Predictors of discordance between CT-derived fractional flow reserve (CT-FFR) and △CT-FFR in deep coronary myocardial bridging.

OBJECTIVE: To compare the performance between CT-derived fractional flow reserve (CT-FFR) and ΔCT-FFR measurements in patients with deep myocardial bridging (MB) along the left anterior descending artery, and explore the potential predictors of discordance. METHODS: 175 patients with deep MB who underwent coronary computed tomography angiography (CCTA) and CT-FFR assessment were included. Clinical, anatomical and atherosclerotic variables were compared between patients with concordant and discordant CT-FFR and ΔCT-FFR. RESULTS: 30.9 % patients were discordantly classified, in which 94.4 % patients were classified as CT-FFR+/△CT-FFR-. The discordant group showed significantly higher upstream stenosis degree, distance from MB to the aorta, △CT-FFR (P 0.007, 0.009 and 0.002, respectively), and lower CT-FFR (P < 0.001). In multivariate analysis, upstream stenosis degree (P 0.023, OR 1.628, 95 % CI: 1.068-2.481) and distance from MB to the aorta (P 0.001, OR 1.04, 95 % CI: 1.016-1.064) were independent predictors for discordance between CT-FFR and ΔCT-FFR. CONCLUSION: The discordance between CT-FFR and ΔCT-FFR measurements underscores the challenges in clinical decision-making, necessitating tailored approaches for MB evaluation.

Hole-Pinned Defect Clusters for a Large Dielectric Constant up to GHz in Zinc and Niobium Codoped Rutile SnO2.

High permittivity materials for a gigahertz (GHz) communication technology have been actively sought for some time. Unfortunately, in most materials, the dielectric constant starts to drop as frequencies increase through the megahertz (MHz) range. In this work, we report a large dielectric constant of ∼800 observed in defect-mediated rutile SnO2 ceramics, which is nearly frequency and temperature independent over the frequency range of 1 mHz to 35 GHz and temperature range of 50-450 K. Experimental and theoretical investigations demonstrate that the origin of the high dielectric constant can be attributed to the formation of locally well-defined Zn2+-Nb4+ defect clusters, which create hole-pinned defect dipoles. We believe that this work provides a promising strategy to advance dipole polarization theory and opens up a direction for the design and development of high frequency, broadband dielectric materials for use in future communication technology.

Peptide PD29 treats bleomycin-induced pulmonary fibrosis by inhibiting the TGF-ß/smad signaling pathway.

Pulmonary fibrosis (PF) is an end-stage change in lung disease characterized by fibroblast proliferation, massive extracellular matrix (ECM) aggregation with inflammatory damage, and severe structural deterioration. PD29 is a 29-amino acid peptide which has the potential to alleviate PF pathogenesis via three mechanisms: anti-angiogenesis, inhibition of matrix metalloproteinase activities, and inhibition of integrins. In this study, fibrotic lung injuries were induced in SD rats by a single intratracheal instillation of 5 mg/kg bleomycin (BLM). Then, these rats were administered 7.5, 5, or 2.5 mg/kg PD29 daily for 30 days. BLM induced-syndromes including structure distortion, excessive deposition of ECM, excessive inflammatory infiltration, and pro-inflammatory cytokine release were used to evaluate the protective effect of PD-29. Oxidative stress damage in lung tissues was attenuated by PD29 in a dose-dependent manner. The expression of TGF-ß1 and the phosphorylation of Smad-2/-3-its downstream targets-were enhanced by BLM and weakened by PD29. In vitro, PD29 inhibited TGF-ß1-induced epithelial-mesenchymal transition (EMT) and transformation in A549 cells and mouse primary fibroblasts into myofibroblasts. In summary, PD29 reversed EMT and transformation of fibroblasts into myofibroblasts in vitro and prevented PF in vivo possibly by suppressing the TGF-ß1/Smad pathway.

Photovoltaic Effect of a Ferroelectric-Luminescent Heterostructure under Infrared Light Illumination.

In this report, a ferroelectric-luminescent heterostructure is designed to convert infrared light into electric power. We use BiFeO3 (BFO) as the ferroelectric layer and Y2O3:Yb,Tm (YOT) as the upconversion layer. Different from conventional ferroelectric materials, this heterostructure exhibits switchable and stable photovoltaic effects under 980 nm illumination, whose energy is much lower than the band gap of BFO. The energy transfer mechanism in this heterostructure is therefore studied carefully. It is found that a highly efficient nonradiative energy transfer process from YOT to BFO plays a critical role in achieving the below-band-gap photon-excited photovoltaic effects in this heterostructure. Our results also indicate that by introducing asymmetric electrodes, both the photovoltage and photocurrent are further enhanced when the built-in field and the depolarization field are aligned. The construction of ferroelectric-luminescent heterostructure is consequently proposed as a promising route to enhance the photovoltaic effects of ferroelectric materials by extending the absorption of the solar spectrum.

