Search

CD28 and CTLA4 are T cell coreceptors that competitively engage B7 ligands CD80 and CD86 to control adaptive immune responses. While the role of CTLA4 in restraining CD28 costimulatory signaling is well-established, the mechanism has remained unclear. Here, we report that human T cells acquire antigen-presenting-cell (APC)-derived B7 ligands and major histocompatibility complex (MHC) via trogocytosis through CD28:B7 binding. Acquired MHC and B7 enabled T cells to autostimulate, and this process was limited cell-intrinsically by CTLA4, which depletes B7 ligands trogocytosed or endogenously expressed by T cells through cis-endocytosis. Extending this model to the previously proposed extrinsic function of CTLA4 in human regulatory T cells (Treg), we show that blockade of either CD28 or CTLA4 attenuates Treg-mediated depletion of APC B7, indicating that trogocytosis and CTLA4-mediated cis-endocytosis work together to deplete B7 from APCs. Our study establishes CTLA4 as a cell-intrinsic molecular sink that limits B7 availability on the surface of T cells, with implications for CTLA4-targeted therapy.

B7 ligands (CD80 and CD86), expressed by professional antigen-presenting cells (APCs), activate the main co-stimulatory receptor CD28 on T cells in trans. However, in peripheral tissues, APCs expressing B7 ligands are relatively scarce. This raises the questions of whether and how CD28 co-stimulation occurs in peripheral tissues. Here, we report that CD8+ T cells displayed B7 ligands that interacted with CD28 in cis at membrane invaginations of the immunological synapse as a result of membrane remodeling driven by phosphoinositide-3-kinase (PI3K) and sorting-nexin-9 (SNX9). cis-B7:CD28 interactions triggered CD28 signaling through protein kinase C theta (PKCθ) and promoted CD8+ T cell survival, migration, and cytokine production. In mouse tumor models, loss of T cell-intrinsic cis-B7:CD28 interactions decreased intratumoral T cells and accelerated tumor growth. Thus, B7 ligands on CD8+ T cells can evoke cell-autonomous CD28 co-stimulation in cis in peripheral tissues, suggesting cis-signaling as a general mechanism for boosting T cell functionality.

As a major infectious disease in chickens, Newcastle disease virus (NDV) causes considerable economic losses in the poultry industry, especially in developing countries where there is limited access to effective vaccination. Therefore, enhancing resistance to the virus in commercial chickens through breeding is a promising way to promote poultry production. In this study, we investigated gene expression changes at 2 and 6 days post inoculation (dpi) at day 21 with a lentogenic NDV in a commercial egg-laying chicken hybrid using RNA sequencing analysis. By comparing NDV-challenged and non-challenged groups, 526 differentially expressed genes (DEGs) (false discovery rate (FDR) < 0.05) were identified at 2 dpi, and only 36 at 6 dpi. For the DEGs at 2 dpi, Ingenuity Pathway Analysis predicted inhibition of multiple signaling pathways in response to NDV that regulate immune cell development and activity, neurogenesis, and angiogenesis. Up-regulation of interferon induced protein with tetratricopeptide repeats 5 (IFIT5) in response to NDV was consistent between the current and most previous studies. Sprouty RTK signaling antagonist 1 (SPRY1), a DEG in the current study, is in a significant quantitative trait locus associated with virus load at 6 dpi in the same population. These identified pathways and DEGs provide potential targets to further study breeding strategy to enhance NDV resistance in chickens.

Two-dimensional Ruddlesden–Popper (RP) tin halide perovskites have recently shown promise in solar energy conversion applications owing to their low-toxicity and low-cost processability. However, RP tin halide perovskites typically consist of multiple phases with enormously disordered crystal orientation, lowering their power conversion efficiency. Herein, we show a new method to prepare phase-pure RP tin hybrid perovskite films by fluorinating the conventionally used spacer cation C6H5CH2NH3+ (abbreviated as FBE+). This solvophobic engineering strategy decreases the interaction among spacer cations and solvent molecules to induce the self-assembly of FBE+ cations into micelles. These micelles in the solvent capture tin iodide components, forming crystal nuclei. This "simultaneous" crystallization mode leads to uniformly distributed nuclei and further results in a phase-pure RP perovskite with vertical crystal orientation. The resultant phase pure FBE2FA3Sn4I13 perovskite exhibits an improved carrier mobility and much reduced trap density, which are favourable for solar energy conversion applications. A power conversion efficiency of 9.25% was achieved for the FBE2FA3Sn4I13 perovskite solar cell, which is among the highest efficiencies reported for state-of-the-art two-dimensional RP tin hybrid perovskite cells. [ABSTRACT FROM AUTHOR]

