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The mechanisms underlying the pathogenesis of steatosis and insulin resistance in nonalcoholic fatty liver disease remain elusive. Increased phosphorylation of hepatic p38 has long been noticed in fatty liver; however, whether the activation of hepatic p38 is a cause or consequence of liver steatosis is unclear. Here, we demonstrate that hepatic p38 activation by MKK6 overexpression in the liver of mice induces severe liver steatosis, reduces fat mass, and elevates circulating fatty acid levels in a hepatic p38a- and FGF21-dependent manner. Mechanistically, through increasing the FGF21 production from liver, hepatic p38 activation increases the influx of fatty acids from adipose tissue to liver, leading to hepatic ectopic lipid accumulation and insulin resistance. Although hepatic p38 activation exhibits favorable effects in peripheral tissues, it impairs the hepatic FGF21 action by facilitating the ubiquitination and degradation of FGF21 receptor cofactor b-Klotho. Consistently, we show that p38 phosphorylation and FGF21 expression are increased, b-Klotho protein levels are decreased in the fatty liver of either mice or patients. In conclusion, our study reveals previously undescribed effects of hepatic p38 activation on systemic metabolism and provides new insights into the roles of hepatic p38a, FGF21, and b-Klotho in the pathogenesis of nonalcoholic fatty liver disease.

The predation behavior of the pistol shrimp is extremely special, and the predation process will produce a huge popping sound, which has caused extensive research by scholars from all over the world. This article carried out a study on the rapid closing jet mechanism of pistol shrimp’s claws. A theoretical model, based on the hydrodynamic characteristics of seawater and the theory of fluid-structure coupling, was proposed for the interaction between the claws and seawater. A simulation model was established using the finite volume software Fluent, and the rapid closing jet mechanism of pistol shrimp’s claws was verified by using fluid dynamic grid. This article studied the influence of different fluid models on the simulation results. The effects of the claws’ closing angular velocity and angular acceleration on the interaction between the claws and seawater were analyzed, which provides a theoretical basis for the development of new underwater kinetic energy weapons.

We determined the clinical value of metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) for the diagnosis of patients with suspected encephalitis or meningitis infection. Clinical data were collected and retrospectively analyzed from patients with suspected cases of encephalitis or meningitis who presented at four hospitals in Ningbo from January 1st, 2019 to December 31st, 2020. Of a total of 66 suspected cases, 41 (62.12%) were diagnosed with central nervous system infections, which included 18 cases (27.27%) of viral infection, 13 cases (19.70%) of bacterial infection, 3 cases (4.55%) of Mycobacterium tuberculosis, 5 cases (7.58%) of fungal infection, and 2 cases (3.03%) of Rickettsia infection. From these cases, mNGS identified 25 (37.88%) true-positive cases, 8 (12.12%) false-positive cases, 20 (30.30%) true-negative cases, and 13 (19.70%) false-negative cases. The sensitivity of mNGS was 65.79% with a specificity of 71.43%. The positive rate was higher compared with traditional methods (37.88% vs. 24.39%). The results indicate that mNGS technology is a more sensitive method for detecting suspected infectious encephalitis or meningitis compared with traditional pathogen detection methods.

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.

The laser-induced damage (LID) response of multilayer dielectric gratings (MDGs) to transverse magnetic (TM) and transverse electric polarization was investigated based on polarized-independent MDGs. It was found that TM-polarized MDGs have the superiority of a high LID threshold, low sensitivity to laser excitation strength, low response to damaged structure, and reduced LID growth speed and dynamics. These results provide a strong motive to preferentially develop and mount TM-polarized MDGs in the next generation of high-intensity picosecond-petawatt laser systems.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a breathing disorder associated with cognitive impairment. However, the mechanisms leading to cognitive deficits in OSAHS remain uncertain. In this study, a mouse model of chronic intermittent hypoxia (CIH) exposures were applied for simulating the deoxygenation-reoxygenation events occurring in OSAHS. The conventional adenosine A1 receptor gene (A1R) knockout mice and the A1R agonist CCPA- or antagonist DPCPX-administrated mice were utilized to determine the precise function of A1R signaling in the process of OSAHS-relevant cognitive impairment. We demonstrated that CIH induced morphological changes and apoptosis in hippocampal neurons. Further, CIH blunted hippocampal long-term potentiation (LTP) and resulted in learning/memory impairment. Disruption of adenosine A1R exacerbated morphological, cellular, and functional damage induced by CIH. In contrast, activation of adenosine A1R signaling reduced morphological changes and apoptosis of hippocampal neurons, promoted LTP, and enhanced learning and memory. A1Rs may up-regulate protein kinase C (PKC) and its subtype PKC-ζ through the activation of Gα(i) improve spatial learning and memory disorder induced by CIH in mice. Taken together, A1R signaling plays a neuroprotective role in CIH-induced cognitive dysfunction and pathological changes in the hippocampus.

