Knockout of lws1 in zebrafish (Danio rerio) reveals its role in regulating feeding and vision-guided behavior.

Long-wave sensitive (LWS) is a G protein-coupled receptor expressed in the retina, and zebrafish is a better model organism for studying vision, but the role of LWS1 in vision-guided behavior of larvae fish has rarely been reported. In this study, we found that zebrafish lws1 and lws2 are tandemly replicated genes, both with six exons, with lws1 being more evolutionarily conserved. The presence of Y277F in the amino acid sequence of lws2 may have contributed to the shift of λmax to green light. We established a lws1 knockout zebrafish model using CRISPR/Cas9 technology. Lws1-/- larvae showed significantly higher levels of feeding and appetite gene (agrp) expression than WT, and significantly lower levels of anorexia gene (pomc, cart) expression. In addition, green light gene compensation was observed in lws1-/- larvae with significantly increased expression levels of rh2-1. The light-dark movement test showed that lws1-/- larvae were more active under light-dark transitions or vibrational stimuli, and the expression of phototransduction-related genes was significantly up-regulated. This study reveals the important role of lws1 gene in the regulation of vision-guided behavior in larvae.

Regulatory effect of NK homeobox 1 (NKX2.1) on melanocortin 4 receptor (Mc4r) promoter in Mandarin fish.

The melanocortin 4 receptor (MC4R) is a G protein-coupled transporter that mediates the regulation of thyroid hormones and leptin on energy balance and food intake. However, the mechanisms of transcriptional regulation of Mc4r by thyroid hormone and leptin in fish have been rarely reported. The messenger RNA expression of Mc4r gene was significantly higher in brain than those in other tissues of mandarin fish. We analyzed the structure and function of a 2029 bp sequence of Mc4r promoter. Meanwhile, overexpression of NKX2.1 and incubation with leptin significantly increased Mc4r promoter activity, but triiodothyronine showed the opposite effect. In addition, mutations in the NKX2.1 binding site abolished not only the activation of Mc4r promoter activity by leptin but also the inhibitory effect of thyroid hormones on Mc4r promoter activity. In summary, these results suggested that thyroid hormones and leptin might regulate the transcriptional expression of Mc4r through NKX2.1.

Direct Observation of Fractal-Dimensional Percolation in the 3D Cluster Dynamics of a Ferroelectric Supercrystal.

We perform percolation analysis of crossed-polarizer transmission images in a biased nanodisordered bulk KTN:Li perovskite. Two distinct percolative transitions are identified at two electric field thresholds. The low-field transition involves a directional fractal chain of dimension D=1.65, while the high-field transition has a dimension D>2. Direct cluster imaging in the volume is achieved using high-resolution orthographic 3D projections based on giant refraction. Percolation is attributed to a full-3D domain reorientation that mediates the transition from a ferroelectric supercrystal state to a disordered domain mosaic.

Evidence of Chaotic Dynamics in Three-Soliton Collisions.

We observe chaotic optical wave dynamics characterized by erratic energy transfer and soliton annihilation and creation in the aftermath of a three-soliton collision in a photorefractive crystal. Irregular dynamics are found to be mediated by the nonlinear Raman effect, a coherent interaction that leads to nonreciprocal soliton energy exchange. Results extend the analogy between solitons and particles to the emergence of chaos in three-body physics and provide new insight into the origin of the irregular dynamics that accompany extreme and rogue waves.

Soliton Maxwell demons and long-tailed statistics in fluctuating optical fields.

We demonstrate experimentally in biased photorefractive crystals that collisions between random-amplitude optical spatial solitons produce long-tailed statistics from input Gaussian fluctuations. The effect is mediated by Raman nonlocal corrections to Kerr self-focusing that turn soliton-soliton interaction into a Maxwell demon for the output wave amplitude.

Observation of polarization-maintaining light propagation in depoled compositionally disordered ferroelectrics.

