Fluorophores with emission in the second near‐infrared (NIR‐II) window have displayed salient advantages for biomedical applications. However, exploration of new luminogens with high NIR‐II ...fluorescent brightness is still challenging. Herein, based on the “ring‐fusion” strategy, a series of heteroatom‐inserted rigid‐planar cores is proposed to achieve the bathochromic NIR‐II fluorophores with aggregation‐induced emission (AIE) performance. Interestingly, one of the representative fluorophores, 4,4′‐(5,5′‐(1,2,5thiadiazolo3,4‐idithieno2,3‐a:3′,2′‐cphenazine‐8,12‐diyl)bis(4‐octylthiophene‐5,2‐diyl))bis(N,N‐diphenylaniline) (TTQiT), enjoys a maximum emission beyond 1100 nm because of the efficiently narrowed energy bandgap by electron‐rich sulfur‐atom‐inserted core, which is verified by theoretical calculation. Taking advantage of the bright NIR‐II emission of TTQiT nanoparticles, the desirable in vivo NIR‐II imaging with high signal‐to‐background ratios is successfully performed and a long‐term stem cell tracking in the detection of acute lung injury is further realized. Therefore, it is anticipated that this work will provide a promising molecular engineering strategy to enrich the scope of NIR‐II fluorophores for catering to diverse demands in biomedical applications.
A heteroatom‐inserted electron delocalization (HEED) strategy is facilitated to construct a series of second near‐infrared (NIR‐II) fluorophores. One representative AIEgen (TTQiT) displays a maximum emission wavelength beyond 1100 nm with desirable fluorescent brightness, which is successfully used as the NIR‐IIa cell trackers to dynamically detect the homing of stem cells in mice with acute lung injury.
Natural killer (NK) cells are an emerging cellular immunotherapy for patients with acute myeloid leukemia (AML); however, the best approach to maximize NK cell antileukemia potential is unclear. ...Cytokine-induced memory-like NK cells differentiate after a brief preactivation with interleukin-12 (IL-12), IL-15, and IL-18 and exhibit enhanced responses to cytokine or activating receptor restimulation for weeks to months after preactivation. We hypothesized that memory-like NK cells exhibit enhanced antileukemia functionality. We demonstrated that human memory-like NK cells have enhanced interferon-γ production and cytotoxicity against leukemia cell lines or primary human AML blasts in vitro. Using mass cytometry, we found that memory-like NK cell functional responses were triggered against primary AML blasts, regardless of killer cell immunoglobulin-like receptor (KIR) to KIR-ligand interactions. In addition, multidimensional analyses identified distinct phenotypes of control and memory-like NK cells from the same individuals. Human memory-like NK cells xenografted into mice substantially reduced AML burden in vivo and improved overall survival. In the context of a first-in-human phase 1 clinical trial, adoptively transferred memory-like NK cells proliferated and expanded in AML patients and demonstrated robust responses against leukemia targets. Clinical responses were observed in five of nine evaluable patients, including four complete remissions. Thus, harnessing cytokine-induced memory-like NK cell responses represents a promising translational immunotherapy approach for patients with AML.
Strong periodic driving with light offers the potential to coherently manipulate the properties of quantum materials on ultrafast timescales. Recently, strategies have emerged to drastically alter ...electronic and magnetic properties by optically inducing non-trivial band topologies
, emergent spin interactions
and even superconductivity
. However, the prospects and methods of coherently engineering optical properties on demand are far less understood
. Here we demonstrate coherent control and giant modulation of optical nonlinearity in a van der Waals layered magnetic insulator, manganese phosphorus trisulfide (MnPS
). By driving far off-resonance from the lowest on-site manganese d-d transition, we observe a coherent on-off switching of its optical second harmonic generation efficiency on the timescale of 100 femtoseconds with no measurable dissipation. At driving electric fields of the order of 10
volts per metre, the on-off ratio exceeds 10, which is limited only by the sample damage threshold. Floquet theory calculations
based on a single-ion model of MnPS
are able to reproduce the measured driving field amplitude and polarization dependence of the effect. Our approach can be applied to a broad range of insulating materials and could lead to dynamically designed nonlinear optical elements.
