Influence of substrate effect on near-field radiative modulator based on biaxial hyperbolic materials

Relative rotation between the emitter and receiver could effectively modulate the near-field radiative heat transfer(NFRHT)in anisotropic media.Due to the strong in-plane anisotropy,natural hyperbolic materials can be used to construct near-field radiative modulators with excellent modulation effects.However,in practical applications,natural hyperbolic materials need to be deposited on the substrate,and the influence of substrate on modulation effect has not been studied yet.In this work,we investigate the influence of substrate effect on near-field radiative modulator based onα-MoO_(3).The results show that compared to the situation without a substrate,the presence of both lossless and lossy substrate will reduce the modulation contrast(MC)for different film thicknesses.When the real or imaginary component of the substrate permittivity increases,the mismatch of hyperbolic phonon polaritons(HPPs)weakens,resulting in a reduction in MC.By reducing the real and imaginary components of substrate permittivity,the MC can be significantly improved,reaching 4.64 forε_(s)=3 at t=10 nm.This work indicates that choosing a substrate with a smaller permittivity helps to achieve a better modulation effect,and provides guidance for the application of natural hyperbolic materials in the near-field radiative modulator.

Broadband all-fiber optical phase modulator based on photo-thermal effect in a gas-filled hollow-core fiber

We report broadband all-fiber optical phase modulation based on the photo-thermal effect in a gas-filled hollow-core fiber.The phase modulation dynamics are studied by multi-physics simulation.A phase modulator is fabricated using a 5.6-cm-long anti-resonant hollow-core fiber with pure acetylene filling.It has a half-wave optical power of 289 mW at 100 kHz and an average insertion loss 0.6 dB over a broad wavelength range from 1450 to 1650 nm.The rise and fall time constants are 3.5 and 3.7μs,respectively,2–3 orders of magnitude better than the previously reported microfiber-based photo-thermal phase modulators.The gas-filled hollow-core waveguide configuration is promising for optical phase modulation from ultraviolet to mid-infrared which is challenging to achieve with solid optical fibers.

Unveiling the biological role of sphingosine-1-phosphate receptor modulators in inflammatory bowel diseases

Inflammatory bowel disease(IBD)is chronic inflammation of the gastrointestinal tract that has a high epidemiological prevalence worldwide.The increasing disease burden worldwide,lack of response to current biologic therapeutics,and treatment-related immunogenicity have led to major concerns regarding the clinical management of IBD patients and treatment efficacy.Understanding disease pathogenesis and disease-related molecular mechanisms is the most important goal in developing new and effective therapeutics.Sphingosine-1-phosphate(S1P)receptor(S1PR)modulators form a class of oral small molecule drugs currently in clinical development for IBD have shown promising effects on disease improvement.S1P is a sphingosine-derived phospholipid that acts by binding to its receptor S1PR and is involved in the regulation of several biological processes including cell survival,differentiation,migration,proliferation,immune response,and lymphocyte trafficking.T lymphocytes play an important role in regulating inflammatory responses.In inflamed IBD tissue,an imbalance between T helper(Th)and regulatory T lymphocytes and Th cytokine levels was found.The S1P/S1PR signaling axis and metabolism have been linked to inflammatory responses in IBD.S1P modulators targeting S1PRs and S1P metabolism have been developed and shown to regulate inflammatory responses by affecting lymphocyte trafficking,lymphocyte number,lymphocyte activity,cytokine production,and contributing to gut barrier function.

A review of liquid crystal spatial light modulators:devices and applications

Spatial light modulators,as dynamic flat-panel optical devices,have witnessed rapid development over the past two decades,concomitant with the advancements in micro-and opto-electronic integration technology.In particular,liquid-crystal spatial light modulator(LC-SLM)technologies have been regarded as versatile tools for generating arbitrary optical fields and tailoring all degrees of freedom beyond just phase and amplitude.These devices have gained significant interest in the nascent field of structured light in space and time,facilitated by their ease of use and real-time light manipulation,fueling both fundamental research and practical applications.Here we provide an overview of the key working principles of LC-SLMs and review the significant progress made to date in their deployment for various applications,covering topics as diverse as beam shaping and steering,holography,optical trapping and tweezers,measurement,wavefront coding,optical vortex,and quantum optics.Finally,we conclude with an outlook on the potential opportunities and technical challenges in this rapidly developing field.

