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Natural killer (NK) cells eliminate infected or cancer cells via their cytotoxic capacity. NKG2A is an inhibitory receptor on NK cells and cancer cells often overexpress its ligand HLA-E to evade NK cell surveillance. Given the successes of immune checkpoint blockade in cancer therapy, NKG2A is an interesting novel target. However, anti-NKG2A antibodies have shown limited clinical response. In the pursuit of enhancing NK cell-mediated anti-tumor responses, we devised a Cas9-based strategy to delete KLRC1, encoding NKG2A, in human primary NK cells. Our approach involved electroporation of KLRC1-targeting Cas9 ribonucleoprotein resulting in effective ablation of NKG2A expression. Compared with anti-NKG2A antibody blockade, NKG2AKO NK cells exhibited enhanced activation, reduced suppressive signaling, and elevated expression of key transcription factors. NKG2AKO NK cells overcame inhibition from HLA-E, significantly boosting NK cell activity against solid and hematologic cancer cells. We validated this efficacy across multiple cell lines, a xenograft mouse model, and primary human leukemic cells. Combining NKG2A knockout with antibody coating of tumor cells further enhanced cytotoxicity through ADCC. Thus, we provide a comprehensive comparison of inhibition of the NKG2A pathway using genetic ablation and antibodies and provide novel insight in the observed differences in molecular mechanisms, which can be translated to enhance adoptive NK cell immunotherapy.
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Células Matadoras Naturais , Subfamília C de Receptores Semelhantes a Lectina de Células NK , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Subfamília C de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília C de Receptores Semelhantes a Lectina de Células NK/metabolismo , Animais , Camundongos , Linhagem Celular Tumoral , Antígenos HLA-E , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/genética , Anticorpos Monoclonais/farmacologia , Sistemas CRISPR-Cas , Deleção de Genes , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/metabolismo , Citotoxicidade ImunológicaRESUMO
The multi-channel perfect vortex (PV) array based on metasurface has important applications in optical communication, particle manipulation, quantum optics, and other fields due to its ultra-thin structure and excellent wavefront control ability. However, it is very challenging to utilize a single metasurface to simultaneously achieve independent channel PV arrays at different wavelengths with low crosstalk and low structural complexity. Here, we propose and design a single rectangular structured metasurface based on TiO2, achieving a multi-channel PV beam array with dual-wavelength and dual-polarization multiplexing. Simulation and experimental results show that when two orthogonal linearly polarized beams with wavelengths of 532 nm and 633 nm are incident on the metasurface, clear PV arrays with corresponding topological charge arrangements can be obtained in different diffraction regions of the same observation plane. The metasurface proposed in this article can enhance the channel capacity of a PV beam array through wavelength-polarization-multiplexing, thus having important application potential in spatial information transmission, high-dimensional information storage, and secure information encryption.
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Non-Abelian holonomy, a noncommutative process that measures the parallel transport of non-Abelian gauge fields, has so far been realized in degenerate Hermitian systems with degenerate eigenstates or nondegenerate non-Hermitian systems with exceptional points. Here, we introduce non-Abelian holonomy into degenerate non-Hermitian systems possessing degenerate exceptional points and degenerate energy topologies. The interplay between energy degeneracy and energy topology around exceptional points leads to a non-Abelian holonomy with multiple energy levels and multiple degenerate levels simultaneously, going beyond that in degenerate Hermitian systems with a single energy level, or in nondegenerate non-Hermitian systems with a single degenerate level. We exploit an on-chip photonic platform to experimentally demonstrate the holonomy induced non-Abelian phenomenon, including the switching of eigenstates associated with different degenerate exceptional points and sequence-dependent holonomic outcomes. Our work shifts the paradigm of non-Abelian holonomy and adds new degrees of freedom for non-Abelian applications.
