Design of the "EAST" strategy in patients with asymptomatic intracranial atherosclerotic stenosis.

INTRODUCTION: Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and confers a high risk of stroke recurrence, despite aggressive medical therapy. Asymptomatic ICAS (aICAS) is a frequent finding on neuroimaging, and it's an independent risk factor for future stroke. Alirocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and effectively lower low-density lipoprotein cholesterol levels. We hypothesize that extra alirocumab in addition to statin therapy (EAST) could stabilize intracranial plaques in patients with aICAS. METHODS AND ANALYSIS: In this prospective, randomized, open-label, blinded end-point study, we will use high-resolution vessel-wall magnetic resonance imaging (HR-vwMRI) to evaluate the efficacy and safety of alirocumab in patients with asymptomatic ICAS. Eighty patients with aICAS (50 %-99 %) caused by unstable plaques will be assigned to the arm of alirocumab plus statin therapy, or the arm of statin therapy in a 1:1 ratio. Patients will undergo HR-vwMRI at recruitment and after 6 months. The primary outcome is changes in plaque features evaluated by HR-vwMRI after 6 months' treatment. This trial is being conducted at the first affiliated hospital of Nanjing medical university, China. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University. Written informed consents will be obtained from all participants. Study results will be published as peer-reviewed articles. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, Identifier: NCT06080256.

Ultrabroadband nonlinear enhancement of mid-infrared frequency upconversion in hyperbolic metamaterials.

Metamaterials have demonstrated significant potential for enhancing nonlinear processes at the nanoscale. The presence of narrowband hot-spots and highly inhomogeneous mode-field distributions often limit the enhancement of nonlinear interactions over larger spatial scales. This has posed a formidable challenge in achieving simultaneous enhancement across a broadband spectral range, significantly constraining the potential of photonic nanostructures in enhancing nonlinear frequency conversion. Here, we propose a broadband resonant mode matching method through near-field examinations that supports the multipole modes and enables the development of an ultrabroadband-enhanced 3-5 µm mid-infrared frequency upconversion technique utilizing a hyperbolic triangular pyramidal metasurface. The gap-plasma mode of the hyperbolic metamaterial multilayer system excites narrowly high-order resonances at near-infrared pump light wavelengths, while the slow-light effect generated by the dipoles achieves ultrabroadband near-field enhancement at mid-infrared wavelengths. The symmetry breaking of the triangular structure localizes these resonant modes at the tips, enabling mode-matched modulation at different wavelengths, and thus boosting the nonlinear frequency conversion process. Our approach provides a promising platform for metasurface-based frequency conversion techniques.

Self-assembly behavior and adhesive performance of imidazolium cation grafted cellulose nanocrystals in confined space.

Confined evaporation-induced self-assembly (C-EISA) is a powerful technique to guide disordered nanoparticles into long-range organized structures. Herein, we investigate the C-EISA behavior of 1-butyl-3-vinylimidazolium cation ([VBIm]+) grafted cellulose nanocrystals (CNC-C) in a parallel-plates confined geometry. Interestingly, CNC-C can spontaneously assemble into maze-like patterns with branch dimensions on the micrometer scale and uniformly distributed throughout the confined space, which is completely different from the lamellar self-assembly patterns of unmodified CNCs. Combining in situ observations and microscopic characterization, we speculate that the formation of maze-like patterns originates from the reduction of colloidal stability induced by the grafted imidazolium cations. The electrostatic attraction between CNC-C aggregated bundles and glass substrates acts as anchor points, thereby leading to the unstable motion of the liquid-air menisci during the inward intrusion of air. Due to the physicochemical properties and unique C-EISA behavior, the CNC-C based adhesive can maintain adhesion at temperatures of ca. 200 °C, while rapidly debonding when immersed in water, demonstrating the potential to be used as stimuli-responsive temporary or removable adhesives. Furthermore, the strategy proposed in this work for achieving CNCs patterning is also promising to be extended to other anisotropic rod-shaped nanoparticles.

