Optical vortex switch based on multiplexed volume gratings with high diffraction efficiency.

Systems of controllable orbital angular momentum (OAM) require more compact, higher conversion efficiency and more tolerable wavelength or polarization. We introduce an optical vortex switch based on a multiplexed volume grating (MVG). The MVG recorded in a piece of photo-thermo-refractive (PTR) glass exhibits high diffraction efficiency (DE, also known as conversion efficiency in transporting), sensitive angular selectivity, and polarization-insensitivity. The effects of the incident divergence angle and polarization on the DE and the far-field diffraction profiles are demonstrated and investigated. It turns out that the divergence angle of the probe beam can greatly affect the DE. The fluctuation of the DE caused by polarization variation is less than 1.59%. This switch can be potentially applied in vortex tweezers, optical communication, and high power systems.

Metabolic benefits of inhibition of p38α in white adipose tissue in obesity.

p38 has long been known as a central mediator of protein kinase A (PKA) signaling in brown adipocytes, which positively regulate the transcription of uncoupling protein 1 (UCP-1). However, the physiological role of p38 in adipose tissues, especially the white adipose tissue (WAT), is largely unknown. Here, we show that mice lacking p38α in adipose tissues display a lean phenotype, improved metabolism, and resistance to diet-induced obesity. Surprisingly, ablation of p38α causes minimal effects on brown adipose tissue (BAT) in adult mice, as evident from undetectable changes in UCP-1 expression, mitochondrial function, body temperature (BT), and energy expenditure. In contrast, genetic ablation of p38α in adipose tissues not only markedly facilitates the browning in WAT upon cold stress but also prevents diet-induced obesity. Consistently, pharmaceutical inhibition of p38α remarkably enhances the browning of WAT and has metabolic benefits. Furthermore, our data suggest that p38α deficiency promotes white-to-beige adipocyte reprogramming in a cell-autonomous manner. Mechanistically, inhibition of p38α stimulates the UCP-1 transcription through PKA and its downstream cAMP-response element binding protein (CREB), which form a positive feedback loop that functions to reinforce the white-to-beige phenotypic switch during cold exposure. Together, our study reveals that inhibition of p38α is able to promote WAT browning and confer metabolic benefits. Our study also indicates that p38α in WAT represents an exciting pharmacological target to combat obesity and metabolic diseases.

Accurate temperature measurement of a spectral beam combination grating based on VO2 film.

In a spectral beam combination system, temperature increase of the multilayer dielectric grating (MDG) worsens the far-field beam quality of the output laser. To accurately monitor the surface temperature of the MDG, this study deposits VO2 phase-change film on the lowest layer of multilayer dielectric films in the MDG and tests the transmittance with a probe laser. Based on this measurement, the surface temperature of the MDG can be calculated. Additionally, the study analyzes the influence of VO2 film on the surface electric field and the -1 diffraction efficiency of the MDG and presents a specific example of using VO2 film to test high reflector temperature. The study concludes that VO2 film is a feasible method of measuring temperature and better than an infrared thermal imager.

Continuous-wave laser damage mechanism of a spectral combining grating.

With increased power of spectral beam combination, surface heat distortion of multilayer dielectric gratings (MDGs) could occur. In this study, the damage morphology of MDGs was initially analyzed under a continuous-wave laser irradiation. Subsequently, the surface distortion and temperature rise of different MDGs were tested experimentally. The experimental results showed that the initial damage of MDGs was caused by the thermal stress. Further, the thermal stress of the multilayer dielectric films on the MDG surface was analyzed theoretically. The calculated results were in good agreement with the experimental results. The conclusions indicated that with the increase of the MDG surface temperature, the stress in the HfO2 layers initially reached the stress damage threshold of the dielectric films and, therefore, the damage occurred.

[Molecular Mechanism of Ventilator-associated Lung Injury Based on Keap1/Nfr2/ARE Signaling Pathway].

