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INTRODUCTION: A hypersensitivity response akin to immune reconstitution inflammatory syndrome (IRIS) has been proposed as a mechanism responsible for anti-PD-1 therapy-induced tuberculosis. IRIS is associated with enhanced activation of IL-17A-expressing CD4 + T cells (Th17). Gut microbiota is thought to be linked to pulmonary inflammation through the gut-lung axis. MATERIALS AND METHODS: We used ImmuCellAI to investigate the T cell population in lung cancer and tuberculosis samples. Then, we applied flow cytometry to monitor the expression levels of the Th17 cell activation marker CD38 in the peripheral blood of a patient experiencing adverse events, including tuberculosis, in response to pembrolizumab. The gut microbiome was examined by 16S rRNA sequencing to examine the alterations caused by pembrolizumab. RESULTS: The percentage of Th17 cells was increased in both lung cancer and tuberculosis. FACS analysis showed that pembrolizumab induced substantial CD38 expression in Th17 cells. The patient's fecal samples showed that the diversity of the gut microbiota was significantly increased in response to the pembrolizumab cycle. One enriched genus was Prevotella, which has previously been linked to lung inflammation and Th17 immune activation. DISCUSSION: The observed Th17 activation in our patient was consistent with a role of Th17-mediated IRIS in pembrolizumab-triggered tuberculosis. Pembrolizumab might trigger airway inflammation with a Th17 phenotype through microbiota interactions in the gut-lung axis.
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Anticorpos Monoclonais Humanizados/efeitos adversos , Microbioma Gastrointestinal/imunologia , Síndrome Inflamatória da Reconstituição Imune/imunologia , Neoplasias Pulmonares/tratamento farmacológico , Células Th17/imunologia , Tuberculose/imunologia , Antituberculosos/uso terapêutico , DNA Bacteriano/isolamento & purificação , Conjuntos de Dados como Assunto , Microbioma Gastrointestinal/genética , Humanos , Síndrome Inflamatória da Reconstituição Imune/sangue , Síndrome Inflamatória da Reconstituição Imune/induzido quimicamente , Síndrome Inflamatória da Reconstituição Imune/microbiologia , Pulmão/diagnóstico por imagem , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/microbiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/isolamento & purificação , Prevotella/genética , Prevotella/imunologia , Prevotella/isolamento & purificação , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , RNA Ribossômico 16S/genética , Células Th17/efeitos dos fármacos , Tomografia Computadorizada por Raios X , Tuberculose/induzido quimicamente , Tuberculose/tratamento farmacológico , Tuberculose/microbiologiaRESUMO
Thermal conductivity is an important physical parameter for the application of nonlinear optical single crystal materials. The underlying science of thermal transport behavior is not well established both experimentally and theoretically. In the present work, we have studied the microscopic picture of lattice thermal conductivity of ZnXP2 (X = Si, Ge, Sn), chalcopyrite ABC2 type infrared optical crystals, by using a harmonic and anharmonic lattice dynamic method and phonon Boltzmann transport equation based on first-principle calculations. With the mass of atom X increased, the phonon frequencies and phonon group velocities of ZnXP2 (X = Si, Ge, Sn) are shown not surprisingly to be decreased. Nevertheless, the phonon lifetime of ZnXP2 is unexpectedly increased, which is the governing mechanism for the increased thermal conductivity as 12.5 W/(m·k), 31.6 W/(m·k), and 35.4 W/(m·k), for ZnSiP2, ZnGeP2, and ZnSnP2, respectively, at 300 K. The contributions of optical phonons (with the frequency below 150 cm-1) to the total thermal conductivity are remarkable, reaching 18%, 31%, and 34% for three compounds, due to the significantly increased phonon lifetime in the frequency range 50-150 cm-1. To explore the physical insights of phonon lifetime and phonon anharmonicity, three-phonon scattering phase space and electronic localization function analysis of the X-P bond are provided. The results show that the covalent nature of X-P bonds is enhanced with the increased mass of atom X = Si, Ge, Sn, which induces the reduction of three-phonon scattering phase space in the frequency range 50-150 cm-1, leading to the enhancement of the phonon lifetime and thermal conductivity of ZnXP2.
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The plate-like iron-rich intermetallic phases in recycled aluminum alloys significantly deteriorate the mechanical properties. In this paper, the effects of mechanical vibration on the microstructure and properties of the Al-7Si-3Fe alloy were systematically investigated. Simultaneously, the modification mechanism of the iron-rich phase was also discussed. The results indicated that the mechanical vibration was effective in refining the α-Al phase and modifying the iron-rich phase during solidification. The forcing convection and a high heat transfer inside the melt to the mold interface caused by mechanical vibration inhibited the quasi-peritectic reaction: L + α-Al8Fe2Si â (Al) + ß-Al5FeSi and eutectic reaction: L â (Al) + ß-Al5FeSi + Si. Thus, the plate-like ß-Al5FeSi phases in traditional gravity-casting were replaced by the polygonal bulk-like α-Al8Fe2Si. As a result, the ultimate tensile strength and elongation were increased to 220 MPa and 2.6%, respectively.