Disparity in risk factors of ischemic stroke in four coastal-area hospitals in China.

Background: Currently, ischemic stroke is the leading cause of death in China. To compare regional differences of ischemic stroke, we analyzed the clinical characteristics of patients with ischemic stroke in four regionally representative hospitals in China. Methods: We conducted a retrospective study at four tertiary hospitals in east China, with regionally representative patients. The associated factors include hypertension, diabetes mellitus, coronary heart disease, hyperlipidemia and a combination of these factors. The standardized ratio (SR), estimated as the observed number divided by the expected number, computed as the sum of predicted probabilities from a multivariable logistic regression model derived using data from all other cities, was used to compare to average levels. Results: A total of 34,707 patients were included. The number of patients increased with age in all four hospitals and patients were predominantly male. The number of ischemic stroke cases with related factors increased with age, except for hyperlipidemia. There was no significant gender difference when multiple related factors existed simultaneously. Coronary heart disease had a more significant impact on ischemic stroke in Qingdao Municipal Hospital and the First Hospital of Qinhuangdao, while hyperlipidemia had a significant influence on ischemic stroke in the First Hospital of Qinhuangdao. Conclusions: At four hospitals in east China, with the increase of age, the risk factors associated with ischemic stroke increased, and the distribution of ischemic stroke-related factors showed regional differences.

Chiral Pearlescent Cellulose Nanocrystals Films with Broad-Range Tunable Optical Properties for Anti-Counterfeiting Applications.

Pearlescent materials are of technological importance in a diverse array of industries from cosmetics to premium paints; however, chiral pearlescent materials remain unexplored. Here, chiral pearlescent films with on-demand iridescence and metallic appearance are simply organized by leveraging vertical pressure to direct the self-assembly of cellulose nanocrystals. The films are formed with a bilayer planar anchored left-handed chiral nematic architecture, in which the bottom layer is featured with a vertical gradient pitch, and the top layer is featured with a uniform pitch. Simultaneous reflection of the rainbow colors and an on-demand color of left-handed polarized light with angle-dependent wavelength and polarization state accounts for the unique optical phenomenon based on experimental observation and theoretical analysis. Such chiroptical property can be readily tuned with architectural design, enabling reproducible optical appearance with high fidelity. Bringing the pearlescence, iridescence, and specular reflection together endows cellulose nanocrystal films with rich and tunable chiroptical properties that can be used for anti-counterfeiting applications. The current work marks the beginning of chiral pearlescent materials from renewable resources, while the pressure-directed self-assembly provides a step toward scalable production.

Rosiglitazone-induced PPARγ activation promotes intramuscular adipocyte adipogenesis of pig.

Intramuscular fat (IMF) positively influences various aspects of meat quality, while the subcutaneous fat (SF) has negative effect on carcass characteristics and fattening efficiency. Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of adipocyte differentiation, herein, through bioinformatic screen for the potential regulators of adipogenesis from two independent microarray datasets, we identified that PPARγ is a potentially regulator between porcine IMF and SF adipogenesis. Then we treated subcutaneous preadipocytes (SA) and intramuscular preadipocytes (IMA) of pig with RSG (1 µmol/L), and we found that RSG treatment promoted the differentiation of IMA via differentially activating PPARγ transcriptional activity. Besides, RSG treatment promoted apoptosis and lipolysis of SA. Meanwhile, by the treatment of conditioned medium, we excluded the possibility of indirect regulation of RSG from myocyte to adipocyte and proposed that AMPK may mediate the RSG-induced differential activation of PPARγ. Collectively, the RSG treatment promotes IMA adipogenesis, and advances SA lipolysis, this effect may be associated with AMPK-mediated PPARγ differential activation. Our data indicates that targeting PPARγ might be an effective strategy to promote intramuscular fat deposition while reduce subcutaneous fat mass of pig.

