Spatial Shifts of Reflected Light Beam on Hexagonal Boron Nitride/Alpha-Molybdenum Trioxide Structure.

This investigation focuses on the Goos-Hänchen (GH) and Imbert-Fedorov (IF) shifts on the surface of the uniaxial hyperbolic material hexagonal boron nitride (hBN) based on the biaxial hyperbolic material alpha-molybdenum (α-MoO3) trioxide structure, where the anisotropic axis of hBN is rotated by an angle with respect to the incident plane. The surface with the highest degree of anisotropy among the two crystals is selected in order to analyze and calculate the GH- and IF-shifts of the system, and obtain the complex beam-shift spectra. The addition of α-MoO3 substrate significantly amplified the GH shift on the system's surface, as compared to silica substrate. With the p-polarization light incident, the GH shift can reach 381.76λ0 at about 759.82 cm-1, with the s-polarization light incident, the GH shift can reach 288.84λ0 at about 906.88 cm-1, and with the c-polarization light incident, the IF shift can reach 3.76λ0 at about 751.94 cm-1. The adjustment of the IF shift, both positive and negative, as well as its asymmetric nature, can be achieved by manipulating the left and right circular polarization light and torsion angle. The aforementioned intriguing phenomena offer novel insights for the advancement of sensor technology and optical encoder design.

A high figure of merit of phonon-polariton waveguide modes with hbn/SiO2/graphene /hBN ribs waveguide in mid-infrared range.

Natural hyperbolic materials can confine electromagnetic waves at the nanoscale. In this study, we propose a waveguide design that combines a high quality factor (FOM) with low loss, utilizing hexagonal boron nitride and graphene and gold substrate. The waveguide consists of a dielectric rib with a graphene layer sandwiched between two hBN ribs. Numerical simulations demonstrate the existence of two guided modes in the proposed waveguide within the second reststrahlen band (1360.0 cm-1<ω < 1609.8 cm-1) of hBN. These modes are formed by coupling the hyperbolic phonon polariton (HPhP) of two hBN rib in the middle dielectric rib and are subsequently modulated by a graphene layer. Interestingly, we observe variations in four transmission parameters, namely effective length, figure of merit, device length, and propagation loss of the guided modes, with respect to the operation frequency and gate voltage. By optimizing the waveguide's geometry parameters and dielectric permittivity, the modal properties were analyzed. Simulation results indicate that optimizing the waveguide size parameters enables us to achieve a high FOM of 4.0 × 107. The proposed waveguide design offers a promising approach for designing tunable mid infrared range waveguides on photonic chips, and this concept can be extended to other 2D materials and hyperbolic materials.

Quizartinib inhibits necroptosis by targeting receptor-interacting serine/threonine protein kinase 1.

Systemic inflammatory response syndrome (SIRS), at least in part driven by necroptosis, is characterized by life-threatening multiple organ failure. Blocking the progression of SIRS and consequent multiple organ dysfunction is challenging. Receptor-interacting serine/threonine protein kinase 1 (RIPK1) is an important cell death and inflammatory mediator, making it a potential treatment target in several diseases. Here, using a drug repurposing approach, we show that inhibiting RIPK1 is also an effective treatment for SIRS. We performed cell-based high-throughput drug screening of an US Food and Drug Administration (FDA)-approved drug library that contains 1953 drugs to identify effective inhibitors of necroptotic cell death by SYTOX green staining. Dose-response validation of the top candidate, quizartinib, was conducted in two cell lines of HT-22 and MEFs. The effect of quizartinib on necroptosis-related proteins was evaluated using western blotting, immunoprecipitation, and an in vitro RIPK1 kinase assay. The in vivo effects of quizartinib were assessed in a murine tumor necrosis factor α (TNFα)-induced SIRS model. High-throughput screening identified quizartinib as the top "hit" in the compound library that rescued cells from necroptosis in vitro. Quizartinib inhibited necroptosis by directly inhibiting RIPK1 kinase activity and blocking downstream complex IIb formation. Furthermore, quizartinib protected mice against TNFα-induced SIRS. Quizartinib, as an FDA-approved drug with proven safety and efficacy, was repurposed for targeted inhibition of RIPK1. This work provides essential preclinical data for transferring quizartinib to the treatment of RIPK1-dependent necroptosis-induced inflammatory diseases, including SIRS.

Human FAM111A inhibits vaccinia virus replication by degrading viral protein I3 and is antagonized by poxvirus host range factor SPI-1.