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Research on rare-earth fluorides is of urgent and critical importance for the preparation and emerging applications of high-purity alloys. The fluorination of Sc2O3 by NH4HF2 to fabricate ScF3 is investigated. The effects of the fluorination temperature, time and mass ratio of reactant on the fluorination rate and fluoride are discussed in this work. The fluorination reaction was first confirmed using thermodynamic calculation. The thermal and mass stability of the fluorination process were analyzed by thermogravimetric and differential scanning calorimetric (TG-DSC). The as-obtained products at different fluorination temperatures were characterized by Powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (HRTEM). The results indicated that the fluorination began at room temperature (RT) with the formation of (NH4)3ScF6. With the increase of temperature, the reaction proceeded sequentially through the formation of NH4ScF4, (NH4)2Sc3F11, and finally ScF3. The fluorination rate increased with the increase of fluorination temperature and holding time. ScF3 with a purity of 99.997 wt.% could be obtained by fluorination at 400 °C for 2 h.
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The involvement of magnesium matrix composite enhanced by metal particles, the development of low lattice mismatch interface, and the refining of particle size are all of great significance in improving strengthening efficiency. In this work, nano-crystalline Ti/Mg-9Al-Zn-0.3Mn composites were prepared by mechanical milling. The microstructure was characterized and the mechanical property was measured. After mechanical milling, the grain of the Mg matrix was refined to ~72 nm. Ti particles were smashed to submicron scale, and dispersed in the Mg matrix. In total, 68% of Ti particles were nano-scale and the average particle size was 133 nm. A nano-scale Mg17Al12 precipitate was found and the average particle size was approximately 44 nm. Meanwhile, coherent interfaces of Ti/Mg and Mg17Al12/Mg were observed, and it was found that the (101)Mg plane and (100)Ti plane inclined 12° and [044]Mg17Al12 was parallel to [010]Mg. The hardness of the milled Ti/Mg-9Al-Zn-0.3Mn composite was 1.98 GPa, 247% higher than the initial alloy. Milled Mg-9Al-Zn-0.3Mn alloy under the same preparation processing was used as a comparison, and the value of hardness was 1.53 GPa. Tiny Ti particles displayed excellent strengthening efficiency. Strengthening mechanisms of the milled Ti/Mg-9Al-Zn-0.3Mn composite were analyzed and the main strengthening mechanisms included the strengthening of grain boundary strengthening, Orowan strengthening, dislocation strengthening, solid solution strengthening and load-bearing strengthening, which accounted for 56.3%, 18.2%, 17.4%, 4.7% and 3.5%, respectively.
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Since the commercial applications of rare earth magnesium alloys are increasing gradually, there are considerable advantages to developing lower cost and higher performance magnesium alloys with high abundance rare earth (RE) elements. However, the alloying order of a matrix magnesium alloy is completely changed with the addition of RE elements. Therefore, further study of the strengthening mechanism of Ce element in magnesium alloys is required. In this work, the thermodynamic stability of the possible second phases in a Mg-Al-Mn-Ce multicomponent magnesium alloy were analyzed, based on first-principle calculations, and the precipitation sequence of the key RE phases was deduced as a consequence. Combined with Scanning Electron Microscope (SEM), X-ray Diffractometer (XRD), Energy Dispersive Spectrometer (EDS), and other experimental methods, it was investigated whether the preferentially precipitated second phases were the nucleation core of primary α-Mg. The complex alloying problem and strengthening mechanism in a multi-elemental magnesium alloy system were simplified with the aid of electronegativity theory. The results showed that the preferentially precipitated Al11Ce3 and Al10Ce2Mn7 phases could not be the nucleation core of primary α-Mg, and the grain refinement mechanism was such that the second phases at the grain boundary prevented the growth of magnesium grains. Moreover, the tensile test results showed that the reinforced structure, in which the Al-Ce phase was mixed with Mg-Al phase, was beneficial for improving the mechanical properties of magnesium alloys, at both ambient temperature and high temperature.