Complete and robust energy conversion by sum frequency generation based on invariant engineering.

An analytical method is proposed in this paper to achieve complete energy conversion in sum frequency generation based on the Lewis-Riesenfeld invariants theory. In the proposed scheme, a quasi-adiabatic single control parameter model is established, and the value of single control parameter is selected to make the initial eigenstate perfectly converted to the final eigenstate as needed. Corresponding to the nonlinear frequency conversion process, a nonlinear crystal structure is designed by inverse engineering using the optimal control theory. It is robust against perturbations of the coupling coefficient and phase mismatch, including variations in the pump intensity and crystal polarization period, and achieves almost 100% conversion efficiency at any crystal length. Theoretical simulations show that frequency conversion can be achieved in the wavelength range of 2.6 µm-3.6 µm, and the spectral bandwidth of conversion efficiency exceeds 50% and approaches 400 nm when the crystal length L = 1 mm.

Exosome-mediated regulatory mechanisms in skeletal muscle: a narrative review.

Skeletal muscle plays a paramount role in physical activity, metabolism, and energy balance, while its homeostasis is being challenged by multiple unfavorable factors such as injury, aging, or obesity. Exosomes, a subset of extracellular vesicles, are now recognized as essential mediators of intercellular communication, holding great clinical potential in the treatment of skeletal muscle diseases. Herein, we outline the recent research progress in exosomal isolation, characterization, and mechanism of action, and emphatically discuss current advances in exosomes derived from multiple organs and tissues, and engineered exosomes regarding the regulation of physiological and pathological development of skeletal muscle. These remarkable advances expand our understanding of myogenesis and muscle diseases. Meanwhile, the engineered exosome, as an endogenous nanocarrier combined with advanced design methodologies of biomolecules, will help to open up innovative therapeutic perspectives for the treatment of muscle diseases.

Gain-Assisted Giant Third-Order Nonlinearity of Epsilon-Near-Zero Multilayered Metamaterials.

We investigate the third-order nonlinear optical properties of epsilon-near-zero (ENZ) Au/dye-doped fused silica multilayered metamaterials in the visible spectral range for TM incident by using nonlocal effective medium theory at different incidence angles. The nonlocal response affects the permittivity of anisotropic metamaterials when the thickness of the layer cannot be much smaller than the incident wavelength. By doping pump dye gain material within the dielectric layer to compensate for the metal loss, the imaginary part of the effective permittivity is reduced to 10-4, and the optical nonlinear refractive index and nonlinear absorption coefficient are enhanced. The real and imaginary parts of the permittivity are simultaneously minimized when the central emission wavelength of the gain material is close to the ENZ wavelength, and the nonlinear refraction coefficient reaches the order of 10-5 cm2/W, which is five orders of magnitude larger than that of the nonlinear response of the metamaterial without the gain medium. Our results demonstrate that a smaller imaginary part of the permittivity can be obtained by doping gain materials within the dielectric layer; it offers the promise of designing metamaterials with large nonlinearity at arbitrary wavelengths.

Reconstruction of weak near-infrared images in methyl red-doped nematic liquid crystals via stochastic resonance.

We propose a near-infrared (NIR) image reconstruction method based on molecular reorientation of nematic liquid crystals (NLCs) doped with the azo-dye methyl red (MR). The signal can be recovered at the expense of noise via stochastic resonance. The numerical results show that image reconstruction based on the molecular reorientation in a magnetic field can be achieved when the input light intensity is 0.9W/cm2, this is due to the strong enhancement of the nonlinear optical response in MR doped-NLCs. The cross-correlation coefficient is increased from 0.26 to 0.54, and the maximum cross-correlation gain is 2.25. The results suggest a potential method in NIR weak optical image processing under noisy environments.

Right-to-left shunts in unexplained syncope: an age- and sex-matched case-control study.

