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Consolidating nanopowder metals via impact loading is a potentially significant method for synthesizing and processing bulk nanocrystalline materials. However, until now, the microstructural features, plastic deformation during consolidation, and corresponding mechanisms have been seldom revealed. Using molecular dynamics (MD) simulations, we have studied the plastic deformation, densification, spallation, and micro-jetting in nanopowder titanium (np-Ti) during shock. Upon impact, np-Ti undergoes a transition from heterogeneous plasticity, including basal stacking faults (SFs) and {101Ì2} twinning, to homogeneous disordering, as the impact velocity increases. Then the nanopowder structure evolves into a bulk nanostructure after the final densification, contributed by pore collapse. The subsequent detwinning arises during the release and tension stage, conducing to a partial structural recovery. When the impact velocity up ≥ 1.0 km s-1, the spallation is following, prompted via GB-sliding and disordering. Upon shock impact, it also facilitates micro-jetting owing to the presence of nanopores, contributing to the pressure gradient and transverse velocity gradient.
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BACKGROUND: Cancer immunotherapies can induce durable tumor regression, but most patients do not respond. SETD2 mutation has been linked to the efficacy of immune checkpoint inhibitors (ICIs) immunotherapy. The functional importance of the SETD2 inactivation and how to modulate immunotherapy response remains unclear. METHODS: To explore the function of SETD2 in immunotherapy, knockout and subsequent functional experiments were conducted. Bulk RNA-seq, ATAC-seq, Chip-seq and single-cell RNA-seq were performed to dissect the mechanism and explore the immune microenvironment of mouse tumor. Flow cytometry was used to assess cell surface antigen and intratumoral T cell levels. RESULTS: We comprehensively determine the effect of SETD2 inactivation in ICIs therapy and elucidate the mechanistic impact on tumor immunity. Murine syngeneic tumors harboring Setd2 inactivation are sensitive to ICIs. By bulk and single-cell RNA-seq, we further reveal that SETD2 inactivation reprograms intratumoral immune cells and inflames the tumor microenvironment, which is characterized by high infiltration of T cells and enhanced antigen presentation to activate CD8+ T cell-mediated killing. Mechanistically, via an integrated multiomics analysis using ATAC-seq, ChIP-seq and RNA-seq, we demonstrate that SETD2 inactivation reduces NR2F1 transcription by impairing H3K36me3 deposition and chromatin accessibility, which activates the STAT1 signaling pathway to promote chemokines and programmed cell death protein-1 (PD-1) expression and enhance antigen presentation. All these regulatory mechanisms synergistically promote the effects of anti-programmed cell death ligand 1 immunotherapy in Setd2-knockout syngeneic mouse models. The SETD2-NR2F1-STAT1 regulatory axis is conserved in human and murine cancers. Finally, cancer patients harboring SETD2 mutations who received ICIs show increased durable clinical benefits and survival. CONCLUSIONS: These findings provide novel insights into the biology of SETD2 inactivation regulation and reveal a new potential therapeutic biomarker for ICIs immunotherapy in various refractory cancers.
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Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Animais , Camundongos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Linfócitos T CD8-Positivos , Biomarcadores , Imunoterapia , Microambiente Tumoral , Fator I de Transcrição COUP/metabolismo , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Histona-Lisina N-Metiltransferase/metabolismoRESUMO
Central precocious puberty (CPP), largely caused by germline mutations in the MKRN3 gene, has been epidemiologically linked to cancers. MKRN3 is frequently mutated in non-small cell lung cancers (NSCLCs) with five cohorts. Genomic MKRN3 aberrations are significantly enriched in NSCLC samples harboring oncogenic KRAS mutations. Low MKRN3 expression levels correlate with poor patient survival. Reconstitution of MKRN3 in MKRN3-inactivated NSCLC cells directly abrogates in vitro and in vivo tumor growth and proliferation. MKRN3 knockout mice are susceptible to urethane-induced lung cancer, and lung cell-specific knockout of endogenous MKRN3 accelerates NSCLC tumorigenesis in vivo. A mass spectrometry-based proteomics screen identified PABPC1 as a major substrate for MKRN3. The tumor suppressor function of MKRN3 is dependent on its E3 ligase activity, and MKRN3 missense mutations identified in patients substantially compromise MKRN3-mediated PABPC1 ubiquitination. Furthermore, MKRN3 modulates cell proliferation through PABPC1 nonproteolytic ubiquitination and subsequently, PABPC1-mediated global protein synthesis. Our integrated approaches demonstrate that the CPP-associated gene MKRN3 is a tumor suppressor.