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

The gold-coated photoresist grating (GCPG) compressor is a core module of the high-repetition-rate superintense ultrafast lasers. Understanding how pulse trains with different repetition rates lead to laser-induced damage of GCPG is critical for future high-power laser applications. In this paper, we present the results of a multi-pulse laser-induced damage threshold (LIDT) investigation of GCPGs at different high repetition rates for the first time. The upper and lower endurance limits of S-on-1 beam-normal LIDT at 50–1000 Hz (800 nm, 35 fs) are ∼0.40 J/cm2 and 0.01 J/cm2, respectively, and the multi-pulse LIDT at 100 kHz is ∼0.02 J/cm2 corresponding to the peak intensity ∼64 GW/cm2 (1030 nm, 320 fs). The typical damage morphologies at 50–1000 Hz that the gold coating strips from the photoresist grating mask differ from those initiated from the expansion of the mask at 100 kHz. Focused ion beam scanning electron microscopy measurements show that the corners and small adhesion strength of interfaces are structural weaknesses. Moreover, theoretical modeling indicates that the differences mainly arise from pyrolysis and low heat-conduction of the mask. Overall, these results are highly practical and lay the foundation for the safe construction of high-repetition-rate ultra-high-power lasers based on the GCPG compressor.

This paper presents a sub-wavelength moth-eye-like antireflective structure on lithium triborate (LiB3O5, LBO) surface that can effectively promote the transmittance and maintain high laser-induced damage threshold (LIDT). Fabricated by holographic lithography and reactive ion-beam etching techniques, sub-wavelength periodic arrays can be obtained on the crystal surface. The surface morphology and transmittance were measured with atomic force microscope and spectrophotometer respectively. Single-sided transmittance of the LBO with moth-eye-like structure was confirmed to exceed 98% in the wavelength range of 1028–1300 nm, while is 98.73% at 1064 nm. For 1064 nm laser with the pulse width of 12 ns, the measured 1-on-1 LIDT is 42.57 J/cm2, which is about 2.28 times that of LBO compared with traditional antireflection (AR) coatings.

We present a type of generalized circular Dammann gratings (GCDGs) with controllable impulse ring profiles. Different from impulse rings generated by traditional circular Dammann gratings, the intensity profile of impulse rings can be tuned by redesigning the phase structure of GCDGs. Also, the physical picture behind this controllable impulse ring profile is given clearly. As examples, four one-order binary (0, $\pi $ ) GCDGs are designed and fabricated for generation of impulse rings with four different intensity profiles. In addition, GCDGs with continuous-phase profile are also demonstrated for generation of multiple concentric equal-intensity impulse rings with different intensity profiles. This type of impulse rings with tunable intensity profiles will enrich the function of CDGs, and it should be of high interest for its potential applications in various realms, such as structured pumping laser, novel optical manipulation, generation of dark perfect vortices, and optical testing and measurement.