OBJECTIVE: To explore the molecular mechanism of ventilation induced lung injury (VILI) formation based on Keap1/Nfr2/ARE signaling pathway. METHODS: The VILI model was established by excessive mechanical ventilation in SD rats. HE staining was used to detect the pathological changes of lung tissue in the control group, normal tidal volume (VT) group and large VT group (VT 40 mL/kg). The wet weight of lung tissue was detected in each group. Dry weight (W/D) ratio change; BCA method was used to detect the changes of total protein in bronchoalveolar lavage fluid (BALF) of each group; ELISA was used to detect interleukin-1ß (IL-1ß) and leukocyte in BALF and serum of each group. The content of 8-OHdG in the lung tissue was detected by IL-8 and the content of malondialdehyde (MDA) in the lung tissue was detected by TBA method. The NLRP3, ASC and caspase-1 proteins in macrophages were detected by Western blot. The changes of Keap1 and Nrf2 proteins in lung tissues were detected by RT-PCR. The expressions of SOD mRNA and HO-1 mRNA in lung tissues of each group were detected by RT-PCR. RESULTS: Excessive mechanical ventilation could damage lung tissue, leading to alveolar rupture, inflammatory cell infiltration and erythrocytosis. Compared with the control group and normal VT group, the W/D value, 8-OHdG and MDA content in the large VT group, and total BALF, the contents of IL-1ß and IL-18 in protein, IL-1ß, IL-18 in serum increased significantly ( P<0.05). Compared with the control group and normal VT group, NLRP3, ASC, in macrophage of large VT group, the content of Keap1 protein in caspase-1 protein and lung tissue increased significantly ( P<0.05). The expression of Nrf2 protein, SOD mRNA and HO-1 mRNA in lung tissue decreased significantly. CONCLUSIONS: Large VT ventilation can cause acute inflammatory injury in lung tissue and lead to the occurrence of VILI. Inflammatory bodies of NLRP3 in alveolar macrophages are involved in this process, and the mechanism of NLRP3 inflammatory bodies is caused by hyperventilation in addition to mechanical injury. Decreased Keap1/Nrf2-ARE pathway inhibition and ROS clearance may also cause macrophage production of NLRP3 inflammatory bodies.

Ligand-dependent corepressor (LCoR) represses the transcription factor C/EBPß during early adipocyte differentiation.

Nuclear receptors (NRs) regulate gene transcription by recruiting coregulators, involved in chromatin remodeling and assembly of the basal transcription machinery. The NR-associated protein ligand-dependent corepressor (LCoR) has previously been shown to suppress hepatic lipogenesis by decreasing the binding of steroid receptor coactivators to thyroid hormone receptor. However, the role of LCoR in adipogenesis has not been established. Here, we show that LCoR expression is reduced in the early stage of adipogenesis in vitro LCoR overexpression inhibited 3T3-L1 adipocyte differentiation, whereas LCoR knockdown promoted it. Using an unbiased affinity purification approach, we identified CCAAT/enhancer-binding protein ß (C/EBPß), a key transcriptional regulator in early adipogenesis, and corepressor C-terminal binding proteins as potential components of an LCoR-containing complex in 3T3-L1 adipocytes. We found that LCoR directly interacts with C/EBPß through its C-terminal helix-turn-helix domain, required for LCoR's inhibitory effects on adipogenesis. LCoR overexpression also inhibited C/EBPß transcriptional activity, leading to inhibition of mitotic clonal expansion and transcriptional repression of C/EBPα and peroxisome proliferator-activated receptor γ2 (PPARγ2). However, LCoR overexpression did not affect the recruitment of C/EBPß to the promoters of C/EBPα and PPARγ2 in 3T3-L1 adipocytes. Of note, restoration of PPARγ2 or C/EBPα expression attenuated the inhibitory effect of LCoR on adipogenesis. Mechanistically, LCoR suppressed C/EBPß-mediated transcription by recruiting C-terminal binding proteins to the C/EBPα and PPARγ2 promoters and by modulating histone modifications. Taken together, our results indicate that LCoR negatively regulates early adipogenesis by repressing C/EBPß transcriptional activity and add LCoR to the growing list of transcriptional corepressors of adipogenesis.

High-efficiency polarization-independent wideband multilayer dielectric reflective bullet-alike cross-section fused-silica beam combining grating.

A high-efficiency polarization-independent wideband multilayer dielectric reflective bullet-alike cross-section (combination of trapezoidal-rectangular grating profile) fused-silica beam combining grating (BCG) used in the -1st order for spectral beam combining (SBC) is designed and fabricated. Exact grating profile parameters are optimized by using the rigorous coupled-wave analysis and simulated annealing algorithm. As a comparison, traditional pure trapezoidal and pure rectangular gratings are also designed. Numerical results show that such a bullet-alike cross-section BCG exhibits wide bandwidth with the lowest maximum electric field enhancement in the grating material, which is greatly beneficial for the promotion of the power scaling level of the grating-based SBC system. A two-step dry-etching procedure is developed to fabricate such a grating. The averaged diffraction efficiency of greater than 91% was experimentally demonstrated.

CaMKK2 Suppresses Muscle Regeneration through the Inhibition of Myoblast Proliferation and Differentiation.