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BACKGROUND: Preventing emergence delirium is a clinical goal for pediatric anesthesia, yet there is no consensus on its prevention. This study investigated the hypothesis that a continuous infusion or a single bolus of remimazolam can reduce the incidence of emergence delirium in children. METHODS: A total of 120 children aged 1 to 6 yr were randomly and equally allocated into three groups: group RC, which received a continuous infusion of remimazolam at 1 mg · kg-1 · h-1; group RB, which received a single bolus of remimazolam at 0.2 mg · kg-1 at the beginning of wound closure; and group C, which received a continuous infusion of saline at 1 ml · kg-1 · h-1 and a single bolus of saline at 0.2 ml · kg-1 at the beginning of sutures. The primary outcome was the incidence of emergence delirium assessed by the Pediatric Anesthesia Emergence Delirium scale. Secondary outcomes included the number of rescue propofol administrations in the postanesthesia care unit, recovery time, and adverse events. RESULTS: Emergence delirium was observed in 14 of 40 (35%) patients in group C, 2 of 40 (5%) patients in group RC (vs. group C, P = 0.001; risk ratio, 95% CI: 0.14, 0.04 to 0.59), and 3 of 39 (7.7%) patients in group RB (vs. group C, P = 0.003; risk ratio, 95% CI: 0.22, 0.07 to 0.71). Ten of 40 patients in group C, 2 of 40 patients in group RC (vs. group C, P = 0.012; risk ratio, 95% CI: 0.20, 0.05 to 0.86), and 2 of 39 patients in group RB (vs. group C, P = 0.014; risk ratio, 95% CI: 0.21, 0.05 to 0.88) needed rescue propofol. No differences in the recovery time and adverse effects were detected. CONCLUSIONS: Both continuous infusion and single bolus administration of remimazolam can effectively reduce the occurrence of emergence delirium in children.
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Benzodiazepinas , Delírio do Despertar , Hipnóticos e Sedativos , Laparoscopia , Humanos , Delírio do Despertar/prevenção & controle , Delírio do Despertar/epidemiologia , Masculino , Feminino , Pré-Escolar , Método Duplo-Cego , Lactente , Criança , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Benzodiazepinas/uso terapêutico , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/uso terapêutico , Período de Recuperação da Anestesia , Infusões IntravenosasRESUMO
In this work, a simple dielectric metasurface hologram is proposed and designed by combining the electromagnetic vector analysis method and the immune algorithm, which can realize the holographic display of dual wavelength orthogonal-linear polarization light in visible light band, solve the problem of low efficiency of the traditional design method of metasurface hologram, and effectively improve the diffraction efficiency of metasurface hologram. The titanium dioxide metasurface nanorod based on rectangular structure is optimized and designed. When the x-linear polarized light with wavelength of 532â nm and y-linear polarized light with wavelength of 633â nm are incident on the metasurface respectively, different display output images with low cross-talk can be obtained on the same observation plane, and the transmission efficiencies of x-linear and y-linear polarized light are as high as 68.2% and 74.6% respectively in simulation. Then the metasurface is fabricated by Atomic Layer Deposition method. The experimental results are consistent with the design results, which proves that the metasurface hologram designed by this method can completely realize the feasibility of wavelength and polarization multiplexing holographic display, and has potential application value in holographic display, optical encryption, anti-counterfeiting, data storage and other fields.
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The metalens has vast applications in biomedicine and industrial manufacturing due to their ultrathin structure and vital ability to manipulate the properties of light waves for long-infrared systems. However, it is difficult for metalens to achieve the confocal function with high focusing efficiency, wide wavelength bandwidth, and low structural complexity. Here, we propose and experimentally demonstrate an all-silicon dielectric metalens composed of arrays of minimalist meta-atoms with a single rectangular nanopillar arranged on a periodic square lattice substrate, which realizes the confocal function of the orthogonal-linear-polarized light with wavelengths of 10.6â µm and 9.3â µm, with focusing efficiencies of 64.94% and 60.03%, respectively. Also, it reveals nearly the diffraction-limited focusing performance. In addition, the metalens can realize precise long-infrared thermal imaging. Moreover, the proposed metalens is compatible with the standard complementary metal oxide semiconductor processes, which can effectively reduce the manufacturing cost and provide a feasible solution for developing planar integrated multifunctional micro-nanophotonic devices in the long-infrared field.
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The implementation of transverse mode, polarization, frequency, and other degrees of freedom (d.o.f.s) of photons is an important way to improve the capability of photonic circuits. Here, a three-dimensional (3D) linear polarized (LP) LP11 mode converter was designed and fabricated using a femtosecond laser direct writing (FsLDW) technique. The converter included multi-mode waveguides, symmetric Y splitters, and phase delaying waveguides, which were constructed as different numbers and arrangements of circular cross section waveguides. Finally, the modes (LP11a and LP11b) were generated on-chip with a relatively low insertion loss (IL). The mode converter lays a foundation for on-chip high-order mode generation and conversion between different modes, and will play a significant role in mode coding and decoding of 3D photonic circuits.