We investigate the evolution of the state of polarization of light propagating through bulk depoled composite ferroelectrics below the Curie temperature. In contrast to standard depoled ferroelectrics, where random birefringence causes depolarization and scattering, light is observed to suffer varying degrees of depolarization and remains fully polarized when linearly polarized along the crystal principal axes. The effect is found to be supported by the formation of polarized speckles organized into a spatial lattice and occurs as the ferroelectric settles into a spontaneous super-crystal, a three-dimensional coherent mosaic of ferroelectric clusters. The polarization lattices gradually disappear as the ferroelectric state reduces to a disordered distribution of polar nanoregions above the critical point.

PCSK9 inhibition-mediated reduction in Lp(a) with evolocumab: an analysis of 10 clinical trials and the LDL receptor's role.

Lipoprotein (a) [Lp(a)] is independently associated with CVD risk. Evolocumab, a monoclonal antibody (mAb) to proprotein convertase subtilisin/kexin type 9 (PCSK9), decreases Lp(a). The potential mechanisms were assessed. A pooled analysis of Lp(a) and LDL cholesterol (LDL-C) in 3,278 patients from 10 clinical trials (eight phase 2/3; two extensions) was conducted. Within each parent study, biweekly and monthly doses of evolocumab statistically significantly reduced Lp(a) at week 12 versus control (P < 0.001 within each study); pooled median (quartile 1, quartile 3) percent reductions were 24.7% (40.0, 3.6) and 21.7% (39.9, 4.2), respectively. Reductions were maintained through week 52 of the open-label extension, and correlated with LDL-C reductions [with and without correction for Lp(a)-cholesterol] at both time points (P < 0.0001). The effect of LDL and LDL receptor (LDLR) availability on Lp(a) cell-association was measured in HepG2 cells: cell-associated LDL fluorescence was reversed by unlabeled LDL and Lp(a). Lp(a) cell-association was reduced by coincubation with LDL and PCSK9 and reversed by adding PCSK9 mAb. These studies support that reductions in Lp(a) with PCSK9 inhibition are partly due to increased LDLR-mediated uptake. In most situations, Lp(a) appears to compete poorly with LDL for LDLR binding and internalization, but when LDLR expression is increased with evolocumab, particularly in the setting of low circulating LDL, Lp(a) is reduced.

Turbulent Transitions in Optical Wave Propagation.

We report the direct observation of the onset of turbulence in propagating one-dimensional optical waves. The transition occurs as the disordered hosting material passes from being linear to one with extreme nonlinearity. As the response grows, increased wave interaction causes a modulational unstable quasihomogeneous flow to be superseded by a chaotic and spatially incoherent one. Statistical analysis of high-resolution wave behavior in the turbulent regime unveils the emergence of concomitant rogue waves. The transition, observed in a photorefractive ferroelectric crystal, introduces a new and rich experimental setting for the study of optical wave turbulence and information transport in conditions dominated by large fluctuations and extreme nonlinearity.

Intrinsic Negative Mass from Nonlinearity.

We propose and provide experimental evidence of a mechanism able to support negative intrinsic effective mass. The idea is to use a shape-sensitive nonlinearity to change the sign of the mass in the leading linear propagation equation. Intrinsic negative-mass dynamics is reported for light beams in a ferroelectric crystal substrate, where the diffusive photorefractive nonlinearity leads to a negative-mass Schrödinger equation. The signature of inverted dynamics is the observation of beams repelled from strongly guiding integrated waveguides irrespective of wavelength and intensity and suggests shape-sensitive nonlinearity as a basic mechanism leading to intrinsic negative mass.

Volume integrated phase modulator based on funnel waveguides for reconfigurable miniaturized optical circuits.

We demonstrate the integration of a miniaturized 30(x) µm×30(y) µm×2.7(z) mm electro-optic phase modulator operating in the near-IR (λ=980 nm) based on the electro-activation of a funnel waveguide inside a paraelectric sample of photorefractive potassium lithium tantalate niobate. The modulator forms a basic tassel in the realization of miniaturized reconfigurable optical circuits embedded in a single solid-state three-dimensional chip.