Zoonotic poxviruses such as mpox virus (MPXV) continue to threaten public health safety since the eradication of smallpox. Vaccinia virus (VACV), the prototypic poxvirus used as the vaccine strain for smallpox eradication, is the best-characterized member of the poxvirus family. VACV encodes a serine protease inhibitor 1 (SPI-1) conserved in all orthopoxviruses, which has been recognized as a host range factor for modified VACV Ankara (MVA), an approved smallpox vaccine and a promising vaccine vector. FAM111A (family with sequence similarity 111 member A), a nuclear protein that regulates host DNA replication, was shown to restrict the replication of a VACV SPI-1 deletion mutant (VACV-ΔSPI-1) in human cells. Nevertheless, the detailed antiviral mechanisms of FAM111A were unresolved. Here, we show that FAM111A is a potent restriction factor for VACV-ΔSPI-1 and MVA. Deletion of FAM111A rescued the replication of MVA and VACV-ΔSPI-1 and overexpression of FAM111A significantly reduced viral DNA replication and virus titers but did not affect viral early gene expression. The antiviral effect of FAM111A necessitated its trypsin-like protease domain and DNA-binding domain but not the PCNA-interacting motif. We further identified that FAM111A translocated into the cytoplasm upon VACV infection by degrading the nuclear pore complex via its protease activity, interacted with VACV DNA-binding protein I3, and promoted I3 degradation through autophagy. Moreover, SPI-1 from VACV, MPXV, or lumpy skin disease virus was able to antagonize FAM111A by prohibiting its nuclear export. Our findings reveal the detailed mechanism by which FAM111A inhibits VACV and provide explanations for the immune evasive function of VACV SPI-1.

Spatial Multiplexed Protein Profiling of Cardiac Ischemia-Reperfusion Injury.

BACKGROUND: Reperfusion therapy is critical to myocardial salvage in the event of a myocardial infarction but is complicated by ischemia-reperfusion injury (IRI). Limited understanding of the spatial organization of cardiac cells, which governs cellular interaction and function, has hindered the search for targeted interventions minimizing the deleterious effects of IRI. METHODS: We used imaging mass cytometry to characterize the spatial distribution and dynamics of cell phenotypes and communities in the mouse left ventricle following IRI. Heart sections were collected from 12 cardiac segments (basal, mid-cavity, apical, and apex of the anterior, lateral, and inferior wall) and 8 time points (before ischemia [I-0H], and postreperfusion [R-0H, R-2H, R-6H, R-12H, R-1D, R-3D, R-7D]), and stained with 29 metal-isotope-tagged antibodies. Cell community analysis was performed on reconstructed images, and the most disease-relevant cell type and target protein were selected for intervention of IRI. RESULTS: We obtained a total of 251 multiplexed images, and identified 197 063 single cells, which were grouped into 23 distinct cell communities based on the structure of cellular neighborhoods. The cellular architecture was heterogeneous throughout the ventricular wall and exhibited swift changes following IRI. Analysis of proteins with posttranslational modifications in single cells unveiled 13 posttranslational modification intensity clusters and highlighted increased H3K9me3 (tri-methylated lysine 9 of histone H3) as a key regulatory response in endothelial cells during the middle stage of IRI. Erasing H3K9 methylation, by silencing its methyltransferase Suv39h1 or overexpressing its demethylase Kdm4d in isolated endothelial cells, attenuated cardiac dysfunction and pathological remodeling following IRI. in vitro, H3K9me3 binding significantly increased at endothelial cell function-related genes upon hypoxia, suppressing tube formation, which was rescued by inhibiting H3K9me3. CONCLUSIONS: We mapped the spatiotemporal heterogeneity of cellular phenotypes in the adult heart upon IRI, and uncovered H3K9me3 in endothelial cells as a potential therapeutic target for alleviating pathological remodeling of the heart following myocardial IRI.

Repurposing crizotinib to target RIPK1-dependent cell death.

Receptor-interacting protein kinase 1 (RIPK1) has emerged as a key regulator of cell death and inflammation, which are implicated in the pathogenesis of many inflammatory and degenerative diseases. RIPK1 is therefore a putative therapeutic target in many of these diseases. However, no pharmacological inhibitor of RIPK1-mediated cell death is currently in clinical use. Recognizing that a repurposed drug has an expedited clinical development pipeline, here we performed a high-throughput drug screen of Food and Drug Administration (FDA)-approved compounds and identified a novel use for crizotinib as an inhibitor of RIPK1-dependent cell death. Furthermore, crizotinib rescued TNF-α-induced death in mice with systemic inflammatory response syndrome. RIPK1 kinase activity was directly inhibited by crizotinib. These findings identify a new use for an established compound and are expected to accelerate drug development for RIPK1-spectrum disorders.