Background: Syncope is common, but there is no clear cause for half of the patients diagnosed with syncope. Although suspected, there is limited evidence that right-to-left shunt (RLS) is related to syncope. This matched case-control study investigated the association between RLS (exposure) and unexplained syncope (outcome). Methods: Consecutive unexplained syncope cases, together with age- and gender-matched controls who did not have syncope were recruited from 2009 to 2010 in the first affiliated hospital of Nanjing Medical University. A transcranial Doppler ultrasonography bubble test was applied for the ascertainment of RLS. The degree of RLS was categorized into grades 0 to 4 according to the number of microemboli, which were no shunt, <10 microbubbles (MB), 11-25 MB, >25 MB single spots pattern, and MB in a shower/curtain pattern, respectively. Cerebral small vessel diseases (SVD), including white matter hyperintensity, lacunes, and enlarged perivascular spaces, were rated on Magnetic resonance imaging. Conditional logistic regression was used to examine the association between RLS and unexplained syncope. Results: A total of 52 cases and 52 age- and gender-matched controls were recruited. Among the 52 cases, 4 patients had a history of migraine. Among the 104 participants, 68 had no RLS; 13, 4, 7, and 12 presented with <10, 11-25, >25, and shower/curtain MB, respectively. The incidence of any RLS (Grade 1-4) was 48.1% (25/52) in cases and 21.2% (11/52) in controls (P=0.004). Conditional logistic regression showed an association between RLS and unexplained syncope [odds ratio (OR) =1.988; 95% confidence interval (CI): 1.233 to 3.205; P=0.005] adjusting for SVD burden. Further analysis revealed a large OR between severe RLS (Grade 3-4) and unexplained syncope (OR =8.699; P=0.006). Furthermore, SVD burden was shown to be associated with syncope. Conclusions: This matched case-control study showed a significant association between RLS and unexplained syncope, independent of cerebral SVD. Prospective studies are needed to confirm the causal relationship.

The Measurement of the Surface Dose in Regular and Small Radiation Therapy Fields Using Cherenkov Imaging.

Purpose: The aim of this study is to measure the output factor (OF) and profile of surface dose in regular and small radiation therapy fields using Cherenkov imaging (CI). Methods: A medical linear accelerator (linac) was employed to generate radiation fields, including regular open photon field (ROPF), regular wedge photon field (RWPF), regular electron field (REF) and small photon field (SPF). The photon beams consisted of two filter modes including flattening filter (FF) and flattening filter free (FFF). All fields were delivered to a solid water phantom. Cherenkov light was captured using a charge-coupled device system during phantom irradiation. The OF and profile of surface dose measured by CI were compared with those determined by film measurement, ionization chamber measurement and treatment planning system calculation in order to examine the feasibility of measuring surface dose OF and profile using CI. Results: The discrepancy between surface dose OF measured by CI and that determined by other methods is less than 6% in ROPFs with size less than 10 × 10 cm2, REFs with size less than 10 × 10 cm2, and SPFs except for 1 × 1 cm2 field. In the flat profile region, the discrepancy between surface dose profile measured by CI and that determined by other methods is less than 4% in REFs and less than 3% in ROPFs, RWPFs, and SPFs except for 1 × 1 cm2 field. The discrepancy of the surface dose profile is in compliance with the recommendation by IAEA TRS 430 reports. The discrepancy between field width measured by CI and that determined by film measurement is equal to or less than 2 mm, which is within the tolerance recommend by the guidelines of linac quality assurance in regular open FF photon fields, SPFs, and REFs with cone size of 10 × 10 cm2 in area. Conclusion: CI can be used to quantitatively measure the OF and profile of surface dose. It is feasible to use CI to measure the surface dose profile and field width in regular open FF photon fields and SPFs except for 1 × 1 cm2 field.

Risk factors for delayed-onset dementia after stroke or transient ischemic attack-A five-year longitudinal cohort study.