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The appearance of the ε phase during the welding process can severely weaken the welding strength of dissimilar metals of Mg-Zn-Al alloy systems. An understanding of the accurate phase diagram, especially the equilibrium phase relation around the ε phase, is thus of particular importance. However, the phase interrelation near the ε-Mg23(Al, Zn)30 phase has not yet been fully studied. In this work, the local phase diagrams of the ε phase and its surrounding phases in the Mg-Zn-Al system are systematically determined by experimental investigation and thermodynamic verification. Five Mg-Zn-Al alloys and one diffusion couple were fabricated and analyzed to get accurate phase constituents and relationships adjacent to ε phase. The current experimental data obtained from Scanning Electron Microscope (SEM), X-ray diffraction (XRD), Differential Scanning Calorimetry (DSC), and Electron Probe Micro Analysis (EPMA) were further compared with the thermodynamically computed phase relations around ε phase for verification, showing good agreements. Several important conclusions are drawn based on current experimental work, which can provide supporting information for the follow-up studies on ε phase in the Mg-Zn-Al alloy systems.
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The development of a magnesium matrix composite with a high content of dispersions using conventional liquid-phase process is a great challenge, especially for nanometer/submicron particles. In this work, mechanical milling was employed to prepare nanocrystalline AZ91 dispersed with 15 vol.% submicron SiC particles (SiCp/AZ91). AZ91 with no SiCp was applied as a comparative study with the same mechanical milling. In order to investigate the mechanism of dispersing, the morphology evolution of powders and the corresponding SiCp distribution were observed. As the scanning electron microscope (SEM) analysis exhibited, the addition of SiCp accelerated the smashing of AZ91 particles, which promoted the dispersion of SiCp in AZ91. Thus, after mechanical milling, 15 vol.% SiCp, which was smashed from 800 to 255 nm, got uniformly distributed in the Mg matrix. Based on X-ray diffraction (XRD) results, part of the Mg17Al12 precipitate got dissolved, and an Al-supersaturated Mg solid solution was formed. The transmission electron microscopy (TEM) results showed that the ultimate Mg grain (32 nm) of milled SiCp/AZ91 was much smaller than that of milled AZ91 (64 nm), which can be attributed to a pinning effect of submicron SiCp. After mechanical milling, the hardness of SiCp/AZ91 reached 185 HV, which was 185% higher than the original AZ91 and 33% higher than milled AZ91, due to fine Mg grain and submicron dispersions.
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In this paper, a new type of low-cost Mg-3.36Zn-1.06Sn-0.33Mn-0.27Ca (wt %) alloy ingot with a diameter of 130 mm and a length of 4800 mm was fabricated by semicontinuous casting. The microstructure and mechanical properties at different areas of the ingot were investigated. The microstructure and mechanical properties of the alloy under different one-step and two-step homogenization conditions were studied. For the as-cast alloy, the average grain size and the second phase size decrease from the center to the surface of the ingot, while the area fraction of the second phase increases gradually. At one-half of the radius of the ingot, the alloy presents the optimum comprehensive mechanical properties along the axial direction, which is attributed to the combined effect of relatively small grain size, low second-phase fraction, and uniform microstructure. For the as-homogenized alloy, the optimum two-step homogenization process parameters were determined as 340 °C × 10 h + 520 °C × 16 h. After the optimum homogenization, the proper size and morphology of CaMgSn phase are conducive to improve the microstructure uniformity and the mechanical properties of the alloy. Besides, the yield strength of the alloy is reduced by 20.7% and the elongation is increased by 56.3%, which is more favorable for the subsequent hot deformation processing.
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Electrical connection of dissimilar metals will lead to galvanic corrosion. Therefore, overall surface treatment is necessary for the protection of dissimilar metal welded parts. However, serious unbalanced reactions may occur during overall surface treatment, which makes it difficult to prepare integral coating. In this paper, an overall ceramic coating was fabricated by plasma electrolytic oxidation to wrap the 6061-7075 welded part integrally. Moreover, the growth mechanism of the coating on different areas of the welded part was studied based on the dielectric breakdown theory. The reaction sequence of each area during the treatment was verified through specially designed dielectric breakdown tests. The results showed that the high impedance overall of ceramic coating can inhibit the galvanic corrosion of the 6061-7075 welded part effectively.
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The construction, characterization and surgical application of a multilayered iron oxide-based macroporous composite framework were reported in this study. The framework consisted of a highly porous iron oxide core, a gelatin-based hydrogel intermediary layer and a matrigel outer cover, which conferred a multitude of desirable properties including excellent biocompatibility, improved mechanical strength and controlled biodegradability. The large pore sizes and high extent of pore interconnectivity of the framework stimulated robust neovascularization and resulted in substantially better cell viability and proliferation as a result of improved transport efficiency for oxygen and nutrients. In addition, rat models with myocardial infraction showed sustained heart tissue regeneration over the infract region and significant improvement of cardiac functions following the surgical implantation of the framework. These results demonstrated that the current framework might hold great potential for cardiac repair in patients with myocardial infraction.