Growing evidence suggests that hepatic macrophages play an important role in tissue repair after liver injury by coordinating the induction and resolution of inflammation, removing apoptotic cells, and promoting hepatocyte proliferation. Understanding the role of macrophages in the pathogenesis of liver injury will help pave the way to future therapeutics. Here, we investigated whether macrophage p38α plays a regulatory role in the tissue repair following d-galactosamine (GalN)/tumor necrosis factor-α (TNF-α)-induced acute liver injury. We found that macrophage p38α-deficient mice displayed decreased mortality and relieved liver injury as evident from less apoptosis, accelerated regeneration, decreased granulocytes recruitment, monocytes infiltration, and cytokine production after GalN/TNF-α treatment. Mechanistically, we found that p38 signaling was activated by lipopolysaccharide/interferon-γ treatment but not by inteleukin-4 stimulation, while pharmaceutical inhibition of p38α induced a shift in polarization from M1 macrophages to M2 macrophages. Together, our results indicated that macrophage p38α signaling is involved in the pathogenesis of liver injury induced by GalN/TNF-α, and inhibition of p38α signaling in macrophage could ameliorate liver injury and accelerate regeneration, probably by promoting the polarization of macrophages from the M1 phenotype to the M2 phenotype.

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 β (C/EBPβ), 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/EBPβ through its C-terminal helix-turn-helix domain, required for LCoR's inhibitory effects on adipogenesis. LCoR overexpression also inhibited C/EBPβ 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/EBPβ 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/EBPβ-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/EBPβ transcriptional activity and add LCoR to the growing list of transcriptional corepressors of adipogenesis.

This work aims to design and fabricate sub-wavelength structures on lithium triborate surface for increasing its transmittance at 1064 nm. The finite-difference time-domain (FDTD) method is used to discuss the effects of subwavelength structure parameters such as period, depth, duty cycle and shape factor on the reflectivity. The subwavelength surface microstructures are fabricated by interference lithography technique and reactive ion beam etching method. The transmittance of the lithium triborate with single-side sub-wavelength structures is measured by UVvisible- near-infrared spectrophotometer. The results show that the transmittance of the sample with single-side microstructures at 1064 nm is about 4% higher than that of the polished substrate.

In a previous study, the temperature-rise of a spectral beam combining grating was analyzed theoretically and experimentally. It was concluded that the temperature of a grating can be effectively reduced by increasing the substrate thickness or by using a substrate material with higher thermal conductivity. In this study, yttrium aluminum garnet (YAG) was used as the substrate material to fabricate a spectral beam combining grating. The temperature, distortion, and far-field beam quality of the YAG-substrate-grating were analyzed theoretically and experimentally. It is concluded that, compared with the traditional quartz-substrate-grating, not only can the YAG-substrate-MDG withstand higher power, but the beam quality of the diffraction laser is also better.

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.

A new 800nm center-wavelength metal dielectric grating with all SiO2 grating structures is designed and tested, which has a high laser damage threshold of 0.40J/cm2 on grating surface at pulse duration of 32fs.

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 V O 2 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 V O 2 film on the surface electric field and the − 1 diffraction efficiency of the MDG and presents a specific example of using V O 2 film to test high reflector temperature. The study concludes that V O 2 film is a feasible method of measuring temperature and better than an infrared thermal imager.

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., Author summary The functional brown adipose tissue (BAT) identified in human adults consists of not only classic brown adipocytes but also brown-like adipocytes (beige adipocytes), both of which are important for energy homeostasis. Due to the same ability to convert fat into heat as brown adipocytes, beige adipocytes have been considered as a novel pharmacological target to combat obesity. Growing evidence suggests that promoting the development and formation of beige adipocytes in white adipose tissue (WAT), also called the browning of WAT, is able to prevent diet-induced obesity and improve metabolism in rodents. Thus, understanding the molecular basis for the regulation of browning in WAT may help us to develop new strategies to counteract obesity and metabolic diseases. In this study, adipocyte-specific p38α knockout (Fp38αKO) mice are generated that display a lean phenotype, improved metabolism, and resistance to diet-induced obesity. Interestingly, we found that adipocyte p38α deficiency facilitates the browning in WAT. Then, we show that pharmaceutical inhibition of p38α enhances the browning in WAT and has metabolic benefits. We propose that inhibiting p38α in WAT, possibly combined with cold exposure, could constitute an exciting pharmacological target to combat obesity and metabolic diseases.