The challenges of instability and surface defects in CsPbBrxI3‐x nanocrystals (NCs) pose significant limitations on their potential application in high‐performance pure‐red perovskite light‐emitting diodes (PeLEDs). Herein, a synergistic strategy of divalent cation (Zn2+) doping and anion (Te2−) passivation is proposed to solve these issues. Density functional theory analysis reveals that the synergistic effect can not only reduce the formation energy of CsPbBrxI3‐x NCs but also increase theiodide vacancy defect formation energy of CsPbBrxI3‐x NCs. Consequently, the optimized Zn2+/Te2− co‐modified CsPbBrxI3‐x NCs exhibit significantly enhanced stability with a near‐unity photoluminescence efficiency. Pure‐red PeLEDs based on these CsPbBrxI3‐x NCs possess outstanding spectral stability with a maximum external quantum efficiency and luminance of 16.1% and 1397.2 cd m−2, respectively. This synergistic strategy provides a new approach for enhancing the performance of mixed halide perovskite NCs and the corresponding optoelectronic devices. [ABSTRACT FROM AUTHOR]

Richter's transformation (RT) is a progression of chronic lymphocytic leukemia (CLL) to aggressive lymphoma. MGA (Max gene associated), a functional MYC suppressor, is mutated at 3% in CLL and 36% in RT. However, genetic models and molecular mechanisms of MGA deletion that drive CLL to RT remain elusive. We established an RT mouse model by knockout of Mga in the Sf3b1/Mdr CLL model using CRISPR-Cas9 to determine the role of Mga in RT. Murine RT cells exhibited mitochondrial aberrations with elevated oxidative phosphorylation (OXPHOS). Through RNA sequencing and functional characterization, we identified Nme1 (nucleoside diphosphate kinase) as an Mga target, which drives RT by modulating OXPHOS. Given that NME1 is also a known MYC target without targetable compounds, we found that concurrent inhibition of MYC and electron transport chain complex II substantially prolongs the survival of RT mice in vivo. Our results suggest that the Mga-Nme1 axis drives murine CLL-to-RT transition via modulating OXPHOS, highlighting a potential therapeutic avenue for RT. Editor's summary: Richter's transformation (RT) involves the progression of chronic lymphocytic leukemia (CLL) to a more aggressive lymphoma with poor outcomes. Understanding the transition into RT is key to more targeted therapeutic strategies. Iyer et al. examined the role of the MYC suppressor MGA, which is differentially expressed in RT, in an in vivo CLL model with MGA dysfunction. MGA loss resulted in increased mitochondrial function and reactive oxygen species and led to aberrant cell morphology and up-regulated MYC as commonly observed in patients. Combined inhibition of MYC and mitochondrial respiration prolonged in vivo survival in this model, highlighting potential therapeutic strategies for RT with this genetic profile. —Catherine Charneski [ABSTRACT FROM AUTHOR]

Enhancing genetic resistance of chickens to Newcastle Disease Virus (NDV) provides a promising way to improve poultry health, and to alleviate poverty and food insecurity in developing countries. In this study, two inbred chicken lines with different responses to NDV, Fayoumi and Leghorn, were challenged with LaSota NDV strain at 21 days of age. Through transcriptome analysis, gene expression in spleen at 2 and 6 days post-inoculation was compared between NDV-infected and control groups, as well as between chicken lines. At a false discovery rate

