s function in cell membrane repair and tissue regeneration, and highlight the development of recombinant human MG53 protein as a potential therapeutic agent to repair multiple-organ injuries.

Background In the past 30 years, incidences of non-alcoholic fatty liver disease (NAFLD) has risen by 30%. However, there is still no clear mechanism or accurate method of anticipating liver failure. Here we reveal the phase transitions of liquid crystalline qualities in hepatic lipid droplets (HLDs) as a novel method of anticipating prognosis. Methods NAFLD was induced by feeding C57BL/6J mice on a high-fat (HiF) diet. These NAFLD livers were then evaluated under polarized microscopy, X-ray diffraction and small-angle scattering, lipid component chromatography analysis and protein expression analysis. Optically active HLDs from mouse model and patient samples were both then confirmed to have liquid crystal characteristics. Liver MAP1LC3A expression was then evaluated to determine the role of autophagy in liquid crystal HLD (LC-HLD) formation. Results Unlike the normal diet cohort, HiF diet mice developed NAFLD livers containing HLDs exhibiting Maltese cross birefringence, phase transition, and fluidity signature to liquid crystals. These LC-HLDs transitioned to anisotropic crystal at 0 °C and remain crystalline. Temperature increase to 42 °C causes both liquid crystal and crystal HLDs to convert to isotropic droplet form. These isotropic HLDs successfully transition to anisotropic LC with fast temperature decrease and anisotropic crystal with slow temperature decrease. These findings were duplicated in patient liver. Patient LC-HLDs with no inner optical activity were discovered, hinting at lipid saturation as the mechanism through which HLD acquire LC characteristics. Downregulation of MAP1LC3A in conjunction with increased LC-HLD also implicated autophagy in NAFLD LC-HLD formation. Conclusions Increasing concentrations of amphiphilic lipids in HLDs favors organization into alternating hydrophilic and hydrophobic layers, which present as LC-HLDs. Thus, evaluating the extent of liquid crystallization with phase transition in HLDs of NAFLD patients may reveal disease severity and predict impending liver damage.

With the rapid development of electronic industry, higher and higher requirements are placed on the surface quality of optical components in electronic devices. Structured-Light Modulation Analysis Technique (SMAT) was recently proposed to detect the contamination and defects on specular surfaces. In this paper, the proposed mechanisms and mathematical models of SMAT are analyzed and established based on the theory of photometry and the optical characteristics of contamination and defects for the first time. What's more, a novel transmission system adopting SMAT is especially designed for the defect detection of transparent objects. For both reflection and transmission system, simulations and experiments were conducted, and comparative studies with uniform planar illumination were also carried out. Simulations on the influence of incident light source region showed that SMAT can eliminate the interference of ambient light while uniform planar illumination technique cannot. Experiments on samples with specular surface and transparent material demonstrated that the modulation values at the contamination and defects are much less than that at clean and intact place, and defects and contaminations were clearly distinguished based on SMAT, while they were almost indiscernible with uniform planar illumination. Therefore, SMAT can be applied to the whole-field inspection of optical components in industrial environments.

B lymphocyte and macrophages may contribute to SLE pathogenesis through cytokine production after TLR stimulation. Emerging evidences suggested that defects of sphingolipid metabolism were responsible for SLE pathogenesis. However, it is not clear whether these defects exist in B cells and macrophages under SLE condition and whether TLR signalling pathway was related to the dysfunction of sphingolipid metabolism in SLE. Here, we demonstrated that the enzymes involved in the sphingolipid metabolism expressed abnormally in B cells from SLE patients and lupus-prone mice. Moreover, we found that TLR signalling induced the abnormal expression of sphingomyelin phosphodiesterase 3 (SMPD3), sphingosine-1-phosphate phosphatase 2 (SGPP2), ceramide kinase (CERK) and UDP glycosyltransferase 8 (UGT8), which were involved in sphingolipid metabolism. TLR signalling also induced the transportation of SMPD3 from Golgi apparatus. Furthermore, the dysfunction of SMPD3 enhanced TLR-induced inflammatory response of B cells and macrophages in turn. Thus, these findings provide an innovative direction and a new target for research and treatment of SLE.

Context: The natural polyphenolic compound curcumin has been proved to modulate innate immune responses and possess anti-inflammatory properties. Nevertheless, the mechanism remains poorly understood, particularly regarding curcumin-regulated miRNAs under inflammatory response. Objective: This study investigates the role of miRNA-155 in the effects of curcumin on inflammatory response in cell and a mouse model. Materials and methods: The anti-inflammatory activity of curcumin (5, 10 and 15 μM, 2 h) in lipopolysaccharide (LPS, 200 ng/mL)-induced cells were measured by quantitative PCR. The animals were treated orally by 20 mg/kg curcumin for 3 days before an LPS intraperitoneal injection (10 mg/kg, 16 h). MicroRNA (miRNA) expression and the underlying molecular mechanisms were assessed using transfection technique and western blotting. Results and discussion: Curcumin efficiently inhibited LPS-induced cytokines (TNF-α, IL-6) and microRNA-155 (miR-155) expression (p