Nonalcoholic fatty liver disease (NAFLD) is tightly associated with insulin resistance, type 2 diabetes, and obesity. As the defining feature of NAFLD, hepatic steatosis develops as a consequence of metabolic dysregulation of de novo lipogenesis, fatty acid uptake, fatty acid oxidation, and triglycerides (TG) export. MicroRNAs (miRNAs), a class of endogenous small noncoding RNAs, play critical roles in various biological processes through regulating gene expression at post-transcriptional level. A growing body of evidence suggests that miRNAs not only maintain hepatic TG homeostasis under physiological condition, but also participate in the pathogenesis of NAFLD. In this review, we focus on the current knowledge of the hepatic miRNAs associated with the development of liver steatosis and the regulatory mechanisms involved, which might be helpful to further understand the nature of NAFLD and provide a sound scientific basis for the drug development.

A modal method for designing the one-dimensional (1-D) dielectric multilevel antireflection gratings (ARGs) used for TE polarized waves is proposed based on the effective refractive indices concept of the modal method (MM). In this method, the effective refractive index (ERI) for each level is determined by the effective mode index of the modal method. The refractive indices under and above the grating region are equivalent to their effective refractive indices that is determined by the 0th order propagating wave vector of the Fourier expansion of the electric fields under and above the grating region, which are different from the conventional effective medium theory (EMT), and the relationship between the ERI in MM and that in EMT are also revealed. As an example, we designed and analyzed the fused-silica multilevel ARGs by using the MM and the commonly used second-order effective medium theory (SEMT). The designed results are numerically verified by using the rigorous coupled-wave analysis method (RCWA) and the thin-film theory.

The spectrum selective absorption effect in grating-based devices is studied. A TE polarization spectrum selective absorber exhibiting near 100% absorption at the resonant wavelength is investigated for infrared frequencies. A qualitative physical understanding of such perfect selective absorption effect is illustrated by investigating the electric field distributions and time-averaged power loss density. The influences of structure parameters on the absorption spectrum are studied in detail. Based on the study above, two multi-band absorbers with the vertically cascaded metal-dielectric grating structures are designed and investigated. The principle of such perfect absorption effects is attributed to guided mode resonance in different dielectric spacer layers. The designed absorber can be used in sub-diffraction-scale infrared pixels, high quality sensors and thermal emitters.

A surface plasmon resonance (SPR) based graphene sensor for infrared wavelength is presented. It consists of a graphene ribbon array on top of a quartz substrate. The refractive index changes above the sensor surface, which is due to the appearance of gas or the absorption of biomolecules, can be detected by measuring the resulting spectral shifts of the resonant transmission dip. The dynamic tunability of graphene enables the detectable refractive index changes covering a broadband wavelength range. The influence of Fermi level and the number of graphene layers on the performance of sensor are investigated in details, which should be useful for guiding the design of sensors based on a graphene ribbon array. The sensor can be used for sensing both gas and low-refractive-index materials in an aqueous environment.

The spectrum selective absorption effect of a vertically cascaded metal-dielectric grating structure is studied. A polarization-independent spectrum selective absorber based on two pairs of stacked metal-dielectric grating structures is presented for the infrared frequencies. The near-unity absorption with polarization independence is observed under normal incidence. The understanding of such a perfect selective absorption mechanism is illustrated by investigating the electric field distributions and power loss density at the resonant wavelength. The angle independence is also studied for this absorber and it is found that the absorber can maintain high absorbance around large incident angle range (0° -33° ), especially for the TM polarization.

We report on the development of metal dielectric gratings (MDG) including two layers of gold film and a silica layer, which is simple and has enough broadband with 105 nm over 90%. The measured laser-induced damage threshold (LIDT) on the grating surface is 0.40 J/cm2 at a pulse duration of 32 fs, which is twice more than that of gold gratings, and the initial damage comes from nodule defects. Laser-induced ionization theory is first used to study the effect of nodule defects on LIDT of MDG and predict the maximum LIDT of the perfect MDG. The prediction value of the MDG without nodule defects is 0.60 J/cm2 on the grating surface, which has tremendous application potential in petawatt-class laser systems.