Unique ghost surface phonon polaritons in biaxially hyperbolic materials.

We predicted peculiar ghost surface phonon polaritons in biaxially hyperbolic materials, where the two hyperbolic principal axes lie in the plane of propagation. We took the biaxially-hyperbolic α-MoO3 as one example of the materials to numerically simulate the ghost surface phonon polaritons. We found three unique ghost surface polaritons to appear in three enclosed wavenumber-frequency regions, respectively. These ghost surface phonon polaritons have different features from the surface phonon polaritons found previously, i.e., they are some hybrid-polarization surface waves composed of two coherent evanescent branch-waves in the α-MoO3 crystal. The interference of branch-waves leads to that their Poynting vector and electromagnetic fields both exhibit the oscillation-attenuation behavior along the surface normal, or a series of rapidly attenuated fringes. We found that the in-plane hyperbolic anisotropy and low-symmetric geometry of surface are the two necessary conditions for the existence of these ghost surface polaritons.

Dysregulation of interaction between LOXhigh fibroblast and smooth muscle cells contributes to the pathogenesis of aortic dissection.

Rationale: While cell-cell interaction plays a critical role in physiology and disease, a comprehensive understanding of its dynamics in vascular homeostasis and diseases is yet absent. Methods: Here, by use of single-cell RNA-sequencing and multi-color staining, we delineate the cellular composition and spatial characterization of human aorta with or without aortic dissection (AD). Results: Scrutinization of cell subtype alterations revealed significantly changed fibroblast (FB)-smooth muscle cell (SMC) interactions in AD. Of these cellular interactions, LOXhigh fibroblast (fibroblast subtype 2, FB2) in diseased state exerted the most pronounced effects on pathological deterioration of SMCs in AD. In addition, pharmacologically targeting the BMP (bone morphogenetic protein) signaling pathway effectively suppressed FB2 state transition and reduced AD incidence in mice. Finally, COL5A1 (collagen type V alpha 1 chain), one of the secreted proteins released from FB2, was significantly higher in the plasma of AD patients than in control patients, suggesting its potential use as a biomarker for AD diagnosis. Conclusions: Our work not only identified a pivotal role of a specific FB subtype in AD progression, but also shed light on cell interaction dynamics in vascular diseases.

Spin-splitting in a reflective beam off an antiferromagnetic surface.

A linearly-polarized radiation can be considered as the superposition of two circularly-polarized components with the same propagating direction and opposite spins. We investigated the splitting between the two spin-components in the reflective beam off the antiferromagnetic surface. The gyromagnetism and surface impedance mismatch cause the difference between the spatial shifts of the two spin-components, i.e., the spin-splitting. We analytically achieved the in- and out-plane shift-expressions of either spin-component for two typical linearly-polarized incident beams (i.e., the p- and s-incidences). In the case of no gyromagnetism, we obtained very simple shift-expressions, which indicate a key role played by the gyromagnetism or the surface impedance-mismatch in spin-splitting. Based on a FeF2 crystal, the spin-splitting distance was calculated. The spin-splitting distance is much longer for the p-incidence than the s-incidence, and meanwhile the in-plane splitting distance is much larger than the out-plane one. The gyromagnetism plays a key role for the in-plane spin-splitting and the surface impedance-mismatch is a crucial factor for the out-plane spin-splitting distance. The results are useful for the manipulation of infrared radiations and infrared optical detection.

Large spatial shifts of reflective beam at the surface of graphene/hBN metamaterials.

We theoretically studied the Goos-Hänchen (GH) and Imbert-Fedorov (IF) shifts of reflective beam at the surface of graphene/hBN metamaterials. The results show that the GH-shift is significantly enhanced and also possesses the large reflectivity when the light beam is incident at the critical angle near the Brewster angle. We found that the IF-shift is the largest when the reflective beam is a special polarized-beam or the reflective coefficients satisfy the conditions |rs | = |rp | and φs - φp = 2jπ (j is an integer). By changing the chemical potential, filling ratio and tilted angle, the position and width of frequency windows obtaining the maximum values of shifts can be effectively adjusted. The large and tunable GH- and IF-shifts with the higher reflectivity provide an alternative scheme to develop new nano-optical devices.