BACKGROUND: Stroke not only substantially increases the risk of incident dementia early after stroke but also the risk remains elevated years after. AIM: We aimed to determine the risk factors of dementia onset more than three to six months after stroke or transient ischemic attack. METHODS: This is a single-center prospective cohort study. We recruited consecutive subjects with stroke/transient ischemic attack without early-onset dementia. We conducted an annual neuropsychological assessment for five years. We investigated the association between baseline demographic, clinical, genetic (APOEɛ4 allele), and radiological factors as well as incident recurrent stroke with delayed-onset dementia using Cox proportional hazards models. RESULTS: In total, 1007 patients were recruited, of which 88 with early-onset dementia and 162 who lost to follow-ups were excluded. Forty-nine (6.5%) out of 757 patients have incident delayed-onset dementia. The presence of ≥3 lacunes, history of ischemic heart disease, history of ischemic stroke, and a lower baseline Hong Kong version of the Montreal Cognitive Assessment (MoCA) score were significantly associated with delayed-onset dementia. APOEɛ4 allele, medial temporal lobe atrophy, and recurrent stroke were not predictive. CONCLUSION: The presence of ≥3 lacunes, history of ischemic heart disease, history of ischemic stroke, and a lower baseline MoCA score are associated with delayed-onset dementia after stroke/transient ischemic attack.

Polarization-Independent Large Third-Order-Nonlinearity of Orthogonal Nanoantennas Coupled to an Epsilon-Near-Zero Material.

The nonlinear optical response of common materials is limited by bandwidth and energy consumption, which impedes practical application in all-optical signal processing, light detection, harmonic generation, etc. Additionally, the nonlinear performance is typically sensitive to polarization. To circumvent this constraint, we propose that orthogonal nanoantennas coupled to Al-doped zinc oxide (AZO) epsilon-near-zero (ENZ) material show a broadband (~1000 nm bandwidth) large optical nonlinearity simultaneously for two orthogonal polarization states. The absolute maximum value of the nonlinear refractive index n2 is 7.65 cm2∙GW-1, which is 4 orders of magnitude larger than that of the bare AZO film and 7 orders of magnitude larger than that of silica. The coupled structure not only realizes polarization independence and strong nonlinearity, but also allows the sign of the nonlinear response to be flexibly tailored. It provides a promising platform for the realization of ultracompact, low-power, and highly nonlinear all-optical devices on the nanoscale.

Near-infrared image recovery based on modulation instability in CdZnTe:V.

We propose a near-infrared image recovery method based on modulation instability in the photorefractive semiconductor CdZnTe:V. The formation mechanism of modulation instability in CdZnTe:V is discussed, and the theoretical gain model is derived. Theoretical results of optical image recovery at 1 µm and 1.5 µm wavelengths demonstrate that the maximum cross-correlation gain is 2.6 with a signal to noise intensity ratio of 0.1. These results suggest that our method could be one of potential aids for near-infrared imaging.

Accuracy-enhanced coherent Ising machine using the quantum adiabatic theorem.

The coherent Ising machine (CIM) implemented by degenerate optical parametric oscillator (DOPO) networks is a novel optical platform to accelerate computation of hard combinatorial optimization problems. Nevertheless, with the increase of the problem size, the probability of the machine being trapped by local minima increases exponentially. According to the quantum adiabatic theorem, a physical system will remain in its instantaneous ground state if the time-dependent Hamiltonian varies slowly enough. Here, we propose a method to help the machine partially avoid getting stuck in local minima by introducing quantum adiabatic evolution to the ground-state-search process of the CIM, which we call A-CIM. Numerical simulation results demonstrate that A-CIM can obtain improved solution accuracy in solving MAXCUT problems of vertices ranging from 10 to 2000 than CIM. The proposed machine that is based on quantum adiabatic theorem is expected to solve optimization problems more correctly.

Magneto-optically reorientation-induced image reconstruction in bulk nematic liquid crystals.