The absorption effect in grating-based devices is theoretically investigated. Three kinds of spectrum selective absorbers (TE polarization, TM polarization and polarization-independent) exhibiting near-unity absorption at the resonant wavelength are studied at visible frequencies. The optimized parameters of absorbers are all obtained by use of rigorous coupled-wave analysis and the simulated annealing algorithm. The underlying physics understanding of such perfect absorption effects is illustrated by investigating the field distributions and power loss density in these absorbers. The enhancement of absorption is attributed to the hybridization of cavity mode and guide mode resonance for TE polarization absorber, and attributed to the surface plasmon resonance for TM polarization absorber with ultra-thin grating structure. The relationship between the absorption spectrum and the geometric parameters of the structures is studied. In order to achieve perfect absorption, the grating should have large thickness for TE polarization, while it has not strict restriction for TM polarization. The conclusions should be useful for designing a polarization-dependent or -independent selective absorber based on a metallic grating structure in the visible region.

A rectangular-groove metal-dielectric reflective grating is designed, which includes the inner metal films and the outside dielectric film for achieving high diffraction efficiency at the -1st order with wideband low enhancement of electric field intensity inside the grating. By using rigorous coupled-wave analysis (RCWA) and simulated annealing algorithm, an optimized grating with diffraction efficiency exceeding 95% over 26 nm wavelength bandwidth and the maximum enhancement of electric field intensity in solid material less than 1.2 over 70 nm wavelength bandwidth is obtained. The optimized metal-dielectric reflective grating should be useful in the applications of high-power femtosecond laser system.

A broadband polarizing beam splitter (PBS) with metal-wire nanograting in near infrared region is designed and analyzed. The grating profiles are optimized by use of rigorous coupled-wave analysis (RCWA) and the simulated annealing (SA) algorithm. Based on the optimized structure, high polarization efficiency, high extinction ratio and large angular tolerance with a broad wavelength range (1–3 μm) are obtained. Both of the transmission efficiencies of TM-polarization and reflection efficiencies of TE-polarization are over 95%. The extinction ratio of transmittance and reflectance are over 25 dB and 16 dB in the 1–3 μm wavelength range, respectively. At the same time, as a comparison we also design a PBS with double-groove metal-wire nanograting, the grating has two grooves per period, which is different from conventional gratings. The PBS also has large angular tolerance, which is −40° to 40°. The designed grating can be used in optical communication and infrared imaging polarimetry.

A simplified modal method to explain the resonance phenomenon in guided mode resonance (GMR) gratings with asymmetric coatings is presented. The resonance observed is due to the interaction of two propagation modes inside the grating. The reflectivity spectra and electric field distributions calculated from the simplified modal method are compared using rigorous coupled-wave analysis (RCWA). The influences of high-order evanescent modes on the resonance peak are analyzed. A matrix Fabry-Perot (FP) resonance condition is developed to evaluate the resonance wavelength. An explanation for the resonance phenomenon observed based on the FP resonance phase condition is also proposed and demonstrated. The simplified method provides clear physical insights into GMR gratings that are useful for the analysis of a variety of other resonance gratings.

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.

Generation of longitudinally polarized focusing twin Bessel beams in focal region of a high numerical aperture ( NA ) objective is described based on circular Dammann gratings for radially polarized Bessel–Gauss input fields. Numerical simulations show that, under focusing of an objective of NA =0.95, the depth of focus (DOF) of the focused twin Bessel beams can reach as long as tens or even ∼10 2 of wavelengths while its average transverse spot over the whole range of the DOF is kept subdiffration-limited. At the same time, the longitudinal polarization purity in focus volume is higher than 90% for the central lobe. Therefore, this tightly focused non-diffracting field should be of great interest for applications in numerous areas, such as particle acceleration and manipulation, micromachining, second-harmonic generation, Raman spectroscopy, etc.

We present a unified design of wavelength-independent deep-etched fused-silica gratings as polarizing beam splitters and polarization-independent two-port beam splitters by using the simplified modal method. By defining unified grating parameters as the ratio of incident wavelength to grating period and the ratio of groove depth to grating period, unified grating structures are found to be approximately wavelength-independent, which is based on the modal view of the accumulated phase difference of two excited propagating grating modes. Diffraction efficiencies given by the rigorous coupled-wave analysis (RCWA) verified this unified design at the wavelength of 1064 nm. It should be noted that this unified design of wavelength-independent gratings is an analytic result, which is impossible to be derived with the well-known numerical RCWA. Modal method is powerful and presents a clear physical picture for us to obtain this unified design. Therefore, this unified design can be used as a general guideline for designing deep-etched fused-silica gratings as beam splitters for practical applications from ultraviolet to near infrared.