Multi-Objective Optimization Analysis of Auxiliary Flux Modulator Magnetic Gear with Unequal Magnetic Poles

To enhance the output torque and minimize the torque ripple of coaxial magnetic gear(CMG),a novel auxiliary flux modulator CMG with unequal magnetic poles is proposed.This design incorporates an inner rotor with an asymmetric sector and a trapezoidal combined N-S pole structure,featuring Halbach arrays for the arrangement of permanent magnets(PMs).The outer rotor PMs adopt a Spoke-type configuration.To optimize the CMG for high output torque and low torque ripple,a sensitivity analysis is conducted to identify key size parameters that significantly influence the optimization objectives.Based on the sensitivity hierarchy of these parameters,a multi-objective optimization analysis is performed using a genetic algorithm(GA)to determine the optimal structural parameter values of the CMG.In addition,a coaxial magnetic gear(CMG)topology with 4 inner and 17 outer pole pairs is adopted,and the parametric model is established.Finally,the electromagnetic properties of the CMG are evaluated using the finite element method.The results indicate a remarkable reduction in torque ripple,specifically by 46.15%.

Waveguide-integrated optical modulators with two-dimensional materials

Waveguide-integrated optical modulators are indispensable for on-chip optical interconnects and optical computing.To cope with the ever-increasing amount of data being generated and consumed,ultrafast waveguide-integrated optical modulators with low energy consumption are highly demanded.In recent years,two-dimensional(2D)materials have attracted a lot of attention and have provided tremendous opportunities for the development of high-performance waveguide-integrated optical modulators because of their extraordinary optoelectronic properties and versatile compatibility.This paper reviews the state-of-the-art waveguide-integrated optical modulators with 2D materials,providing researchers with the developing trends in the field and allowing them to identify existing challenges and promising potential solutions.First,the concept and fundamental mechanisms of optical modulation with 2D materials are summarized.Second,a review of waveguide-integrated optical modulators employing electro-optic,all-optic,and thermo-optic effects is provided.Finally,the challenges and perspectives of waveguide-integrated modulators with 2D materials are discussed.

Hypertrophic Scar Formation and Wound Healing Modulation Fatty Acids as Modulators of Severe Scars

Scar tissue usually generates severe discomfort in the short and long term. Common symptoms include anesthetics sequelae, pruritus, joint malfunction, new wounds on the scar surface, and pain. There are several treatments for scars, like compression, topical or intralesional steroid infiltration, 5-fluorouracil, dermabrasion, and surgeries with new scar tissue. For adult patients, it is easier to choose the treatment. However, compression is commonly applied in children to prevent treatments that have adverse effects. This study reports the outcomes of 15 patients submitted to abdominoplasty, traumatic wounds and post-burn scar treatments, which showed significant changes after the continuous use of an ointment composed of petrolatum, cod liver oil, BHT, Chamomilla recutita (chamomile) oil, Helianthus annuus (sunflower) oil, and Prunus amygdalus dulcis (sweet almond) oil. As components of the stratum corneum, unsaturated fatty acids influence the cutaneous structural and immune status and permeability. They also interfere with the maturation and differentiation of the stratum corneum and inhibit the production of proinflammatory eicosanoids, reactive species (ROS and RNS), and cytokines, thereby influencing the inflammatory response and possibly wound healing. This article aims to share our experience with the regular use of an ointment in adult and pediatric patients for three months. The increase in proinflammatory cytokine production at wound sites, resulting in a noninvasive, therapeutical, and effective cutaneous wound healing and scarring modulation, may provide a physiopathological explanation for the fast improvement of scars.

Effects of estrogen receptor modulators on cytoskeletal proteins in the central nervous system

Estrogen receptor modulators are compounds of interest because of their estrogenic agonistic/antagonistic effects and tissue specificity. These compounds have many clinical applications, particularly for breast cancer treatment and osteoporosis in postmenopausal women, as well as for the treatment of climacteric symptoms. Similar to estrogens, neuroprotective effects of estrogen receptor modulators have been described in different models. However, the mechanisms of action of these compounds in the central nervous system have not been fully described. We conducted a systematic search to investigate the effects of estrogen receptor modulators in the central nervous system, focusing on the modulation of cytoskeletal proteins. We found that raloxifene, tamoxifen, and tibolone modulate some cytoskeletal proteins such as tau, microtuble-associated protein 1（MAP1）, MAP2, neurofilament 38（NF38） by different mechanisms of action and at different levels： neuronal microfilaments, intermediate filaments, and microtubule-associated proteins. Finally, we emphasize the importance of the study of these compounds in the treatment of neurodegenerative diseases since they present the benefits of estrogens without their side effects.