Goos-Hänchen and Imbert-Fedorov shifts on hyperbolic crystals.

We investigated Goos-Hänchen (GH) and Imbert-Fedorov (IF) shifts on a uniaxial hyperbolic crystal, where a circularly-polarized beam was incident on the crystal from the free space. The GH- and IF-shifts were analytically obtained and numerically calculated for the hexagonal boron nitride. Our results demonstrate that the GH- and IF-shift spectra are complicated and completely different in and out the hyperbolic frequency-bands (the reststrahlen bands in the infrared region). At the critical or Brewster angle, concisely analytical expressions of GH-shift was found, which explicitly state the optical-loss dependence of GH-shift at these special angles. We found the GH-shifts are very large at the critical and Brewster angles. It is very necessary to know these effects since hyperbolic materials are usually applied in the nano- and micro-optics or technology fields.

Unusual spin and angular momentum of Dyakonov waves at the hyperbolic-material surface.

Three Dyakonov-like polaritons (DLPs) exist at the interface between a hyperbolic material (HM) and a covering medium (CM). Each DLP is a hybridized-polarization surface polariton composed of two evanescent waves on both sides of the interface. We investigated their spin and angular momentum. We analytically found that any DLP carries two spins producing mutually orthogonal spin angular-momentum (SAM) components. The spins and angular-momentum have different features on both sides of the interface, and further differences among the three DLPs are very obvious. For the interface structure formed by hexagonal boron nitride (hBN) and air, the SAM mainly distributes in the air for DLP-I, the SAM is approximately transverse to the propagating direction for DLP-II, and it is surprisingly large in the hBN for DLP-III and can reach several ten times that in the usual situation. There is the spin-k locking for every DLP, but the spin-k locking is different for different DLPs. These properties do not exist for traditional surface polaritons or ordinary evanescent waves. The above unique results can support some potential applications in the fields of nano- and micro-photonics, optoelectronics and mechanics, as well as relevant technologies.

Extraordinary reflection and refraction from natural hyperbolic materials.

The reflection and refraction were theoretically investigated for a linearly-polarized wave incident upon the surface of a naturally hyperbolic material. We proposed that this material is uniaxial and possesses two hyperbolic-frequency bands (HB-I and HB-II), whose optical axis is arbitrarily pointed. We paid our attention to reflective and refractive features in the HBs and predicted some extraordinary phenomena. The double reflection was found, where the reflective wave contains a transverse electric branch and a transverse magnetic branch with different amplitudes and phases. The asymmetry of reflection exists and the reflective coefficient abnormally decreases as the incident angle is enlarged. The double refraction inside the material means two refractive branches (the o-wave and e-wave). For the e-wave, there is a special frequency point (SP) in either HB, depending on the orientation of the optical axis. The e-wave and reflective wave exhibit completely different behaviors on the two sides of the SP. The e-wave is a normal refractive wave on the left side of the SP, but it is an evanescent wave on the right side. Its energy-flux seriously deviates from the incident plane and is highly condensed at the inner surface near the SP. It is more interesting that the energy-flux density of the e-wave in the HB-II can even be much larger than that of the incident wave and is opposite in direction on the two sides of the SP, which means an evident radiation-switching effect. The o-wave is a normal refractive wave in the HB-I, but it is an evanescent wave in the HB-II. The above results and conclusions were obtained from the hexagonal boron nitride (hBN). These unique properties may be very useful in optical or optoelectronic technology.

The Clinicopathological and Prognostic Significance of IDO1 Expression in Human Solid Tumors: Evidence from a Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme catalyzing the initial and rate-limiting steps in the kynurenine pathway, which converts tryptophan into kynurenine. Upregulation of IDO1 decreases tryptophan levels and increases the accumulation of kynurenine and its metabolites. These metabolites can affect the proliferation of T cells. Increasing evidence has shown that IDO1 is highly expressed in various cancer types and associated with poor prognosis of cancer patients. However, the results were inconsistent. METHODS: We searched the Web of Science, PubMed, Embase and Cochrane library databases to identify studies evaluating the prognostic value of IDO1 in cancer patients. Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by using fixed-effects/random-effects models. RESULTS: This systematic review and meta-analysis included 2706 patients from 24 articles. The results indicated a shorter overall survival in patients with high expression of IDO1 (hazard ratio [HR] = 2.03, 95% confidence interval [CI]: 1.56-2.63). Furthermore, disease-free survival was worse in patients with high expression of IDO1 (HR = 2.47, 95% CI: 1.46-4.20). Additionally, the pooled odds ratios (ORs) showed that increased IDO1 was significantly associated with tumor differentiation (OR = 1.81, 95% CI: 1.05-3.12), distant metastasis (OR = 1.45, 95% CI: 1.02-2.06), and poor clinical stage (OR = 1.89, 95% CI: 1.13-3.17). However, no significant correlation was observed of increased IDO1 expression with age, sex, lymph node metastasis, and tumor size. CONCLUSION: High expression of IDO1 is associated with poor clinical outcomes. IDO1 could serve as a biomarker of prognosis and a potential predictive factor of clinicopathology in various cancers. Further studies should be performed to verify the clinical utility of IDO1 in human solid tumors.