We theoretically propose the magneto-optically reorientation-induced image reconstruction in bulk nematic liquid crystals (NLCs). The underlying signals are reinforced and recovered at the expense of scattering noise under reorientation-induced self-focusing nonlinearity. The intensity perturbation gain is derived and the numerical results are presented to show the response of NLC molecules to the diffusive images. The nonlinear image recovery is influenced by the input light intensity, the magnetic field direction, and the correlation length. The results suggest an alternative approach to detect noisy images and promote the application of NLCs in image processing.

Analysis of corrected Cerenkov emission during electron radiotherapy by Monte Carlo method.

Cerenkov emission during electron radiotherapy had been emerging as a new dose assessment approach for clinical radiotherapy and could be imaged through a standard commercial camera. The purpose of this work aimed to study the accuracy of corrected Cerenkov emission method during electron radiotherapy by Monte Carlo (MC) method. GAMOS MC software was used to model the physics of electron therapy and calculated dose and Cerenkov photon distribution in water phantom. Compared to ionization chamber and diode measurement, MC simulated dose discrepancy was less than 1% in percentage depth dose (PDD) curves and less than. 2% in crossline profile curves, which was acceptable for clinical criterion. Compared to ionization chamber dose measurement, MC simulated Cerenkov discrepancy was less than 2% in crossline profile distribution, which was acceptable for clinical criterion. However, the Cerenkov PDD curves tended to overestimate the dose at the build-up region and underestimate the dose at the remaining attenuation region. After increasing the Cerenkov distribution depth to 2-3 mm, the discrepancy became well within 1% at the remaining attenuation region, which was acceptable for clinical criterion. Therefore, corrected Cerenkov emission could be used to assess PDD accuracy and crossline profile accuracy during electron radiotherapy.

Effect of fermented corn-soybean meal on carcass and meat quality of grower-finisher pigs.

The fermented feed has been identified as a potential alternative to antibiotics in feeds that markedly affects gut health and growth performance of pigs. Two recent studies performed in our laboratory investigated that the fermented corn-soybean meal (fermented feed, FF) improved the gut health of pigs. This study was conducted to determine the effect of a FF on the carcass, meat quality, muscle fatty acids profile, muscle amino acid and antioxidant ability of grower-finisher pigs. In this study, a total of 48 crossbred barrows (Duroc × Landrace × Large White) were randomly divided into 2 treatments with unfermented corn-soybean diet (Ctrl) and FF diet. Compared with control pigs fed a standard diet, the results showed that FF significantly increased the muscle colour of redness and significantly reduced muscle moisture loss rate. Furthermore, FF significantly increased the content of aromatic amino acids such as aspartic acid, glutamic acid and alanine. More importantly, FF increased monounsaturated fatty acid and polyunsaturated fatty acid content. Collectively, FF could be a promising feed strategy in improving meat quality and nutritional value in grower-finisher pig.

A Highly Selective and Sensitive Peptide-Based Fluorescent Ratio Sensor for Ag.

A fluorescence ratio sensor based on dansyl-peptide, Dansyl-Glu-Cys-Glu-Glu-Trp-NH2 (D-P5), was efficiently synthesized by Fmoc solid phase peptide synthesis. The sensor exhibits high selectivity and sensitivity for Ag+ over 16 metal ions in 100 mM sodium perchlorate and 50 mM 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid buffer solution by fluorescence resonance energy transfer. The 1:1 binding stoichiometry of the sensor and Ag+ is measured by fluorescence ratio response and the job's plot. The dissociation constant of the sensor with Ag+ was calculated to be 6.4 × 10-9 M, which indicates that the sensor has an effective binding affinity for Ag+. In addition, the limit of detection of the sensor for Ag+ was determined to be 80 nM, which also indicates that the sensor has a high sensitivity to Ag+. Result showed that the sensor is an excellent Ag+ sensor under neutral condition. Furthermore, this sensor displays good practicality for Ag+ detection in river water samples without performing tedious sample pretreatment, as well as for silver chloride detection.