Recombination of a dual-CAR-modified T lymphocyte to accurately eliminate pancreatic malignancy.

BACKGROUND: The therapeutic application of T cells endowing with chimeric antigen receptors (CARs) is faced with "on-target, off-tumor" toxicity against solid tumors, particularly in the treatment of the pancreatic cancer. To our best knowledge, the pancreatic cancer cell line AsPC-1 often highly expressed some distinct tumor-associated antigens, such as carcino-embryonic antigen (CEA) and mesothelin (MSLN). Therefore, in this research, we have characterized dual-receptor CAR-modified T cells (dCAR-T) that exert effective and safe cytotoxicity against AsPC-1 cells. METHODS: Based on the dual signaling pathway of wild T cells, we designed a novel dCAR diagram specific for CEA and MSLN, which achieved comparable activity relative to that of conventional CAR-T cells (CEA-CAR T or MSLN-CAR T). In this dCAR, a tandem construct containing two physically separate structures, CEA-CD3ζ and MSLN-4/1BB signaling domains were effectively controlled with tumor antigens CEA and MSLN, respectively. Finally, the activity of dCAR-T cells has been verified via in vitro and in vivo experiments. RESULTS: In the presence of cognate tumor cells (AsPC-1) expressing both CEA and MSLN, dCAR-T cells exerted high anti-tumor activity relative to that of other single-receptor CAR-T cells bearing only one signaling pathway (e.g., Cζ-CAR and MBB-CAR). In a xenograft model, dCAR-T cells significantly inhibited the growth of AsPC-1 cells yet no effect on the growth of non-cognate tumor cells. Furthermore, the released cytokines and T cell persistence in mice were comparable with that of conventional CAR-T cells, obtaining specific and controllable cytotoxicity. CONCLUSIONS: A novel type of CAR-T cells, termed dCAR-T, was designed with specific activities, that is, significant cytotoxicity for two antigen-positive tumor cells yet no cytotoxicity for single antigen-positive tumor cells. Dual-targeted CAR-T cells can be precisely localized at the tumor site and can exert high cytotoxicity against tumor cells, alleviating "on-target, off-tumor" toxicity and enabling accurate application of CAR-T cell therapy.

Bimetallic Ions Codoped Nanocrystals: Doping Mechanism, Defect Formation, and Associated Structural Transition.

Ionic codoping offers a powerful approach for modifying material properties by extending the selection of potential dopant ions. However, it has been a major challenge to introduce certain ions that have hitherto proved difficult to use as dopants (called "difficult-dopants") into crystal structures at high concentrations, especially through wet chemical synthesis. Furthermore, the lack of a fundamental understanding of how codopants are incorporated into host materials, which types of defect structures they form in the equilibrium state, and what roles they play in material performance, has seriously hindered the rational design and development of promising codoped materials. Here we take In3+ (difficult-dopants) and Nb5+ (easy-dopants) codoped anatase TiO2 nanocrystals as an example and investigate the doping mechanism of these two different types of metal ions, the defect formation, and their associated impacts on high-pressure induced structural transition behaviors. It is experimentally demonstrated that the dual mechanisms of nucleation and diffusion doping are responsible for the synergic incorporation of these two dopants and theoretically evidenced that the defect structures created by the introduced In3+, Nb5+ codopants, their resultant Ti3+, and oxygen vacancies are locally composed of both defect clusters and equivalent defect pairs. These formed local defect structures then act as nucleation centers of baddeleyite- and α-PbO2-like metastable polymorphic phases and induce the abnormal trans-regime structural transition of codoped anatase TiO2 nanocrystals under high pressure. This work thus suggests an effective strategy to design and synthesize codoped nanocrystals with highly concentrated difficult-dopants. It also unveils the significance of local defect structures on material properties.

The Formation of Defect-Pairs for Highly Efficient Visible-Light Catalysts.

Highly efficient visible-light catalysts are achieved through forming defect-pairs in TiO2 nanocrystals. This study therefore proposes that fine-tuning the chemical scheme consisting of charge-compensated defect-pairs in balanced concentrations is a key missing step for realizing outstanding photocatalytic performance. This research benefits photocatalytic applications and also provides new insight into the significance of defect chemistry for functionalizing materials.

Ni2+ doped indium oxide nanocubes: doped contents inducing transferring of their intrinsic magnetisms.

A series of Ni2+ doped indium oxide nanocubes with different Ni2+ contents (nominally from 3 at.% to 20 at.%) were prepared by direct solvothermal method. We found that the highest Ni2+ doped percentage was 20 at.% in the experiment and crystalline sizes of these Ni2+ doped indium oxide specimens linearly increased with increments of doped contents and then decreased. Meanwhile, their magnetisms were also transferred from ferromagnetism to paramagnetic properties due to the stronger Ni-O-Ni paramagnetic chemical bonds. HRTEM, SAED and XRD further confirmed their magnetic properties were intrinsic and not caused by second impure phases.