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Removing phosphate from wastewater can help alleviate eutrophication. Therefore, in this study, lanthanum and magnesium were loaded onto the thermally modified palygorskite (PAL) using a coprecipitation method, and a composite material was prepared for phosphate recovery. In the pH range of 2-7, the material can effectively adsorb the phosphate. In the kinetic experiment, the material was able to rapidly adsorb phosphate within 4 h of the beginning of the reaction. The adsorption isotherm result of the material was in accordance with Freundlich isotherm model. When pH was 7, the theoretical maximum adsorption capacity was 20.4 mg P/g. When phosphate coexisted with CO32- and HCO3-, the adsorption was significantly inhibited. In the adsorption-desorption experiment, the material can be reused at least five times after elution with 1 mol/L of sodium hydroxide solution. The equilibrium adsorption capacity of the material for total phosphorus in piggery wastewater was 7.25 mg P/g, achieving a total phosphorus removal rate of 95.3%. The characterization of XRD, FT-IR and XPS suggested that phosphate was mainly exchanged with La-OH in the material, forming an amorphous LaPO4 complex.
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Posterior capsule opacification (PCO), resulting from residual lens epithelial cell (LEC) epithelial-mesenchymal transition (EMT), abnormal proliferation, and migration, is the most common complication of cataract surgery. A recent study determined that extracellular vesicles (EVs) and reactive oxygen species (ROS) regulate the EMT process during cutaneous wound healing and tumour metastasis. However, their underlying mechanism in PCO is unclear. In this study, we examined the secreted EVs from a scratch model in vitro. We found that the production of ROS was increased after mechanical injury, especially at the wound edge, and there was an increased viability of LECs, which can be blocked by diphenyleneiodonium, an NADPH oxidase inhibitor. Cell viability and migration were increased upon treatment with 1 µM H2O2, but significantly reduced when the concentration of H2O2 increased to 100 µM. Transwell assay showed that both post-surgery LECs and LECs treated with 1 µM H2O2 significantly induced the migration of normal LECs by EV secretion. Extraction and quantification of EVs derived from injured and H2O2-treated LECs showed a similar increase in production. Co-incubation of EVs from both injured and H2O2-treated LECs with normal LECs and organ-cultured mouse lenses activated EMT, which was attenuated by a ROS inhibitor. These results suggest that EVs participate in ROS-induced lens EMT, making EVs a potential target for treating PCO.
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Células Epiteliais/metabolismo , Vesículas Extracelulares/metabolismo , Cristalino/metabolismo , Células Cultivadas , Células Epiteliais/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Vesículas Extracelulares/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/farmacologia , Cristalino/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacosRESUMO
BACKGROUND: The anterolateral thigh flap is one of the most widely used flaps because it has the advantages of less damage to the donor site, no sacrifice of main blood vessels, and abundant soft tissue. However, the application of anterolateral thigh flap in children is relatively rare because of small blood vessels and rapid physiological changes. The aim of this study was to explore the effectiveness and characteristics of free anterolateral thigh flaps for the reconstruction of extremity soft tissue defects in pediatric patients. PATIENTS AND METHODS: This study included 26 pediatric patients, with an average age of 6.7 years (range, 2-13 years). There were 5 cases of upper limb defects and 21 cases of lower limb defects, all of which were accompanied by exposed bones or tendons. The causes of defects included traffic injury in 9 cases, mechanical injury in 7 cases, collision injury in 4 cases, spoke injury in 3 cases, cicatricial contracture in 2 cases, and fibroma in 1 case. All defects were reconstructed with free anterolateral thigh flaps. RESULTS: Twenty-six anterolateral thigh flaps were harvested, including 15 fasciocutaneous flaps and 11 musculocutaneous flaps. The mean size of the flap was 73.4 cm 2 (range, 4 × 3 to 24 × 8 cm). The donor sites were sutured directly in 19 cases and underwent split-thickness skin grafting in 7 cases. There were 3 cases of vascular crisis, 3 cases of flap edge necrosis, 3 cases of infection, 1 case of pressure ulcer, and 1 case of dehiscence after surgery. Eleven patients had scar hyperplasia in the donor site. A total of 34 reoperations were performed, including 14 flap debulking, 7 debridement, 4 skin graft, 3 vascular crisis re-exploration, and 6 other procedures. CONCLUSIONS: Free anterolateral thigh flap was a safe and reliable option for reconstructing soft tissue defects of extremities in pediatric patients. Notably, the incidence of scar hyperplasia in the donor site and the possibility of reoperation in pediatric patients were higher than those in adult patients.