Organic electro-optic polymer materials and organic-based hybrid electro-optic modulators

High performance electro-optic modulator,as the key device of integrated ultra-wideband optical systems,have be-come the focus of research.Meanwhile,the organic-based hybrid electro-optic modulators,which make full use of the advant-ages of organic electro-optic(OEO)materials(e.g.high electro-optic coefficient,fast response speed,high bandwidth,easy pro-cessing/integration and low cost)have attracted considerable attention.In this paper,we introduce a series of high-perform-ance OEO materials that exhibit good properties in electro-optic activity and thermal stability.In addition,the recent progress of organic-based hybrid electro-optic devices is reviewed,including photonic crystal-organic hybrid(PCOH),silicon-organic hy-brid(SOH)and plasmonic-organic hybrid(POH)modulators.A high-performance integrated optical platform based on OEO ma-terials is a promising solution for growing high speeds and low power consumption in compact sizes.

Role of inflammasome regulation on immune modulators

Inflammatory responses are essential in eliminating harmful substrates from damaged tissue and inducing recovery.Several cytokines participate in and facilitate this response. Certain cytokines such as interleukin(IL)-1β and IL-18 are initially produced in precursor form in response to toll-like receptor(TLR) ligands and undergo maturation by inflammasomes, which are cytosolic multi-protein complexes containing nucleotide-binding oligomerization domain(NOD)-containing protein 2-like receptors(NLRs). Immune modulators targeting inflammasomes have been investigated to control inflammatory diseases such as metabolic syndrome. However, most immune modulators possessing anti-inflammasome properties attenuate production of other cytokines, which are essential for host defense. In this review, we analyzed the effect of anti-inflammasome agents on the production of cytokines which are not regulated by inflammasome and involving in initial immune responses. As a result, the infiammasome inhibitors are put into three categories: non-effector, stimulator, or inhibitor of cytokine production. Even the stimulator of cytokine production ameliorated symptoms resulting from inflammasome activation in mouse models. Thus, we suggest ideal immune modulators targeting inflammasomes in order to enhance cytokine production while inhibiting cytokine maturation.

Microglia activation,classification and microglia-mediated neuroinflammatory modulators in subarachnoid hemorrhage

Subarachnoid hemorrhage is a devastating disease with significant mortality and morbidity,despite advances in treating cerebral aneurysms.There has been recent progress in the intensive care management and monitoring of patients with subarachnoid hemorrhage,but the results remain unsatisfactory.Microglia,the resident immune cells of the brain,are increasingly recognized as playing a significant role in neurological diseases,including subarachnoid hemorrhage.In early brain injury following subarachnoid hemorrhage,microglial activation and neuroinflammation have been implicated in the development of disease complications and recovery.To understand the disease processes following subarachnoid hemorrhage,it is important to focus on the modulators of microglial activation and the pro-inflammatory/anti-inflammatory cytokines and chemokines.In this review,we summarize research on the modulators of microglia-mediated inflammation in subarachnoid hemorrhage,including transcriptome changes and the neuroinflammatory signaling pathways.We also describe the latest developments in single-cell transcriptomics for microglia and summarize advances that have been made in the transcriptome-based classification of microglia and the implications for microglial activation and neuroinflammation.

Diffractive characteristics of the liquid crystal spatial light modulator

The liquid crystal spatial light modulator （LC SLM） is very suitable for wavefront correction and optical testing and can produce a wavefront with large phase change and high accuracy. The LC SLM is composed of thousands of pixels and the pixel size and shape have effects on the diffractive characteristics of the LC SLM. This paper investigates the pixel effect on the phase of the wavefront with the scalar diffractive theory. The results show that the maximum optical path difference modulation is 41μm to produce the paraboloid wavefront with the peak to valley accuracy better than λ/10. Effects of the mismatch between the pixel and the period, and black matrix on the diffraction efficiency of the LC SLM are also analysed with the Fresnel phase lens model. The ability of the LC SLM is discussed for optical testing and wavefront correction based on the calculated results. It shows that the LC SLM can be used as a wavefront corrector and a compensator.

