Disodium terephthalate and its various derivatives are synthesized via simple acid‐base chemistry for anode materials in Na ion batteries. They show excellent electrochemical performance, including ...little capacity fading over 90 cycles, ideal redox potential, and excellent rate performance, making them promising candidates for Na ion batteries.
Designing chiral channels in organic frameworks presents an ongoing challenge due to the intricate control of size, shape, and functionality required. A novel approach is presented, which crafts ...enantiomeric chiral channels in metal‐peptide networks (MPNs) by integrating short foldamer ligands with CuI clusters. The MPN structure serves as a 3D blueprint for host‐guest chemistry, fostering modular substitution to refine chiral channel properties at the atomic scale. Incorporating hydrogen bond networks augments guest molecule interactions with the channel surface. This approach expedites enantiomer discrimination in racemic mixtures and incites adaptable guest molecules to take on specific axially chiral conformations. Distinct from traditional metal‐organic frameworks (MOFs) and conventional reticular architectures, this foldamer‐based methodology provides a predictable and customizable host‐guest interaction system within a 3D topology. This innovation sets the stage for multifunctional materials that merge host‐guest interaction systems with metal‐complex properties, opening up potential applications in catalysis, sensing, and drug delivery.
This groundbreaking research uncovers an approach for crafting chiral channels in metal‐peptide networks (MPNs). The strategic integration of foldamer ligands and CuI clusters allows precise, atomic‐level modifications. The technique expedites enantiomer discrimination in mixtures and prompts adaptable molecules to adopt specific chiral forms. It promises the potential for multifunctional materials useful in catalysis, drug delivery, and sensing technologies.
Glia contribute to synapse elimination through phagocytosis in the central nervous system. Despite the important roles of this process in development and neurological disorders, the identity and ...regulation of the "eat‐me" signal that initiates glia‐mediated phagocytosis of synapses has remained incompletely understood. Here, we generated conditional knockout mice with neuronal‐specific deletion of the flippase chaperone Cdc50a, to induce stable exposure of phosphatidylserine, a well‐known "eat‐me" signal for apoptotic cells, on the neuronal outer membrane. Surprisingly, acute Cdc50a deletion in mature neurons causes preferential phosphatidylserine exposure in neuronal somas and specific loss of inhibitory post‐synapses without effects on other synapses, resulting in abnormal excitability and seizures. Ablation of microglia or the deletion of microglial phagocytic receptor Mertk prevents the loss of inhibitory post‐synapses and the seizure phenotype, indicating that microglial phagocytosis is responsible for inhibitory post‐synapse elimination. Moreover, we found that phosphatidylserine is used for microglia‐mediated pruning of inhibitory post‐synapses in normal brains, suggesting that phosphatidylserine serves as a general "eat‐me" signal for inhibitory post‐synapse elimination.
SYNOPSIS
Neuronal‐specific deletion of the flippase chaperone Cdc50a leads to exposure of phosphatidylserin on neuronal outer membranes causing specific loss of inhibitory post‐synapses and seizures. Microglial phagocytosis via the phagocytic receptor MERTK promotes inhibitory post‐synapse elimination in Cdc50a cKO brains. Inhibitory post‐synapses in normal juvenile brains also use phosphatidylserine for synapse elimination, suggesting that phosphatidylserine exposure functions as an “eat‐me” signal for microglia‐dependent inhibitory post‐synapse elimination.
Neuronal Cdc50a deletion induces rapid lethality with appearance of audiogenic seizure.
Neuronal Cdc50a deletion causes the specific loss of inhibitory post‐synapses without affecting other synapses.
Ablating microglia or deleting microglial Mertk rescues the loss of inhibitory post‐synapses and seizure behaviors in Cdc50a cKO mice.
Microglial Mertk deletion increases the number of phosphatidylserine‐exposed inhibitory post‐synapses in the wild‐type juvenile brains.
Mouse models with increased neuron‐specific exposure of an apoptotic cell‐defining phospholipid provide insight into the nature of the "eat‐me" signal and its recognition during synapse elimination.
Glutamine is an essential nutrient that regulates energy production, redox homeostasis, and signaling in cancer cells. Despite the importance of glutamine in mitochondrial metabolism, the ...mitochondrial glutamine transporter has long been unknown. Here, we show that the SLC1A5 variant plays a critical role in cancer metabolic reprogramming by transporting glutamine into mitochondria. The SLC1A5 variant has an N-terminal targeting signal for mitochondrial localization. Hypoxia-induced gene expression of the SLC1A5 variant is mediated by HIF-2α. Overexpression of the SLC1A5 variant mediates glutamine-induced ATP production and glutathione synthesis and confers gemcitabine resistance to pancreatic cancer cells. SLC1A5 variant knockdown and overexpression alter cancer cell and tumor growth, supporting an oncogenic role. This work demonstrates that the SLC1A5 variant is a mitochondrial glutamine transporter for cancer metabolic reprogramming.