Due to its complex nonlinear, underdriven, and strongly coupled characteristics, the tower crane will cause the load to swing violently when working, which will cause the tower crane to tip over in serious cases, and there exists a huge safety hazard. In this article, a new artificial neural network sliding mode control method is designed for the control problems of tower crane lifting in position and load swing prevention, which has strong robustness to disturbances and unmodeled dynamics, and ensures that the tower crane lifting is accurately tracked in position and suppresses the load swing at the same time. First, a nonlinear dynamics model of a five-degree-of-freedom tower crane considering the actual working conditions is established. Aiming at the problem that it is difficult to effectively control the nonlinear model of the tower crane system, a new neural sliding mode controller and compensation controller are designed based on the sliding mode control theory and using radial basis function neural network. The neural sliding mode controller is used to approximate the sliding mode equivalent controller with uncertainty and strong nonlinearity, and the compensation controller realizes the compensation of the neural sliding mode controller for the difference between the system control inputs and the uncertainty of the system. The convergence and stability of the proposed control system is rigorously demonstrated using the Lyapunov stability theory. Simulation studies have been carried out to verify the correctness of the model established in this article, as well as the excellent control performance of the control system and the ability to deal with system uncertainty, proving its strong robustness. [ABSTRACT FROM AUTHOR]

The goal of this study was to research the effects of Lactobacillus buchneri L3-9 and its extracellular products on growth, immunity, intestinal microorganisms, and disease resistance to Aeromonas hydrophila in grass carp. A total of 120 fish (80–90 g) were distributed into 12 aquariums (10 fish/aquarium) in three replicates and fed 1% of their body weight for 21 days. The grass carp were fed four different diets: a control (group C), a diet supplemented with 1 × 106 cell g−1 of L. buchneri L3-9 (group B), a diet supplemented with extracellular products of L. buchneri L3-9 (group E), and a diet supplemented with L. buchneri L3-9 and the extracellular products (group BE). Compared with the control diet, the B, E, and BE diets increased the weight gain rate by 4.49%, 2.59%, and 4.38%, respectively (p < 0.05), and significantly decreased the feed conversion ratio by 0.72, 0.57, and 0.76, respectively (p < 0.05). Groups B, BE, and E showed significant decreases in mortality, with values of 26.67%, 16.67%, and 23.33%, respectively (p < 0.05). Group B showed a significant increase in superoxide dismutase (SOD) activity and total antioxidant capacity (T-AOC) and decrease in malondialdehyde (MDA) content compared to the control group (p < 0.05). The highest catalase (CAT) activity was found in group E (p < 0.05). In group B, the expression of the gut proinflammatory gene TNF-α was downregulated (p < 0.05), and the expression of anti-inflammatory genes, including TGF-β1, IL-10, and Tlr-8, was upregulated compared to that in the control group (p < 0.05). Groups BE and E showed an increased abundance of Lactobacillaceae. Additionally, a drastic decrease in the abundance of pathogenic bacteria such as Aeromonadaceae and Enterobacteriaceae was in these groups compared to the control group. In conclusion, L. buchneri L3-9 and its extracellular products could improve the growth performance, immune responses, and resistance to A. hydrophila in grass carp. This study provides insights for the development and application of microecological preparations. [ABSTRACT FROM AUTHOR]

Lanthanide ions, as dopants, have evoked widespread research interest owing to the rich optical, magnetic, and electrical properties, but their luminescent intensity is always limited by typical concentration quenching. Herein, a holmium‐based double perovskite of Cs2NaHoCl6 is reported, which surprisingly breaks through this barrier and achieves efficient red‐NIR emission by virtue of the large unit cell, low phonon energy, high content of activators, and cross relaxation phenomenon between Ho3+. The heavy Ho3+ also endows the intriguing half‐metallic nature with a down‐spin conducting band and an up‐spin insulating band. After performing ion doping on crystallographic sites of Na+ and Ho3+, the photoluminescence quantum yield of such red‐NIR emitter under 450 nm excitation is dramatically promoted to 82.3%, benefiting from the improved crystal field environment that alleviates the parity forbidden rule and suppresses non‐radiative recombination loss. Furthermore, the heat‐favorable phonon‐assisted population processes enable the robust photostability against thermal quenching. By combining a 450 nm chip, the red‐NIR light‐emitting diodes are fabricated, in which the wide‐coverage NIR emissions are ideally suited for medical light source, night vision, nondestructive examination, and transmission imaging. It is believed that this work will open an avenue for enhancing the fluorescence of lanthanide ions and developing advanced spintronic materials. [ABSTRACT FROM AUTHOR]