All-fiber optical modulator based on no-core fiber and magnetic fluid as cladding

An all-fiber optical modulator, which is composed of a piece of no-core fiber spliced between two sections of singlemode fibers and uses magnetic fluid（MF） as the cladding of the no-core fiber section, is proposed and investigated experimentally. Due to the tunable refractive index and absorption coefficient of MF, the output intensity can be modulated by controlling an applied magnetic field. The dependences of the modulator＇s temporal response on the working wavelength,the magnetic field strength（H）, and the MF＇s concentration are investigated experimentally. The results are explained qualitatively by the dynamic response process of MF under the action of a magnetic field. The findings are helpful for optimizing this kind of modulator.

Ultra-low V_(pp)and high-modulation-depth InP-based electro-optic microring modulator

A modulator is an essential building block in the integrated photonics,connecting the electrical with optical signals.The microring modulator gains much attention because of the small footprint,low drive voltage and high extinction ratio.An ultra-low V_(pp)and high-modulation-depth indium phosphide-based racetrack microring modulator is demonstrated in this paper.The proposed device mainly comprises one racetrack microring,incorporating a semiconductor amplifier,and coupling with a bus waveguide through a multimode interference coupler.Traveling wave electrodes are employed to supply bidirectional bias ports,terminating with a 50-Ω impedance.The on/off extinction ratio of the microring reaches 43.3 dB due to the delicately tuning of the gain.An 11 mV V_(pp),a maximum 42.5 dB modulation depth and a 6.6 GHz bandwidth are realized,respectively.This proposed microring modulator could enrich the functionalities and designability of the fundamental integrated devices.

Design, Synthesis and Biological Evaluation of 2-Aroyl-3-aryl-6,7-dihydro-5H-furo[3,2-g]chromen Derivatives as a Novel Series of Estrogen Receptor Modulators

Based on the principles of the bioisosterism, combination of the active substructures of selective estrogen receptor modulators which are currently therapeutic agents available for the prevention and treatment of various estrogen dependent diseases, and structural optimization, a novel series of 2-aroyl-3-aryl-6,7-dihydro-5H-furo[3,2-g]- chromen derivatives was designed as potent selective estrogen receptor modulators via molecular docking. The target compounds have been synthesized, and characterized by 1R, proton NMR, ESI-MS, elemental analysis and evaluated for their antitumor activity against human osteosarcoma U2OS-EGFP-4FI2G cell line. Some target compounds showed good inhibition effects on U2OS-EGFP-4F12G cell line and the preliminary structure-activity relationships were discussed.

Research of a fractional-turn ratio saturable pulse transformer and its application in a microsecond-range pulse modulator

As a combination device for a step-up pulse transformer and a magnetic switch,the saturable pulse transformer is widely used in pulsed-power and plasma technology.A fractional-turn ratio saturable pulse transformer is constructed and analyzed in this paper.Preliminary experimental results show that if the primary energy storage capacitors are charged to 300 V,an output voltage of about 19 kV can be obtained across the capacitor connected to the secondary windings of a fractional-tum ratio saturable pulse transformer.Theoretical and experimental results reveal that this kind of pulse transformer is not only able to integrate a step-up transformer and a magnetic switch into one device,but can also lower the saturable inductance of its secondary windings,thus leading to the relatively high step-up ratio of the pulse transformer.Meanwhile,the application of the fractional-turn ratio saturable pulse transformer in a μs range pulse modulator as a voltage step-up device and main switch is also included in this paper.The demonstrated experiments display that an output voltage with an amplitude of about 29 kV,and a 1.6 μs pulse width can be obtained across a 3500 Ω resistive load,based on a pulse modulator,if the primary energy storage capacitors are charged to 300 V.This compact fractional-turn ratio saturable pulse transformer can be applied in many other fields such as surface treatment,corona plasma generation and dielectric barrier discharge.

Combining cytochrome P-450 3A4 modulators and cyclosporine or everolimus in transplantation is successful