Skeletal muscle has a major role in locomotion and muscle disorders are associated with poor regenerative efficiency. Therefore, a deeper understanding of muscle regeneration is needed to provide a new insight for new therapies. CaMKK2 plays a role in the calcium/calmodulin-dependent kinase cascade; however, its role in skeletal muscle remains unknown. Here, we found that CaMKK2 expression levels were altered under physiological and pathological conditions including postnatal myogensis, freeze or cardiotoxin-induced muscle regeneration, and Duchenne muscular dystrophy. Overexpression of CaMKK2 suppressed C2C12 myoblast proliferation and differentiation, while inhibition of CaMKK2 had opposite effect. We also found that CaMKK2 is able to activate AMPK in C2C12 myocytes. Inhibition of AMPK could attenuate the effect of CaMKK2 overexpression, while AMPK agonist could abrogate the effect of CaMKK2 knockdown on C2C12 cell differentiation and proliferation. These results suggest that CaMKK2 functions as an AMPK kinase in muscle cells and AMPK mediates the effect of CaMKK2 on myoblast proliferation and differentiation. Our data also indicate that CaMKK2 might inhibit myoblast proliferation through AMPK-mediated cell cycle arrest by inducing cdc2-Tyr15 phosphorylation and repress differentiation through affecting PGC1α transcription. Lastly, we show that overexpressing CaMKK2 in the muscle of mice via electroporation impaired the muscle regeneration during freeze-induced injury, indicating that CaMKK2 could serve as a potential target to treat patients with muscle injury or myopathies. Together, our study reveals a new role for CaMKK2 as a negative regulator of myoblast differentiation and proliferation and sheds new light on the molecular regulation of muscle regeneration.

Hepatic p38α regulates gluconeogenesis by suppressing AMPK.

BACKGROUND & AIMS: It is proposed that p38 is involved in gluconeogenesis, however, the genetic evidence is lacking and precise mechanisms remain poorly understood. We sought to delineate the role of hepatic p38α in gluconeogenesis during fasting by applying a loss-of-function genetic approach. METHODS: We examined fasting glucose levels, performed pyruvate tolerance test, imaged G6Pase promoter activity, as well as determined the expression of gluconeogenic genes in mice with a targeted deletion of p38α in liver. Results were confirmed both in vivo and in vitro by using an adenoviral dominant-negative form of p38α (p38α-AF) and the constitutively active mitogen-activated protein kinase 6, respectively. Adenoviral dominant-negative form of AMP-activated protein kinase α (DN-AMPKα) was employed to test our proposed model. RESULTS: Mice lacking hepatic p38α exhibited reduced fasting glucose level and impaired gluconeogenesis. Interestingly, hepatic deficiency of p38α did not result in an alteration in CREB phosphorylation, but led to an increase in AMPKα phosphorylation. Adenoviral DN-AMPKα could abolish the effect of p38α-AF on gluconeogenesis. Knockdown of up-steam transforming growth factor ß-activated kinase 1 decreased the AMPKα phosphorylation induced by p38α-AF, suggesting a negative feedback loop. Consistently, inverse correlations between p38 and AMPKα phosphorylation were observed during fasting and in diabetic mouse models. Importantly, adenoviral p38α-AF treatment ameliorated hyperglycemia in diabetic mice. CONCLUSIONS: Our study provides evidence that hepatic p38α functions as a negative regulator of AMPK signaling in maintaining gluconeogenesis, dysregulation of this regulatory network contributes to unrestrained gluconeogenesis in diabetes, and hepatic p38α could be a drug target for hyperglycemia.

Unified beam splitter of fused silica grating under the second Bragg incidence.

A unified design for a 1×2 beam splitter of dielectric rectangular transmission gratings under the second Bragg incidence is theoretically investigated for TE- and TM-polarized light. The empirical equations of the relative grating parameters (ratio of the absolute one to incidence wavelength) for this design are also obtained with the simplified modal method (SMM). The influences of polarization of incident light and relative grating parameters on the performance of the beam splitter are thoroughly studied based on the SMM and rigorous coupled-wave analysis. Two specific gratings are demonstrated with an even split and high diffraction efficiency (>94% for TE polarization and >97% for the TM counterpart). The unified profiles of the 1×2 beam splitter are independent from the incidence wavelength since the refractive index of fused silica is roughly a constant over a wide range of wavelengths, which should be promising for future applications.

Simple design of slanted grating with simplified modal method.