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Retalhos de Tecido Biológico , Retalho Perfurante , Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Adulto , Criança , Cicatriz/cirurgia , Humanos , Hiperplasia , Retalho Perfurante/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Transplante de Pele , Lesões dos Tecidos Moles/cirurgia , Coxa da Perna/cirurgia , Resultado do TratamentoRESUMO
An extremely sensitive multi-order mode refractive index (RI) sensor was fabricated by coupling titanium dioxide nanograss film coated FTO conductive glass with Kretschmann prism. Both calculation and experimental studies were carried out. Theoretical analysis by employing resonant waveguide modes indicated that the maximum sensitivity could be achieved when the mode worked at the weakly-bounded condition. The experimental results showed that for p-polarized and s-polarized light, the sensor exhibited a maximum RI sensitivity of 2938.21 nm/RI unit (RIU) and 1484.39 nm/RIU in the 1st order mode, respectively. Its maximum figure of merit was as high as 77.77. The proposed sensor is promising to be applied in environmental monitoring, immune analysis, nucleic acid test, etc.
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We report an omnidirectional light absorption enhancement of a perovskite solar cell (PSC) using antireflection (AR) film with soft imprinted microstructures from master molds via holographic lithography technology, which has high throughput and repeatability. The PSC's omnidirectional power conversion efficiency (PCE) enhancement is achieved by reducing Fresnel surface reflections and enhancing the optical path length. The maximum PCE of PSCs with AR film is up to 20.27%, corresponding to an absolute increase of 0.93% compared to 19.34% of control devices. Significantly, the enhancements of PCE increase with incident angle enlargement, which attributes to more effective Fresnel surface reflection suppression. Moreover, AR films exhibit water and dust repellent properties due to hydrophobicity, which is beneficial for PSC's long-term stability and light harvesting.
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Dynamically encircling an exceptional point in non-Hermitian systems has drawn great attention recently, since a nonadiabatic transition process can occur and lead to intriguing phenomena and applications such as the asymmetric switching of modes. While all previous experiments have been restricted to two-state systems, the dynamics in multistate systems where more complex topology can be formed by exceptional points, is still unknown and associated experiments remain elusive. Here, we propose an on-chip photonic system in which an arbitrary number of exceptional points can be encircled dynamically. We reveal in experiment a robust state-switching rule for multistate systems, and extend it to an infinite-period system in which an exceptional line is encircled with outcomes being located at the Brillouin-zone boundary. The proposed versatile platform is expected to reveal more physics related to multiple exceptional points and exceptional lines, and give rise to applications in multistate non-Hermitian systems.
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The introduction of non-Hermiticity into photonics has enabled new design principles for photonic devices. Here we propose the design of a tunable non-Hermitian on-chip mode converter working at telecommunication wavelengths. The key component of the converter is a phase change material, and switching its working state can enable a topological change in the energy surface of the system. The conversion functionality can be realized by dynamically encircling an exceptional point in the parameter space of the device. The device based on this non-Hermitian principle is robust to perturbations of structural parameters and works in broadband. The non-Hermitian principle can be applied for the design of more complex on-chip photonic devices.
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We report an improved light extraction in all-inorganic perovskite light-emitting devices (PeLEDs) by integrating a periodic corrugated nanostructure at the metallic cathode/organic interface. Nanoimprinting lithography was used to introduce the nanostructures onto the surface of the electron transport layer directly to avoid influencing the morphology and crystallinity of the perovskite film underneath. The trapped energy at the metallic electrode has been successfully outcoupled by the excitation of the surface plasma polariton (SPP) modes induced by the periodic corrugations. The luminance and current efficiency of the periodically corrugated PeLED exhibit enhancements of 42% and 28%, respectively, compared to those of the planar PeLED. The finite-difference time-domain simulation was used to confirm the efficient outcoupling of the SPP modes.
