Effects of irrigation frequency on root growth, nutrients accumulation, yield, and water use efficiency of under micro-sprinkler irrigation.

Micro-sprinkler irrigation has been a promising irrigation method to promote (Burk) F. H. Chen production but their scientific irrigation frequency in improving yield and water use efficiency of remains contradictory and inconclusive.

HIV immune evasin Nef enhances allogeneic CAR T cell potency.

Autologous chimeric antigen receptor (CAR) T cells are a genetically engineered therapy that is highly effective against B cell malignancies and multiple myeloma. However, the length and cost of personalized manufacturing limits access and leaves patients vulnerable to disease progression. Allogeneic cell therapies have the potential to increase patient access and improve treatment outcomes but are limited by immune rejection.

GLUT1 overexpression enhances CAR T cell metabolic fitness and anti-tumor efficacy.

The tumor microenvironment presents many obstacles to effective chimeric antigen receptor (CAR) T cell therapy, including glucose competition from tumor and myeloid cells. Using mouse models of acute lymphoblastic leukemia (ALL), renal cell carcinoma (RCC), and glioblastoma (GBM), we show that enforced expression of the glucose transporter GLUT1 enhances anti-tumor efficacy and promotes favorable CAR-T cell phenotypes for two clinically relevant CAR designs, 19-28z and IL13Rα2-BBz. In the NALM6 ALL model, 19-28z-GLUT1 promotes T stem cell-like memory formation and prolongs survival.

Synthetic dual co-stimulation increases the potency of HIT and TCR-targeted cell therapies.

Chimeric antigen receptor T cells have dramatically improved the treatment of hematologic malignancies. T cell antigen receptor (TCR)-based cell therapies are yet to achieve comparable outcomes. Importantly, chimeric antigen receptors not only target selected antigens but also reprogram T cell functions through the co-stimulatory pathways that they engage upon antigen recognition.

Disruption of SUV39H1-Mediated H3K9 Methylation Sustains CAR T-cell Function.

Unlabelled: Suboptimal functional persistence limits the efficacy of adoptive T-cell therapies. CD28-based chimeric antigen receptors (CAR) impart potent effector function to T cells but with a limited lifespan. We show here that the genetic disruption of SUV39H1, which encodes a histone-3, lysine-9 methyl-transferase, enhances the early expansion, long-term persistence, and overall antitumor efficacy of human CAR T cells in leukemia and prostate cancer models.

Study on Oil Recovery Mechanism of Polymer-Surfactant Flooding Using X-ray Microtomography and Integral Geometry.

Understanding pore-scale morphology and distribution of remaining oil in pore space are of great importance to carry out in-depth tapping of oil potential. Taking two water-wet cores from a typical clastic reservoir in China as an example, X-ray CT imaging is conducted at different experimental stages of water flooding and polymer-surfactant (P-S) flooding by using a high-resolution X-ray microtomography. Based on X-ray micro-CT image processing, 3D visualization of rock microstructure and fluid distribution at the pore scale is achieved.

Generation of T-cell-receptor-negative CD8αβ-positive CAR T cells from T-cell-derived induced pluripotent stem cells.

The production of autologous T cells expressing a chimaeric antigen receptor (CAR) is time-consuming, costly and occasionally unsuccessful. T-cell-derived induced pluripotent stem cells (TiPS) are a promising source for the generation of 'off-the-shelf' CAR T cells, but the in vitro differentiation of TiPS often yields T cells with suboptimal features. Here we show that the premature expression of the T-cell receptor (TCR) or a constitutively expressed CAR in TiPS promotes the acquisition of an innate phenotype, which can be averted by disabling the TCR and relying on the CAR to drive differentiation.

ULK1/2 Constitute a Bifurcate Node Controlling Glucose Metabolic Fluxes in Addition to Autophagy.

Metabolic reprogramming is fundamental to biological homeostasis, enabling cells to adjust metabolic routes after sensing altered availability of fuels and growth factors. ULK1 and ULK2 represent key integrators that relay metabolic stress signals to the autophagy machinery. Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).

AMP as a low-energy charge signal autonomously initiates assembly of AXIN-AMPK-LKB1 complex for AMPK activation.

The AMP-activated protein kinase (AMPK) is a master regulator of metabolic homeostasis by sensing cellular energy status. AMPK is mainly activated via phosphorylation by LKB1 when cellular AMP/ADP levels are increased. However, how AMP/ADP brings about AMPK phosphorylation remains unclear.

Revealing a steroid receptor ligand as a unique PPARγ agonist.

Peroxisome proliferator-activated receptor gamma (PPARγ) regulates metabolic homeostasis and is a molecular target for anti-diabetic drugs. We report here the identification of a steroid receptor ligand, RU-486, as an unexpected PPARγ agonist, thereby uncovering a novel signaling route for this steroid drug. Similar to rosiglitazone, RU-486 modulates the expression of key PPARγ target genes and promotes adipocyte differentiation, but with a lower adipogenic activity.