Spatial Rogue Waves in Photorefractive Ferroelectrics.

Rogue waves are observed as light propagates in the extreme nonlinear regime that occurs when a photorefractive ferroelectric crystal is undergoing a structural phase transition. The transmitted spatial light distribution contains bright localized spots of anomalously large intensity that follow a signature long-tail statistics that disappears as the nonlinearity is weakened. The isolated wave events form as out-of-equilibrium response and disorder enhance the Kerr-saturated nonlinearity at the critical point. Self-similarity associable to the individual observed filaments and numerical simulations of the generalized nonlinear Schrödinger equation suggests that dynamics of soliton fusions and scale invariance can microscopically play an important role in the observed rogue intensities and statistics.

Continuous Solitons in a Lattice Nonlinearity.

We study theoretically and experimentally the propagation of optical solitons in a lattice nonlinearity, a periodic pattern that both affects and is strongly affected by the wave. Observations are carried out using spatial photorefractive solitons in a volume microstructured crystal with a built-in oscillating low-frequency dielectric constant. The pattern causes an oscillating electro-optic response that induces a periodic optical nonlinearity. On-axis results in potassium-lithium-tantalate-niobate indicate the appearance of effective continuous saturated-Kerr solitons, where all spatial traces of the lattice vanish, independently of the ratio between beam width and lattice constant. Decoupling the lattice nonlinearity allows the detection of discrete delocalized and localized light distributions, demonstrating that the continuous solitons form out of the combined compensation of diffraction and of the underlying periodic volume pattern.

PCSK9 inhibition fails to alter hepatic LDLR, circulating cholesterol, and atherosclerosis in the absence of ApoE.

LDL cholesterol (LDL-C) contributes to coronary heart disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases LDL-C by inhibiting LDL-C clearance. The therapeutic potential for PCSK9 inhibitors is highlighted by the fact that PCSK9 loss-of-function carriers exhibit 15-30% lower circulating LDL-C and a disproportionately lower risk (47-88%) of experiencing a cardiovascular event. Here, we utilized pcsk9(-/-) mice and an anti-PCSK9 antibody to study the role of the LDL receptor (LDLR) and ApoE in PCSK9-mediated regulation of plasma cholesterol and atherosclerotic lesion development. We found that circulating cholesterol and atherosclerotic lesions were minimally modified in pcsk9(-/-) mice on either an LDLR- or ApoE-deficient background. Acute administration of an anti-PCSK9 antibody did not reduce circulating cholesterol in an ApoE-deficient background, but did reduce circulating cholesterol (-45%) and TGs (-36%) in APOE*3Leiden.cholesteryl ester transfer protein (CETP) mice, which contain mouse ApoE, human mutant APOE3*Leiden, and a functional LDLR. Chronic anti-PCSK9 antibody treatment in APOE*3Leiden.CETP mice resulted in a significant reduction in atherosclerotic lesion area (-91%) and reduced lesion complexity. Taken together, these results indicate that both LDLR and ApoE are required for PCSK9 inhibitor-mediated reductions in atherosclerosis, as both are needed to increase hepatic LDLR expression.

Anti-diffracting beams through the diffusive optical nonlinearity.

Anti-diffraction is a theoretically predicted nonlinear optical phenomenon that occurs when a light beam spontaneously focalizes independently of its intensity. We observe anti-diffracting beams supported by the peak-intensity-independent diffusive nonlinearity that are able to shrink below their diffraction-limited size in photorefractive lithium-enriched potassium-tantalate-niobate (KTN:Li).

Photorefractive light needles in glassy nanodisordered KNTN.

We study the formation of 2D self-trapped beams in nanodisordered potassium-sodium-tantalate-niobate (KNTN) cooled below the dynamic glass transition. Supercooling is shown to accelerate the photorefractive response and enhance steady-state anisotropy. Effects in the excited state are attributed to the anomalous slim-loop polarization curve typical of relaxors dominated by non-interacting polar-nano-regions.