Osteoporosis is the second most-prevalent epidemiologic disease in the aging population worldwide. Cross-sectional and retrospective evidence indicates that tea consumption can mitigate bone loss and ...reduce risk of osteoporotic fractures. Tea polyphenols enhance osteoblastogenesis and suppress osteoclastogenesis in vitro. Previously, we showed that (-)-epigallocatechin-3-gallate (EGCG), one of the green tea polyphenols, increased osteogenic differentiation of murine bone marrow mesenchymal stem cells (BMSCs) by increasing the mRNA expression of osteogenesis-related genes, alkaline phosphatase activity and, eventually, mineralization. We also found that EGCG could mitigate bone loss and improve bone microarchitecture in ovariectomy-induced osteopenic rats, as well as enhancing bone defect healing partially via bone morphogenetic protein 2 (BMP2). The present study investigated the effects of EGCG in human BMSCs. We found that EGCG, at concentrations of both 1 and 10 µmol/L, can increase mRNA expression of BMP2, Runx2, alkaline phosphatase (ALP), osteonectin and osteocalcin 48 h after treatment. EGCG increased ALP activity both 7 and 14 days after treatment. Furthermore, EGCG can also enhance mineralization two weeks after treatment. EGCG without antioxidants also can enhance mineralization. In conclusion, EGCG can increase mRNA expression of BMP2 and subsequent osteogenic-related genes including Runx2, ALP, osteonectin and osteocalcin. EGCG further increased ALP activity and mineralization. Loss of antioxidant activity can still enhance mineralization of human BMSCs (hBMSCs).
Acute lung injury (ALI) is a life-threatening respiratory condition characterized by severe inflammation and lung tissue damage, frequently causing rapid respiratory failure and long-term ...complications. The microRNA let-7a-5p is involved in the progression of lung injury, inflammation, and fibrosis by regulating immune cell activation and cytokine production. This study aims to use an innovative cellular electroporation platform to generate extracellular vesicles (EVs) carring let-7a-5p (EV-let-7a-5p) derived from transfected Wharton's jelly-mesenchymal stem cells (WJ-MSCs) as a potential gene therapy for ALI.
A cellular nanoporation (CNP) method was used to induce the production and release of EV-let-7a-5p from WJ-MSCs transfected with the relevant plasmid DNA. EV-let-7a-5p in the conditioned medium were isolated using a tangential flow filtration (TFF) system. EV characterization followed the minimal consensus guidelines outlined by the International Society for Extracellular Vesicles. We conducted a thorough set of therapeutic assessments, including the antifibrotic effects using a transforming growth factor beta (TGF-β)-induced cell model, the modulation effects on macrophage polarization, and the influence of EV-let-7a-5p in a rat model of hyperoxia-induced ALI.
The CNP platform significantly increased EV secretion from transfected WJ-MSCs, and the encapsulated let-7a-5p in engineered EVs was markedly higher than that in untreated WJ-MSCs. These EV-let-7a-5p did not influence cell proliferation and effectively mitigated the TGF-β-induced fibrotic phenotype by downregulating SMAD2/3 phosphorylation in LL29 cells. Furthermore, EV-let-7a-5p regulated M2-like macrophage activation in an inflammatory microenvironment and significantly induced interleukin (IL)-10 secretion, demonstrating their modulatory effect on inflammation. Administering EVs from untreated WJ-MSCs slightly improved lung function and increased let-7a-5p expression in plasma in the hyperoxia-induced ALI rat model. In comparison, EV-let-7a-5p significantly reduced macrophage infiltration and collagen deposition while increasing IL-10 expression, causing a substantial improvement in lung function.
This study reveals that the use of the CNP platform to stimulate and transfect WJ-MSCs could generate an abundance of let-7a-5p-enriched EVs, which underscores the therapeutic potential in countering inflammatory responses, fibrotic activation, and hyperoxia-induced lung injury. These results provide potential avenues for developing innovative therapeutic approaches for more effective interventions in ALI.
In this letter, we present a novel step spin-orbit torque magnetic random access memory (SOT-MRAM) cell structure and its switching behavior. A special stop-on-MgO etch etches away the hard mask and ...the pinned layer while retaining the free layer (FL) and MgO as part of the cell. The extended Ta/CoFeB/MgO layer is proved to be more tolerant to the etching non-uniformity of the Ta nanowire and improve etching yield. Although etching stops on MgO, the FL underneath the thin MgO has been rendered non-magnetic by the etching process. Recessed Cu pads were added to the Ta nanowire, which substantially reduces the overall resistance of the Ta nanowire. The general switching behavior of the step SOT-MRAM cells, such as pulse-width and temperature dependence of the switching currents, resembles that of a spin-transfer torque MRAM cell.