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Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteína I de Ligação a Poli(A)/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Sequência de Aminoácidos , Animais , Carcinogênese/metabolismo , Carcinogênese/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Células HEK293 , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutação/genética , Ligação Proteica , Biossíntese de Proteínas , Proteínas Proto-Oncogênicas p21(ras)/genética , Reprodutibilidade dos Testes , Análise de Sobrevida , Ubiquitina-Proteína Ligases/química , Ubiquitina-Proteína Ligases/deficiência , Ubiquitina-Proteína Ligases/genética , UretanaRESUMO
Lower warp is required for the single crystal silicon wafers sawn by a fixed diamond wire saw with the thinness of a silicon wafer. The residual stress in the surface layer of the silicon wafer is the primary reason for warp, which is generated by the phase transitions, elastic-plastic deformation, and non-uniform distribution of thermal energy during wire sawing. In this paper, an experiment of multi-wire sawing single crystal silicon is carried out, and the Raman spectra technique is used to detect the phase transitions and residual stress in the surface layer of the silicon wafers. Three different wire speeds are used to study the effect of wire speed on phase transition and residual stress of the silicon wafers. The experimental results indicate that amorphous silicon is generated during resin bonded diamond wire sawing, of which the Raman peaks are at 178.9 cm-1 and 468.5 cm-1. The ratio of the amorphous silicon surface area and the surface area of a single crystal silicon, and the depth of amorphous silicon layer increases with the increasing of wire speed. This indicates that more amorphous silicon is generated. There is both compressive stress and tensile stress on the surface layer of the silicon wafer. The residual tensile stress is between 0 and 200 MPa, and the compressive stress is between 0 and 300 MPa for the experimental results of this paper. Moreover, the residual stress increases with the increase of wire speed, indicating more amorphous silicon generated as well.
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Since Yan's work, incorporation of some lanthanide elements, such as Eu and Nd, into MAPbI3 layer has been proven to be a powerful strategy on improving the permanence of the perovskite solar cells (PSCs). However, a comprehensive configuration has not been given for different lanthanide elements doping while the mechanism has not been clarified. Herein, the incorporation of various lanthanides ions (Ln3+ = Ce3+ , Eu3+ , Nd3+ , Sm3+ , or Yb3+ ) into perovskite films to largely enhance the performance of PSCs is presented. Arising from the enlarged grain size and crystallinity of perovskite film upon Ln3+ ions doping, the efficiency and stability of PSCs are significantly improved. Extraordinarily, PSCs with Ce3+ doping achieve the best performance, with a champion power conversion efficiency (PCE) of 21.67% in contrast to 18.50% for pristine PSCs, and outstanding long-term and UV irradiation stability. Such high performance of PSCs after Ce3+ doping originates from special Ce3+ /Ce4+ redox pair and the unique 4f-5d absorption in the UV region. Finally, the flexible PSCs with low-temperature preparation are explored. Considering the richer deposition of cerium element in the earth and lower price, the findings may provide new opportunities for developing low-cost, highly efficient, air/UV stable, and flexible PSCs.