Author Correction to: Recent Perioperative Pharmacological Prevention of Acute Kidney Injury after Cardiac Surgery: A Narrative Review.

Acute kidney injury (AKI) is a common and severe complication of cardiac surgery, and related rates of both hospitalization and long-term mortality are increasing. A number of studies have explored the preventive effects of perioperative pharmacological therapy on AKI after cardiac surgery.

Correction: The optimal time of initiation of renal replacement therapy in acute kidney injury: A meta-analysis.

[This corrects the article DOI: 10.18632/oncotarget.17946.].

Correction: Aliskiren therapy in hypertension and cardiovascular disease: a systematic review and a meta-analysis.

[This corrects the article DOI: 10.18632/oncotarget.19382.].

High Difference-Frequency Generation in SiO2/MnF2/Ag Sandwich Structures.

In this work, a simple antiferromagnetic (AF) sandwich structure is proposed to increase the difference-frequency (DF) outputs, where a noble metal, Ag layer, is put under an AF film. Numerical calculations are based on the SiO2/MnF2/Ag sandwich structure, where MnF2 is a typical AF material. We found that the DF outputs on the above surface are increased at least two orders which compared with those of MnF2 film. The continuous DF windows show that the outputs decrease with the increasing incident angles. The effect of the external magnetic field on DF outputs is also discussed.

Generation of Elliptically Polarized Terahertz Waves from Antiferromagnetic Sandwiched Structure.

The generation of elliptically polarized electromagnetic wave of an antiferromagnetic (AF)/dielectric sandwiched structure in the terahertz range is studied. The frequency and external magnetic field can change the AF optical response, resulting in the generation of elliptical polarization. An especially useful geometry with high levels of the generation of elliptical polarization is found in the case where an incident electromagnetic wave perpendicularly illuminates the sandwiched structure, the AF anisotropy axis is vertical to the wave-vector and the external magnetic field is pointed along the wave-vector. In numerical calculations, the AF layer is FeF2 and the dielectric layers are ZnF2. Although the effect originates from the AF layer, it can be also influenced by the sandwiched structure. We found that the ZnF2/FeF2/ZnF2 structure possesses optimal rotation of the principal axis and ellipticity, which can reach up to about thrice that of a single FeF2 layer.

Aliskiren therapy in hypertension and cardiovascular disease: a systematic review and a meta-analysis.

The efficacy and safety of aliskiren combination therapy with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in patients with hypertension and cardiovascular disease remains attractive attention. We searched the Cochrane Central Register, the Clinical Trials Registry, EMBASE, MEDLINE and PubMed for relevant literatures up to January 2017. A total of 13 randomized controlled trials (RCTs) with 12222 patients were included in this study, and the combined results indicated that aliskiren in combination therapy with ACEIs or ARBs had remarkable effects in reducing systolic blood pressure (SBP) [weighted mean differences (WMD), -4.20; 95% confidential intervals (CI) -5.44 to -2.97; I2 , 29.7%] and diastolic blood pressure (DBP: WMD, -2.09; 95% CI -2.90 to -1.27; I2 , 0%) when compared with ACEIs or ARBs monotherapy, but with significantly increased the risk of hyperkalaemia [relative risk (RR), 1.45; 95% CI 1.28 to 1.64; I2 ,10.6 %] and kidney injury ( RR, 1.92; 95% CI 1.14 to 3.21; I2 , 0%). Besides, there was no significant difference in the incidence of major cardiovascular events (RR, 0.95; 95% CI 0.89 to 1.02; I2 , 0%) between the combined therapy and ACEIs or ARBs monotherapy. In conclusion, this meta-analysis demonstrated that aliskiren in combination therapy with ACEs/ARBs could control BP effectively, but is associated with increasing risks of hyperkalaemia and kidney injury, and have no benefit in preventing of major cardiovascular events.