We theoretically investigated the design of polarizing beam splitters (PBS) of two-layer dielectric rectangular transmission gratings in Littrow mounting. The PBS grating is aimed to separate TE and TM polarized waves into two different transmitted orders, i.e. the 0th and −1st orders. The polarization-dependent diffraction process is analyzed by using a simplified modal method. The mode reflection and transmission at the interface of the two layers are illustrated. Design equations are given based on the average mode indices of the even and odd modes inside the grating region, which are verified by using rigorous coupled wave analysis. Moreover, with simulated annealing algorithm, two kinds of two-layer PBS gratings are optimized for operation over the C-band (1520–1570 nm). Compared with the single-layer transmission PBS gratings, such two-layer scheme exhibits a great flexibility of design. The PBSs of two-layer dielectric transmission gratings should be useful for practical applications.

SummaryUnderstanding the fiber-type specification and metabolic switch in skeletal muscle provides insights into energy metabolism in physiology and diseases. Here, we show that miR-182 is highly expressed in fast-twitch muscle and negatively correlates with blood glucose level. miR-182 knockout mice display muscle loss, fast-to-slow fiber-type switching, and impaired glucose metabolism. Mechanistic studies reveal that miR-182 modulates glucose utilization in muscle by targeting FoxO1 and PDK4, which control fuel selection via the pyruvate dehydrogenase complex (PDHC). Short-term high-fat diet (HFD) feeding reduces muscle miR-182 levels by tumor necrosis factor α (TNFα), which contributes to the upregulation of FoxO1/PDK4. Restoration of miR-182 expression in HFD-fed mice induces a faster muscle phenotype, decreases muscle FoxO1/PDK4 levels, and improves glucose metabolism. Together, our work establishes miR-182 as a critical regulator that confers robust and precise controls on fuel usage and glucose homeostasis. Our study suggests that a metabolic shift toward a faster and more glycolytic phenotype is beneficial for glucose control.

Nonalcoholic fatty liver disease (NAFLD) is tightly associated with insulin resistance, type 2 diabetes, and obesity. As the defining feature of NAFLD, hepatic steatosis develops as a consequence of metabolic dysregulation of de novo lipogenesis, fatty acid uptake, fatty acid oxidation, and triglycerides (TG) export. MicroRNAs (miRNAs), a class of endogenous small noncoding RNAs, play critical roles in various biological processes through regulating gene expression at post-transcriptional level. A growing body of evidence suggests that miRNAs not only maintain hepatic TG homeostasis under physiological condition, but also participate in the pathogenesis of NAFLD. In this review, we focus on the current knowledge of the hepatic miRNAs associated with the development of liver steatosis and the regulatory mechanisms involved, which might be helpful to further understand the nature of NAFLD and provide a sound scientific basis for the drug development.

we present the simplified modal method for the holographic grating, which is a physical insight method. The difficult diffraction process can be vividly interpreted by this simple method.

Understanding the regulation of insulin signalling in tissues provides insights into carbohydrate and lipid metabolism in physiology and disease. Here we show that hepatic miR-378/378* expression changes in response to fasting and refeeding in mice. Mice overexpressing hepatic miR-378/378* exhibit pure hepatic insulin resistance. miR-378 inhibits hepatic insulin signalling through targeting p110α, a subunit of PI3K and hence a critical component of insulin signalling. Knockdown of hepatic p110α mimics the effect of miR-378, while restoration of p110α expression abolishes the action of miR-378 on insulin signalling as well as its systemic effects on glucose and lipid homeostasis. miR-378/378* knockout mice display hypoglycemia and increased hepatic triglyceride level with enhanced insulin sensitivity. Inhibition of hepatic p110α in miR-378/378* knockout mice corrects the abnormal glucose tolerance. Finally, we show that overexpression of hepatic miR-378/378* ameliorates hepatic steatosis in ob/ob mice without exacerbating hyperglycemia. Our findings establish fasting-responsive miR-378 as a critical regulator of hepatic insulin signalling.