AIM: To describe the long term follow-up of kidney allograft recipients receiving ketoconazole with calcineurin inhibitors(CNI) alone or combined with everolimus. METHODS: This is an open-label, prospective observational clinical trial in low immunologic risk patients who, after signing an Institutional Review Board approved consent form, were included in one of two groups. The first one(n = 59) received everolimus(target blood level, 3-8 ng/m L) and the other(n = 114) azathioprine 2 mg/kg per day or mycophenolate mofetyl(MMF) 2 g/d. Both groups also received tapering steroids, the cytochrome P-450 3A4(CYP3A4) modulator, ketoconazole 50-100 mg/d, and cyclosporine with C0 targets in the everolimus group of 200-250 ng/mL in 1 mo, 100-125 ng/m L in 2 mo, and 50-65 ng/m L thereafter, and in the azathioprine or MMF group of 250-300 ng/mL in 1 mo, 200-250 ng/mL in 2 mo, 180-200 ng/m L until 3-6 mo, and 100-125 ng/mL thereafter. Clinical visits were performed monthly the first year and quarterly thereafter by treating physicians and all data was extracted by the investigators.RESULTS: The clinical characteristics of these two cohorts were similar. During the follow up(66 + 31 mo), both groups showed comparable clinical courses, but the biopsy proven acute rejection rate during the full follow-up period seemed to be lower in the everolimus group(20% vs 36%; P = 0.04). The everolimus group did not show a higher surgical complication rate thanthe other group. By the end of the follow-up period, the everolimus group tended to show a higher glomerular filtration rate. Nevertheless, we found no evidence of a consistent negative slope of the temporal allograft function estimated by the modification of the diet in renal disease formula in any of both groups. At 6 years of follow-up, the uncensored and death-censored graft survivals were 91% and 93%, and 91% and 83% in the everolimus plus cyclosporine, and cyclosporine alone groups, respectively. The addition of ketoconazole saved 80% of cyclosporine and 56% of everolimus doses. CONCLUSION: Combining CYP3A4 modulators with CNI or mammalian target of rapamycin inhibitor, in low immunological risk kidney transplant recipients is feasible, effective, safe and affordable even in the long term.

Modulators of alternative splicing as novel therapeutics in cancer

Alternative splicing(AS), the process of removing introns from pre-m RNA and re-arrangement of exons to give several types of mature transcripts, has been described more than 40 years ago. However, until recently, it has not been clear how extensive it is. Genome-wide studies have now conclusively shown that more than 90% of genes are alternatively spliced in humans. This makes AS one of the main drivers of proteomic diversity and, consequently, determinant of cellular function repertoire. Unsurprisingly, given its extent, numerous splice isoforms have been described to be associated with several dise-ases including cancer. Many of them have antagonistic functions, e.g., pro- and anti-angiogenic or pro- and anti-apoptotic. Additionally several splice factors have been recently described to have oncogene or tumour suppressors activities, like SF3B1 which is frequently mutated in myelodysplastic syndromes. Beside the implications for cancer pathogenesis, de-regulated AS is recognized as one of the novel areas of cell biology where therapeutic manipulations may be designed. This editorial discusses the possibilities of manipulation of AS for therapeutic benefit in cancer. Approaches involving the use of oligonucleotides as well as small molecule splicing modulators are presented as well as thoughts on how specificity might be accomplished in splicing therapeutics.

Bio-Inspired Microwave Modulator for High-Temperature Electromagnetic Protection,Infrared Stealth and Operating Temperature Monitoring

High-temperature electromagnetic(EM) protection materials integrated of multiple EM protection mechanisms and functions are regarded as desirable candidates for solving EM interference over a wide temperature range.In this work,a novel microwave modulator is fabricated by introducing carbonyl iron particles(CIP)/resin into channels of carbonized wood(C-wood).Innovatively,the spaced arrangement of two microwave absorbents not only achieves a synergistic enhancement of magnetic and dielectric losses,but also breaks the translational invariance of EM characteristics in the horizontal direction to obtain multiple phase discontinuities in the frequency range of 8.2-18.0 GHz achieving modulation of reflected wave radiation direction.Accordingly,CIP/C-wood microwave modulator demonstrates the maximum effective bandwidth of 5.2 GHz and the maximum EM protection efficiency over 97% with a thickness of only 1.5 mm in the temperature range 298-673 K.Besides,CIP/C-wood microwave modulator shows stable and low thermal conductivities,as well as monotonic electrical conductivity-temperature characteristics,therefore it can also achieve thermal infrared stealth and working temperature monitoring in wide temperature ranges.This work provides an inspiration for the design of high-temperature EM protection materials with multiple EM protection mechanisms and functions.

Polymer Electro-optic Modulator Linear Bias Using the Thermo-optic Effect

A quasi-rectangular waveguide polymer MacH^(-)Zehnder (M-Z) electro-optic (EO) modulator based on an organic/inorganic hybrid material with thermal bias control is fabricated and demonstrated.Linear bias for the modulator is obtained through thermo-optic effect.The optical output is adjusted by changing phase difference between the two arms of the M-Z interferometer.A power consumption of 16.1 m W for π phase change is observed owing to the application of silica cladding.This approach is proved to be effective to suppress direct current drift in polymer EO modulators.