A simplified modal method (SMM) is presented that offers a clear physical image for subwavelength slanted grating. The diffraction characteristic of the slanted grating under Littrow configuration is revealed by the SMM as an equivalent rectangular grating, which is in good agreement with rigorous coupled-wave analysis. Based on the equivalence, we obtained an effective analytic solution for simplifying the design and optimization of a slanted grating. It offers a new approach for design of the slanted grating, e.g., a 1×2 beam splitter can be easily designed. This method should be helpful for designing various new slanted grating devices.

Mode conversion and coupling in a slanted grating.

We have proposed a novel transmission slanted grating at the central wavelength of 1550 nm, which can be used in optical communication. We have presented an approximate analytical expression that provides an insightful physical description of the simplified modal method for the slanted grating. The odd grating mode, which only exists in the asymmetric structure under normal incidence, plays the positive role of enhancing the -1st order diffraction efficiency. The analytic expressions of mode conversion and coupling can be obtained to explain the asymmetric field distribution, which cannot occur in the rectangular grating region. Numerical results achieved by the rigorous wave analysis verify the validity of the simplified modal method. We expect that the theoretical modal method set forth in this work will be helpful for the tremendous potential application of the slanted grating.

Multiple-channel guided mode resonance Brewster filter with controllable spectral separation.

In this work, a single-layer, multiple-channel guided mode resonance (GMR) Brewster filter with controllable spectral separation is proposed using the plane waveguide method and rigorous coupled-wave analysis. Based on the normalized eigenvalue equation, the controllability of the spectral separation is analyzed when the fill ratio of the grating layer is changed while its effective index is identical to that of the substrate. The location and the separation between resonances can be specifically controlled by modifying the fill ratio of the grating layer. In contrast to the ordinary GMR filter, where the location of the resonances is material dependent, it is demonstrated that the spectral separation for the first and second resonances can be linearly controlled by altering the fill ratio of the grating layer. In addition, the maximal shift of the second resonance is up to 5% of the first resonant wavelength using the single-layer Brewster filter.

High-efficiency fused-silica reflection grism.

A fused-silica reflection grism (combination of grating and prism) based on the phenomenon of total internal reflection (TIR), and used in the -1st order, is designed and fabricated. The grism is etched directly into the fused-silica prism, which greatly facilitates the use of the TIR grating as no other angle coupling devices are involved. The grating profile is optimized by the use of the rigorous coupled-wave analysis method. Diffraction efficiency of larger than 99% at a wavelength of 980 nm for TM-polarized waves can be theoretically obtained. Two-beam interference lithography and inductively coupled plasma etching techniques are used to manufacture such grism. Diffraction efficiencies of larger than 95% are experimentally demonstrated.

Head Horn Enhances Hydrodynamic Perception in Eyeless Cavefish.

Fish can use hydrodynamic stimuli, decoded by lateral line systems, to explore the surroundings. Eyeless species of the genus Sinocyclocheilus have evolved conspicuous horns on their heads, whereas the specific function of which is still unknown. Meanwhile, the eyeless cavefish exhibits more sophisticated lateral line systems and enhanced behavioral capabilities (for instance rheotaxis), compared with their eyed counterparts. Here, the influence of head horn on the hydrodynamic perception capability is investigated through computational fluid dynamics, particle image velocimetry, and a bioinspired cavefish model integrated with an artificial lateral line system. The results show strong evidence that the head horn structure can enhance the hydrodynamic perception, from aspects of multiple hydrodynamic sensory indicators. It is uncovered as that the head horn renders eyeless cavefish with stronger hydrodynamic stimuli, induced by double-stagnation points near the head, which are perceived by the strengthened lateral line systems. Furthermore, the eyeless cavefish model has ≈17% higher obstacle recognition accuracy and lower cost (time and sensor number) than eyed cavefish model is conceptually demonstrated, by incorporating with machine learning. This study provides novel insights into form-function relationships in eyeless cavefish, in addition paves the way for optimizing sensor arrangement in fish robots and underwater vehicles.

Histone-methyltransferase KMT2D deficiency impairs the Fanconi anemia/BRCA pathway upon glycolytic inhibition in squamous cell carcinoma.