Hirsutella sinensis, cultured in vitro, is an attractive substitute for Cordyceps sinensis as health supplement. The aim of this study was to demonstrate whether H. sinensis mycelium (HSM) attenuates murine pulmonary fibrosis induced by bleomycin and to explore the underlying molecular mechanisms. Using lung fibrosis modle induced by intratracheal instillation of bleomycin (BLM; 4 mg/kg), we observed that the administration of HSM reduced HYP, TGF-β1 and the production of several pro-fibrosis cytokines (α-smooth muscle actin, fibronectin and vimentin) in fibrotic mice lung sections. Histopathological examination of lung tissues also demonstrated that HSM improved BLM-induced pathological damage. Concurrently, HSM supplementation markedly reduced the chemotaxis of alveolar macrophages and potently suppressed the expression of inflammatory cytokines. Also, HSM influenced Th1/Th2 and Th17/Treg imbalance and blocked the phosphorylation of mTOR pathway in vivo. Alveolar epithelial A549 cells acquired a mesenchymal phenotype and an increased expression of myofibroblast markers of differentiation (vimentin and fibronectin) after treatment with TGF-β1. HSM suppressed these markers and blocked the phosphorylation of mTOR pathway in vitro. The results provide evidence supporting the use of HSM in the intervention of pulmonary fibrosis and suggest that HSM is a potential therapeutic agent for lung fibrosis.

The disorder of B cells is one of the hallmarks of systemic lupus erythematosus (SLE). The activation state indicated by CD86 of B cells from SLE is well known, while the defect of regulatory B cells mediated by CD1d is also responsible for the process of SLE. In the present study, we focused on the relationship between B cell activation mediated by CD86 and B cell regulatory function mediated by CD1d. Our results showed that the level of CD1d in B cells was decreased during the early stages of B6.MRLlpr SLE mice and imiquimod-treated (IMQ-treated) mice, while the level of CD86 was significantly increased at the late stage. Moreover, the expression of CD1d showed a significantly negative correlation with CD86 level in B cells from IMQ-treated mice (r = -05741; P = 0.0022), B6.MRLlpr mice (r = -0.7091; P = 0.0268), and SLE patients (r = -0.4125; P = 0.0404). The in vivo and in vitro experiments with splenocytes demonstrated that CD1d signaling pathway could inhibit toll-like receptor 7 (TLR7)-induced CD86 expression of B cells. Further studies showed that this relationship also affected antibody production. Thus, our results confirmed the association of CD1d and CD86 levels in B cells from SLE, and demonstrated the importance to preserve the immunoregulatory function of B cells mediated by CD1d in the progression of SLE.

The ability to accurately estimate the location and geometry of holes is often required in the field of quality control and automated assembly. Projected fringe profilometry is a potentially attractive technique on account of being non-contacting, of lower cost, and orders of magnitude faster than the traditional coordinate measuring machine (CMM). However, we demonstrate in this paper that fringe projection is susceptible to significant (hundreds of µm) measurement artefacts in the neighbourhood of hole edges, which give rise to errors of a similar magnitude in the estimated hole geometry. A mechanism for the phenomenon is identified based on the finite size of the imaging system’s point spread function and the resulting bias produced near to sample discontinuities in geometry and reflectivity. A mathematical model is proposed, from which a post-processing compensation algorithm is developed to suppress such errors around the holes. The algorithm includes a robust and accurate sub-pixel edge detection method based on a Fourier descriptor of the hole contour. The proposed algorithm was found to reduce significantly the measurement artefacts near the hole edges. As a result, the errors in estimated hole radius were reduced by up to one order of magnitude, to a few tens of µm for hole radii in the range 2-15 mm, compared to those from the uncompensated measurements.

The nanocrystalline ceria thin films doped with yttria of different concentrations were prepared by using the sol-gel dip-coating method. The complex impedance of the films was measured at various temperatures. It is found that the complex impedance spectroscopies of our nanocrystalline ceria-based thin films show only a residual grain boundary arc, and that the total impedance is increased with an increasing Y3+ concentration and is decreased as the operating temperature is raised.

In phase measuring deflectometry (PMD), a camera observes a sinusoidal fringe pattern via the surface of a specular object under test. Any slope variations of the surface lead to distortions of the observed pattern. Without height-angle ambiguity, carrier removal process is adopted to evaluate the variation of surface slope from phase distribution when a quasi-plane is measured. However, in the usual measurement system, the carrier phase will be nonlinear due to the restrictions of system geometries. In this paper, based on the analytical carrier phase description in PMD, a carrier removal method is proposed to remove the nonlinear carrier phase. Both the theoretical analysis and the experiment results are presented. By comparison with reference-subtraction method and series-expansion method, this proposed method can achieve carrier removal process with only the measurement of one single object, as well as high accuracy and time-saving.

In phase measuring deflectometry (PMD), the fringe pattern deformed according to slope deviation of a specular surface is digitized employing a phase-shift technique. Without height-angle ambiguity, carrier-removal process is adopted to evaluate the variation of surface slope from phase distribution when a quasi-plane is measured. However, the difficulty lies in the fact that the nonlinearity is generally contained in the carrier frequency due to the restrictions of system geometries. This paper investigates nonlinear carrier components introduced by the generalized imaging process in PMD. Furthermore, the analytical expression of carrier components in PMD is presented for the first time. The presented analytical form of carrier components can be extended to analyze and describe various effects of system parameters on carrier distortion. Assuming a pinhole perspective model, carrier phase distribution of arbitrary geometric arrangement is modeled as a function of spatial variables by exploring ray tracing method. As shown by simulation and experimental results, the carrier distortion is greatly affected by non-telecentric camera operation. Experimental results on the basis of reference subtraction technique further demonstrate that restrictions on reflection system geometry can be eliminated when the carrier phase is removed elaborately.