We present a grating imaging scanning lithography system for the fabrication of large-sized gratings. In this technology, +(-)1-order diffractive beams are generated by a phase grating and selected by a spatial filter. Meanwhile, a 4f system enables the +(-)1-order diffractive beams to form a grating image with a clear jagged-edge boundary on the substrate. A high-precision two-dimensional (2D) mobile stage is used for complementary cyclical scanning, thereby effectively eliminating image stitching errors. The absence of such errors results in a seamless and uniform large-sized grating. Characterized by a simple structure, high energy use, and good stability, this lithography system is highly relevant to the high-speed and cost-effective production of large-sized gratings.

This paper will report our recent works on fabrication, evaluation, and applications of gratings. We are using the Dammann parallel laser writing facility for fabrication of gratings. High-efficiency reflective gratings and large-sized grating are fabricated. We have fabricated high-power reflective laser vortex grating with expectation of a new laser drilling effect for laser fusion in the future, which is just evaluated by our developed method. These gratings are essential elements for high-power laser systems and other high-demanding metrology applications.

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.

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 β-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.

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.

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.

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.

Although there are several well -known methods such as RCWA, FMM, for analyzing the diffraction properties of gratings, design of these optical elements with specified spectral properties is commonly a challenging problem. It is relatively not easy for the researchers to design narrow line-with diffraction filters based on guided mode resonance phenomenon with common diffraction algorithm. Simulated Annealing (SA) method is evolutionary, robust technique that has been widely utilized to design optical diffraction components. This method is inspired by the physical process of heating and controlled cooling of metal material to increase the size of its crystals and reduce their defects. The most distinctive features of this method lie in its powerful ability of convergence towards the global minimum in a reasonable computation time and the independence of the initial parameter values. In this paper, first, the physical basis of SA and its mathematical realization are introduced. Then, a Guided-Mode Resonant Grating (GMRG) filters with single layer is designed by using SA algorithm. The central wavelength of GMRG filter is locked at 532nm and its line-width is fixed at 1nm. The plane wave light radiates the grating from air cover with normal incidence. The optimized parameters are refractive indices and thicknesses of high and low material of grating, other parameters are grating period and fill factor of the grating. It is shown from our calculation that an excellent reflection spectrum with narrow line-width, high peak and low sideband can be obtained after optimizing the grating parameters. Next, a double layered GMRG filter with line-width of 4nm, which is relatively easy fabrication in experiment, is designed at central wavelength of 1064nm. The optimized parameters are grating period, groove depth, refractive index of waveguide layer and fill factor respectively. The grating substrate and waveguide layer are Sio2 and Hfo2 respectively, the grating structure is directly etched on the waveguide layer. The above grating values should be included in reasonable ranges in consideration of grating fabrication in our experiment condition. It is demonstrated from the calculations with the parameters obtained from SA optimization algorithm that the peak diffraction efficiency is more than 99% at central wavelength 1064nm and the sideband reflection is depressed at the level bellow 5% in a large wavelength range. Moreover, the parameters of a triple layer GMRG filter structure are also provided with this powerful method. Meanwhile, the results found by SA method are compared with RCWA theory.

Double femtosecond laser pulses are usually generated by using a Michelson structure. We propose a novel and simple device by using two high-density transmissive gratings for generation of double pulses and conversion between single and double laser pulses by shifting one of the two gratings by a quarter period. The apparatus has the advantages of compact volume, simple structure, and convenience in manipulation. Experimental outputs of the double laser pulses are well verified in experiment, which can be properly explained by numerical simulation with the rigorous coupled-wave theory. This structure provides an interesting approach for generation of double pulses and conversion between single and double laser pulses for practical applications of the femtosecond laser.

We investigated the use of Au wire-grid as the high efficient polarizing beam splitter (PBS). To achieve high extinction ratio and diffraction efficiency, the grating depth and period are optimized by using the rigorous coupled-wave analysis (RCWA).