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Organic-inorganic hybrid perovskite solar cells (PSCs) have achieved rapid progress in this decade. However, the limited solar spectral utilization has restricted the further improvement of performance of the PSCs. One promising approach to solving this problem is utilizing IR to visible upconversion nanoparticles (UCNPs) in the PSC devices. Despite being confined by the lower quantum yield (QY) and smaller absorption cross section of the traditional UCNPs, their application is still a great challenge. In this work, the IR-783 dye-sensitized core/shell NaYF4:Yb3+, Er3+@NaYF4:Yb3+, and Nd3+ UCNPs were synthesized and coupled with plasmonic Au nanorods films. Thereby, the upconversion luminescence (UCL) intensity was enhanced by about 120-fold, whereas the luminescent QY was improved from 0.2 to 1.2%. Then, the composite UCNPs were assembled on the SnO2 layer of the PSCs, which resulted in the power conversion efficiency (PCE) increasing from 19.4 to 20.5% under simulated 100 mw/cm2 AM 1.5G irradiation. Up to now, it is the highest PCE for the PSCs based on various upconversion devices. Under the irradiation of a sun concentrator (1 W/cm2), the PCE of the device can be further improved to 21.1%. In-depth studies indicate that under standard sunlight irradiation, the improvement of PCE is due to both the IR to visible UCL and the scattering effect of the UCNPs. Under irradiation of a sun concentrator, the UCL contributes dominantly to the further improvement of PCE. This work provides an effective method for increasing the luminescent QY utilized in the PSCs and is of great significance for future PSCs that use sunlight concentrator.
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Broadening the near-infrared (NIR) spectrum of device is critical to further improve the power conversion efficiency (PCE) of the perovskite solar cells (PSCs). In this work, novel Cu2CdZn1-xSnS4 (CZTS:Cd) film prepared by thermal evaporation method was employed as the NIR light-harvesting layer to complement the absorption of the perovskite. At the same time, Au nanorods (NRs) were introduced into the hole-transporting layer (HTL) to boost the utilization of CZTS:Cd to NIR light through localized surface plasmon effect. The perovskite/CZTS:Cd and Au NR-integrated PSCs can extend the photoelectric response to 900 nm. And more, the well-matched energy levels between CZTS:Cd and perovskite can effectively extract holes from perovskite and depress the charge carrier recombination. As a result, the champion PSC device insulating with CZTS:Cd and Au NRs demonstrates a remarkably increased PCE from 19.30 to 21.11%. The modified PSC devices also demonstrate highly improved long-time stability. The device retains a PCE of 87% after 500 h even under air with a relative humidity of 85%, implying the superior humidity stability of the devices with CZTS:Cd. This work suggests that perovskite/inorganic-integrated structure is a promising strategy to broaden and boost the NIR response of the PSCs.
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Growing attention has been paid to CsPbIBr2 perovskite solar cells (PSCs) after balancing the band gap and stability features of the interested full-inorganic perovskites. However, their power-conversion efficiency (PCE) still lags behind that of the PSCs using hybrid halide perovskite and how to increase the corresponding PCE is still a challenge. Herein, antisolvents and organic ion surface passivation strategies were systematically applied to precisely control the growth of CsPbIBr2 crystals for constructing a high-quality full-inorganic perovskite film. Through careful adjustments, a CsPbIBr2 film with a pure phase, full coverage, and high crystallinity with preferable (100) orientation was successfully obtained by introducing diethyl ether as the antisolvent followed by guanidinium surface passivation. The optimal CsPbIBr2 film was composed by a large grain with an average size of 950 nm, few grain boundaries, and higher hydrophobic property. Planer PSC using the optimal CsPbIBr2 film and electron-beam-deposited TiO2 compact layer exhibits a PCE of 9.17%, which ranks among the highest PCE range of the reported CsPbIBr2 PSCs. Besides, the designed CsPbIBr2 PSC exhibited good long-term stability, which could maintain 90% of the initial PCE in 40% humidity ambient, which remained constant after heat treatment at 100 °C for 100 h. Based on the optimal CsPbIBr2 film, the flexible and large-area (up to 225 mm2) PSCs were further fabricated. The adopted film improvement methods were further extended to other kinds of full-organic PSCs, which demonstrated the universality of this strategy.
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Photovoltaic devices employing lead halide perovskites as the photoactive layer have attracted enormous attention due to their commercialization potential. Yet, there exists challenges on the way to the practical use of perovskite solar cells (PSCs), such as light stability and current-voltage (J-V ) hysteresis. Inorganic perovskite nanocrystals (IPNCs) are promising candidates for high-performance photovoltaic devices due to their simple synthesis methods, tunable bandgap, and efficient photon downshifting effect for ultraviolet (UV) light blocking and conversion. In this work, CsPbBr3 IPNCs modification could give rise to the vapor phase and solution-processed PSCs with a power conversion efficiency (PCE) of 16.4% and 20.8%, respectively, increased by 11.6% and 5.6% compared to the control devices for more efficient UV utilization and carrier recombination suppression. As far as is known, 11.6% is the most effective enhanced factor for PSCs based on photon downshifting effect inside of devices. The CsPbBr3 layer could also significantly retard light-induced degradation, leading to the lifetime over 100 h under UV illumination for PSCs. Additionally, the modified PSCs exhibit weak hysteresis and multiple colors of fluorescence. These results shed light on the future design of combining a photon downshifting layer and carrier interfacial modification layer in the applications of perovskite optoelectronic devices.