A low-cost fabrication process of Hf 1-x Zr x O 2 (HZO) nonvolatile memory (NVM) was proposed and its characteristics were investigated. We successfully fabricated a ferroelectric tunnel junction ...(FTJ) device with tunable conductance for neural network applications. The proposed FTJ device exhibits excellent performances, such as large conductance ratio of ~40 for a 500-ns pulse and thus satisfied low-power consumption of write pulse (1 fJ per bit) and fast write speed (<; 500 ns) requirements. Furthermore, we revealed that the metal-ferroelectric-insulator-semiconductor structure had a higher tunneling electroresistance ratio than the metal-ferroelectric-insulator-metalstructure. Moreover, the polarization operation of our FTJ devices achieved low-power analog-like conductance transition, multilevel operation, and even endurance characteristics is promising. These results demonstrate that the FTJ has high potential to be an ideal emerging memory for neuromorphic computing. Therefore, HZO-based devices are promising materials in neural network applications for next-generation devices.
•VEW-MWPLS is proposed to enhance the prediction performance of NOx emission.•With adjustable forgetting factor, VEW-MWPLS can change modeling data window.•An efficient updated scheme with detailed ...derivations is provided.•Computational efficiency of VEW-MWPLS and past methods are analyzed and compared.
The efficiency of selective catalytic reduction denitrification heavily depends on the amount of ammonia injection, which is determined by the emission of nitrogen oxides (NOx) in flue gas. To accurately predict NOx emission of the coal-fired boiler with strong variable correlations, nonlinear and time-varying characteristics for determining the amount of injected ammonia, a soft sensor modeling method based on the moving window partial least squares (MWPLS) and locally weighted regression, referred to as variable exponentially weighted MWPLS (VEW-MWPLS), is proposed. It adjusts the window size in disguised form by automatically strengthen or weaken the information in the selected window according to the prediction errors of the current model. In this work, with the added new sample and the removed old sample, a series of rank-1 modification formulations are used to calculate both, the means and standard deviations among the input and output variables and the covariance and cross-covariance matrices so that a quick and adaptive update can be done for the PLS model. The numerical results have demonstrated that VEW-MWPLS algorithm can reduce the mean and standard deviation of prediction errors by one order of magnitude, and reduce the computational complexity by two orders of magnitude when being compared with other algorithms. Thus the proposed VEW-MWPLS is more suitable for predicting NOx emission online.
Photodetectors based on reduced graphene oxide (rGO) have attracted much attention owing to their simple and low‐cost fabrication process. However, the aggregation and defects of rGO flakes still ...limit the performance of rGO photodetectors. Controlling the composition of rGO has become a vital factor for its prospective applications. For example, the interconnection between rGO and polymers for modified morphologies of rGO films leads to an enhanced performance of devices. In this work, a practical approach to engineer surface uniformity and enhance the performance of a photodetector by modifying the rGO film with hydrophilic polymers poly(vinyl alcohol) (PVA) is reported. Compared with the rGO photodetector, the on/off ratio for the PVA/rGO photodetector shows 3.5 times improvement, and the detectivity shows 53% enhancement even when the photodetector is operated at a low bias of 0.3 V. This study provides an effective route to realize PVA/rGO photodetectors with a low‐power operation which shows promising opportunities for the future development of green systems.
A practical approach to enhance the performance of a reduced graphene oxide (rGO) photodetector by modifying the rGO film with poly(vinyl alcohol) (PVA) is reported. Compared with the rGO photodetector, the on/off ratio for the PVA/rGO photodetector shows 3.5 times improvement, and the detectivity shows 53% enhancement at a low operating bias of 0.3 V.
We designed and manufactured a pneumatic-driven robotic passive gait training system (PRPGTS), providing the functions of body-weight support, postural support, and gait orthosis for patients who ...suffer from weakened lower limbs. The PRPGTS was designed as a soft-joint gait training rehabilitation system. The soft joints provide passive safety for patients. The PRPGTS features three subsystems: a pneumatic body weight support system, a pneumatic postural support system, and a pneumatic gait orthosis system. The dynamic behavior of these three subsystems are all involved in the PRPGTS, causing an extremely complicated dynamic behavior; therefore, this paper applies five individual interval type-2 fuzzy sliding controllers (IT2FSC) to compensate for the system uncertainties and disturbances in the PRGTS. The IT2FSCs can provide accurate and correct positional trajectories under passive safety protection. The feasibility of weight reduction and gait training with the PRPGTS using the IT2FSCs is demonstrated with a healthy person, and the experimental results show that the PRPGTS is stable and provides a high-trajectory tracking performance.
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