Histone lysine methyltransferase 2D (KMT2D) is the most frequently mutated epigenetic modifier in head and neck squamous cell carcinoma (HNSCC). However, the role of KMT2D in HNSCC tumorigenesis and whether its mutations confer any therapeutic vulnerabilities remain unknown. Here we show that KMT2D deficiency promotes HNSCC growth through increasing glycolysis. Additionally, KMT2D loss decreases the expression of Fanconi Anemia (FA)/BRCA pathway genes under glycolytic inhibition. Mechanistically, glycolytic inhibition facilitates the occupancy of KMT2D to the promoter/enhancer regions of FA genes. KMT2D loss reprograms the epigenomic landscapes of FA genes by transiting their promoter/enhancer states from active to inactive under glycolytic inhibition. Therefore, combining the glycolysis inhibitor 2-DG with DNA crosslinking agents or poly (ADP-ribose) polymerase (PARP) inhibitors preferentially inhibits tumor growth of KMT2D-deficient mouse HNSCC and patient-derived xenografts (PDXs) harboring KMT2D-inactivating mutations. These findings provide an epigenomic basis for developing targeted therapies for HNSCC patients with KMT2D-inactivating mutations.

Multireflection modal method for wideband fused-silica transmission gratings.

A multireflection modal method is proposed to give a clear physical picture for explanation of the diffraction process that takes place in a wideband fused-silica transmission grating. Using rigorous coupled-wave analysis, the optimized grating exhibits diffraction efficiency greater than 93.9% for TE polarization over a bandwidth of 126 nm (from 735 to 861 nm). The designed wideband fused-silica transmission grating is fabricated using holographic interference recording and inductively coupled plasma etching technology. Experimental results are in agreement with the theoretical values.

400nm ultra-broadband gratings for near-single-cycle 100 Petawatt lasers.

Compressing high-energy laser pulses to a single-cycle and realizing the "λ3 laser concept", where λ is the wavelength of the laser, will break the current limitation of super-scale projects and contribute to the future 100-petawatt and even Exawatt lasers. Here, we have realized ultra-broadband gold gratings, core optics in the chirped pulse amplification, in the 750-1150 nm spectral range with a > 90% -1 order diffraction efficiency for near single-cycle pulse stretching and compression. The grating is also compatible with azimuthal angles from -15° to 15°, making it possible to design a three-dimensional compressor. In developing and manufacturing processes, a crucial grating profile with large base width and sharp ridge is carefully optimized and controlled to dramatically broaden the high diffraction efficiency bandwidth from the current 100-200 nm to over 400 nm. This work has removed a key obstacle to achieving the near single-cycle 100-PW lasers in the future.

Three-dimensional Dammann array.

We demonstrate a scheme that can produce a three-dimensional (3D) focus spot array in a 3D lattice structure, called a 3D Dammann array, in focal region of an objective. This 3D Dammann array is generated by using two separate micro-optical elements, a Dammann zone plate (DZP) that produces a series of coaxial focus spots and a conventional two-dimensional (2D) Dammann grating (DG). A simple, fast, and clear method is presented to design this binary pure-phase (0,π) DZP in vectorial Debye theory regime. Based on this kind of DZP, one can always obtain a 3D Dammann array both for low and high numerical aperture (NA) focusing objectives. For experimental demonstration, an arrangement combining a DZP, a 2D DG, and a pair of opposing lenses is proposed to generate a 5×5×5 Dammann array in focal region of an objective with NA=0.127 and another 6×6×7 Dammann array for an objective of NA=0.66. It is shown that this arrangement makes it possible to achieve 3D Dammann arrays with micrometer-sized focus spots and focus spacings of tens of micrometers for various practical applications, such as 3D parallel micro- and nanomachining, 3D simultaneous optical manipulation, 3D optical data storage, and multifocal fluorescence microscope, etc.

Polarization-independent wideband mixed metal dielectric reflective gratings.

A polarization-independent wideband mixed metal dielectric grating with high efficiency of the -1st order is analyzed and designed in Littrow mounting. The mixed metal dielectric grating consists of a rectangular-groove transmission dielectric grating on the top layer and a highly reflective mirror composed of a connecting layer and a metal film. Simplified modal analysis is carried out, and it shows that when the phase difference accumulated by the two propagating modes is odd multiples of π/2, the diffraction efficiency of the -1st order will be high. Selecting grating depth and duty cycle for satisfying the phase difference condition for both TE (electric field parallel to grooves) and TM (magnetic field parallel to grooves) polarizations, a polarization-independent high-efficiency grating can be designed. Using rigorous coupled-wave analysis and a simulated annealing algorithm, geometric parameters of the reflective grating are exactly obtained. The optimized grating for operation around a wavelength of 800 nm exhibits diffraction efficiencies higher than 90% for both TE and TM polarizations over a 120 nm wavelength bandwidth. The simplified modal analysis can be applied in other types of reflective gratings if the top layer is a dielectric transmission grating.