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Perovskite solar cells (PSCs) had received great attention as a result of their recent rapid increasing efficiency. However, the stability of PSCs is still a challenge due to the degradation of the perovskite layer caused by the high-energy ultraviolet (UV) irradiation. Inspired by the luminescent down converting ability for UV blocking and conversion as well as energy transfer between suitable rare earth (RE) ions, a planar CH3NH3PbI3 perovskite solar cell using Sm3+ and Eu3+ co-doped TiO2 electron transfer layer was designed. By optimizing the Sm3+ and Eu3+ doping concentration, the REs co-doped TiO2 ETL combines the advantages of high electron extraction and lower interfacial recombination caused by REs introduction, a power conversion efficiency of 19.01% was obtained. In addition, benefit from the enhanced ability to convert UV light into visible light of the co-doped ETL, the PSCs can sustain higher than at least 80% of the original efficiency over 25â¯days of full sunlight irradiation or after 100â¯h of UV illumination. Moreover, since the low-temperature pulsed laser deposition was adopted in ETL fabrication process, the large area (225â¯mm2) and flexibility devices were further explored, with PCEs of 12.60% and 15.48%, respectively. This work indicates that Sm3+ and Eu3+ co-doped ETLs are effective and promising method to enhance the photovoltaic performance and UV stability of PSCs, which can be further applied in other PSCs with different ETLs and co-doping types.
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Organic-inorganic lead halide perovskite solar cells (PSCs) exhibit spectacular changes in the photovoltaic area, but they still face the challenges of full spectral utilization and photostability under continuous light irradiation. The ultraviolet (UV) part in sunlight could induce oxygen vacancy in the mesoporous TiO2 (m-TiO2) layer, resulting in the degradation of perovskite photoactive films and the rapidly decreased device performance. In this work, we demonstrate that an effective luminescent downconversion material, Eu(TTA)2(Phen)MAA (ETPM), can be used as an interfacial modifier between the m-TiO2 layer and the perovskite photoactive layer to improve the power conversion efficiency (PCE) from 17.00 to 19.07%. The improved device performance can be ascribed to the effective utilization of incident UV light and reduced carrier recombination. Meanwhile, the conversion of the UV light by ETPM could inhibit the stability loss of the device under irradiation. As a result, the modified PSCs can maintain 86% of their initial value under continuous light soaking for 100 h, higher than that of 40% for the control device. This work indicates that the introduction of the luminescent downconversion material ETPM can successfully improve the PCE and photostability of PSCs.
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Studies on comparing the effect of lengthening, isometric and shortening contractions on dystrophin-deficient muscles are unavailable. We hypothesized that different types of contractions lead to different extents to which dystrophin-deficient muscles are injured. For this purpose, we developed protocols for different types of contraction-induced injury to mdx muscles in vitro. Force deficits and percentages of procion orange dye positive fibers were employed to assess the extent of injury to each muscle. Our results revealed that both the lengthening and isometric contractions resulted in significantly greater injury to extensor digitorum longus (EDL) muscles of mdx mice than to that of control (C57BL/6) mice. In contrast, the shortening contractions induced very mild and identical injury to EDL muscles of mdx and C57BL/6 mice. Then another protocol was carried out in vivo to ascertain the effect of shortening contractions on mdx muscles by achillotenotomy. Histological assessment revealed that the triceps surae muscles with excised Achilles tendon (EAT) displayed little and significantly milder injury than the normal ones did. In conclusions, the unloaded shortening contractions induce little injury to mdx muscles. The in vitro protocol for different types of contraction-induced injury is sensitive and reliable.