Aging solitons in photorefractive dipolar glasses.

We study experimentally the aging of optical spatial solitons in a dipolar glass hosted by a nanodisordered sample of photorefractive potassium-sodium-tantalate-niobate (KNTN). As the system ages, the waves erratically explore varying strengths of the nonlinear response, causing them to break up and scatter. We show that this process can still lead to solitons, but in a generalized form for which the changing response is compensated by changing the normalized wave size and intensity so as to maintain fixed the optical waveform.

[Comparison of efficacy for laryngeal mask airway-Supreme(TM) versus common laryngeal mask airway in children].

OBJECTIVE: To compare the efficacy of laryngeal mask airway-Supreme(TM) versus common laryngeal mask airway in children with general anesthesia. METHODS: With local research ethics committee's approval and written informed parental consent, 100 children were randomly divided into groups L (size 2.0 common laryngeal mask airway) and S (size 2.0 laryngeal mask airway-Supreme(TM)) according to random number (n = 50 each). After anesthesia induction, a common laryngeal mask airway or laryngeal mask airway-Supreme(TM) was inserted and mechanically ventilated. Time and ease for insertion, insertion success rate, airway leak pressure, success rate and ease of disposal sputum collecting tube insertion in group S, quality of airway during anesthetic maintenance, abdominal circumference changes and complications within 24 h post-operation were measured. RESULTS: Compared with group L, abdominal circumference increased less in group S (0.90 ± 0.35 vs 0.43 ± 0.18 cm, n = 46, P < 0.01). No significant inter-group differences existed for other measurements. Disposal sputum collecting tube was successfully placed in group S(100%). CONCLUSION: In children with mechanical ventilation, laryngeal mask airway-Supreme(TM) can be effectively applied to maintain a good airway. And the incidence of gastric insufflation is lower. It is particularly useful for those requiring evacuation of gastric contents during general anesthesia.

Diffraction cancellation over multiple wavelengths in photorefractive dipolar glasses.

We report the simultaneous diffraction cancellation for beams of different wavelengths in out-of-equilibrium dipolar glass. The effect is supported by the photorefractive diffusive nonlinearity and scale-free optics, and can find application in imaging and microscopy.

Hyperbolic optics and superlensing in room-temperature KTN from self-induced k-space topological transitions.

A hyperbolic medium will transfer super-resolved optical waveforms with no distortion, support negative refraction, superlensing, and harbor nontrivial topological photonic phases. Evidence of hyperbolic effects is found in periodic and resonant systems for weakly diffracting beams, in metasurfaces, and even naturally in layered systems. At present, an actual hyperbolic propagation requires the use of metamaterials, a solution that is accompanied by constraints on wavelength, geometry, and considerable losses. We show how nonlinearity can transform a bulk KTN perovskite into a broadband 3D hyperbolic substance for visible light, manifesting negative refraction and superlensing at room-temperature. The phenomenon is a consequence of giant electro-optic response to the electric field generated by the thermal diffusion of photogenerated charges. Results open new scenarios in the exploration of enhanced light-matter interaction and in the design of broadband photonic devices.

[Primary malignant tumor of the appendix: clinicopathological analysis of 22 cases].

OBJECTIVE: To investigate the clinicopathological and immunohistochemical features of primary malignant tumor of the appendix. METHODS: The clinical data were reviewed; and histopathological and immunohistochemical features were analyzed in 22 cases with primary malignant tumor of the appendix. RESULT: In 22 cases of primary malignant tumor of the appendix, 19 cases were carcinoid and 3 were adenocarcinoma. Immunohistochemistry showed that the carcinoid was positively reacted to the neuroendocrine markers, and the adenocarcinoma was negatively reacted to the neuroendocrine markers. CONCLUSION: Immunohistochemistry is useful in diagnosis of primary malignant tumor of the appendix, a rare type of cancer.