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An ultrathin metal film with high transmittance and conductivity has been demonstrated to be a promising transparent electrode for organic light-emitting devices (OLEDs). However, mediocre surface morphology and continuity of evaporated metal films and the surface plasmon-polaritons (SPPs) energy loss between the metal electrode and organic layer still limit the external quantum efficiency (EQE) of OLEDs. Here, nanoimprint lithography has been directly applied on the ultrathin Au film with underlying uncured photopolymer to fabricate the nanopillared anode. Both the conductivity and transmittance of the nanopillared ultrathin Au film have been improved due to the improvement of continuity and surface smoothness. As we expected, the SPPs mode has been coupled into photons and further extracted from OLEDs by using the nanopillared Au film anode. Finally, 19.2% and 70.1% enhancement of current efficiency were achieved compared to the planar device with ultrathin Au anode and ITO anode, respectively.
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Dynamically encircling exceptional points (EPs) can lead to chiral mode switching as the system parameters are varied along a path that encircles EP. However, conventional encircling protocols result in low transmittance due to path-dependent losses. Here, we present a paradigm to encircle EPs that includes fast Hamiltonian variations on the parameter boundaries, termed Hamiltonian hopping, enabling ultrahigh-efficiency chiral mode switching. This protocol avoids path-dependent loss and allows us to experimentally demonstrate nearly 90% efficiency at 1550 nm in the clockwise direction, overcoming a long-standing challenge of non-Hermitian optical systems and powering up new opportunities for EP physics.
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We demonstrate an enhanced efficiency of all-inorganic perovskite light-emitting diodes (PeLEDs) by doping an electron acceptor of 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4-TCNQ) as a p-type dopant into the hole-transport layer (HTL) of poly-triarylamine (PTAA). The conductivity of the PTAA was improved by the formation of the CT complex through the electron transfer from the PTAA to F4TCNQ. Moreover, the hydrophobic surface of the PTAA leads to an improved surface morphology of the perovskite films compared to that on the conventionally used HTL of PEDOT:PSS. As a result, the maximum luminance and efficiency for the doped PTAA-based PeLEDs are 28020 cd/m2 and 13.5 cd/A, respectively, corresponding to 32.7% and 48% improvement in the efficiency compared to those of the pure PTAA or PEDOT:PSS-based PeLEDs.
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In our lab, the coefficient relational expressions called A(L,H), B(L,H), and C(L,H) between the coefficients in the microprism distribution expression and the structural parameters of the integrated light guide plate, which is to realize high luminance uniformity, have been proposed previously. Yet, there are some deficiencies in these coefficient relational expressions, such as numerical item redundancy and inconspicuous physical characterization. On this basis, the revised coefficient relational expressions of A(L,H), B(L,H), and C(L,H) are further studied. As a result, the numerical items of A(L,H), B(L,H), and C(L,H) are reduced by one-quarter, one-third, and one-half, respectively. The redundant high-order items are reduced, and C(L,H) is no longer a piecewise function. After revision, the effect of each numerical item on the coefficient values is highlighted, and it makes the physical characterization of each numerical term clearer. Moreover, by applying the revised coefficient relational expressions to acquire the microprism distribution, the luminance uniformities of all designed integrated backlight modules of 7.0 in. or less in size are totally higher than 85%. Taking a 5.0 in. integrated backlight module as an example, the performance of the integrated backlight module designed by the revised coefficient relational expressions is also improved over that before the revision. It verifies the correctness, effectiveness, and universality of the revised coefficient relational expressions, which will save a lot of design time.
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The response of a novel long-period fiber grating (LPFG) with a period of 180 µm to a surrounding refractive index (RI) was investigated. The results displayed that, with the increase in RI of the surrounding media of cladding glass in the grating region, the resonant peak located at 1336.4 nm in the transmission spectrum gradually shifts towards a shorter wavelength, while the resonant peak located at 1618 nm gradually shifted towards a longer wavelength. Moreover, the resonant peak at 1618 nm is much more sensitive to the surrounding RI than that of the one at 1336.4 nm. Compared with the conventional LPFG and other types of wavelength-interrogated RI sensors, such as ring resonators, surface plasmon resonance sensors, and Fabry-Perot interferometric sensors, this novel LPFG possesses a higher sensitivity, which achieved 10,792.45 nm/RIU (RI unit) over a RI range of 1.4436-1.4489.