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•The SLC1A5 variant is a mitochondrial glutamine transporter•The SLC1A5 variant has a mitochondrial targeting sequence•Hypoxia controls SLC1A5 variant expression through HIF-2α•The SLC1A5 variant mediates mitochondrial glutamine metabolism in cancer
Despite the importance of glutamine in cancer metabolism, the mitochondrial glutamine transporter has long been unknown. Yoo et al. show that a variant of SLC1A5 has a mitochondrial targeting signal for mitochondrial localization and is induced by HIF-2α. SLC1A5 variant knockdown suppressed cancer cell growth, supporting an oncogenic role.
SUMMARY
Proline metabolism plays a crucial role in both environmental stress responses and plant growth. However, the specific mechanism by which proline contributes to abiotic stress processes ...remains to be elucidated. In this study, we utilized atrzf1 (Arabidopsis thaliana ring zinc finger 1) as a parental line for T‐DNA tagging mutagenesis and identified a suppressor mutant of atrzf1, designated proline content alterative 31 (pca31). The pca31 mutant suppressed the insensitivity of atrzf1 to dehydration stress during early seedling growth. Using Thermal Asymmetric Interlaced‐PCR, we found that the T‐DNA of pca31 was inserted into the promoter region of the At2g22620 gene, which encodes the cell wall enzyme rhamnogalacturonan lyase 1 (RGL1). Enzymatic assays indicated that RGL1 exhibited rhamnogalacturonan lyase activity, influencing cell wall pectin composition. The decrease in RGL1 gene expression suppressed the transcriptomic perturbation of the atrzf1 mutant. Silencing of the RGL1 gene in atrzf1 resulted in a sensitive phenotype similar to pca31 under osmotic stress conditions. Treatment with mannitol, salt, hydrogen peroxide, and abscisic acid induced RGL1 expression. Furthermore, we uncovered that RGL1 plays a role in modulating root growth and vascular tissue development. Molecular, physiological, and genetic experiments revealed that the positive modulation of RGL1 during abiotic stress was linked to the AtRZF1 pathway. Taken together, these findings establish that pca31 acts as a suppressor of atrzf1 in abiotic stress responses through proline and cell wall metabolisms.
Significance Statement
RGL1 exhibits rhamnogalacturonan lyase activity, which contributes to the modulation of pectin composition, vascular tissue development, and root growth. RGL1, as a suppressor of E3 ubiquitin ligase AtRZF1, functions as a positive modulator in proline synthesis and cell wall metabolism under osmotic stress conditions.
Dysregulation of circadian rhythms is associated with metabolic dysfunction, yet it is unclear whether enhancing clock function can ameliorate metabolic disorders. In an unbiased chemical screen ...using fibroblasts expressing PER2::Luc, we identified Nobiletin (NOB), a natural polymethoxylated flavone, as a clock amplitude-enhancing small molecule. When administered to diet-induced obese (DIO) mice, NOB strongly counteracted metabolic syndrome and augmented energy expenditure and locomotor activity in a Clock gene-dependent manner. In db/db mutant mice, the clock is also required for the mitigating effects of NOB on metabolic disorders. In DIO mouse liver, NOB enhanced clock protein levels and elicited pronounced gene expression remodeling. We identified retinoid acid receptor-related orphan receptors as direct targets of NOB, revealing a pharmacological intervention that enhances circadian rhythms to combat metabolic disease via the circadian gene network.
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•High-throughput screening identified Nobiletin as a clock amplitude enhancer•Nobiletin potently protects against metabolic syndrome in a clock-dependent manner•Nobiletin remodels circadian and metabolic gene expression•Nobiletin is an agonist for the ROR nuclear receptors in the circadian oscillator
In a high-throughput chemical screen, He et al. identify the small molecule Nobiletin (NOB), a naturally occurring compound enriched in citrus peels, as a circadian clock amplitude enhancer, which protects against metabolic disease. NOB is an agonist for the ROR nuclear receptors in the circadian oscillator.
Metal–Peptide Networks
In article number 2305753, Hee‐Seung Lee and co‐workers craft enantiomeric chiral channels within metal–peptide networks (MPNs), tunable to atomic precision in size, shape, and ...function. Demonstrating chiral‐recognition capabilities, these MPNs hold promise for catalysis, sensing, and drug delivery applications.
Despite its abundance, water is not widely used as a medium for organic reactions. However, under geothermal conditions, water exhibits unique physicochemical properties, such as viscosity and a ...dielectric constant, and the ionic product become similar to those of common organic solvents. We have synthesized highly crystalline polyimide‐based covalent organic frameworks (PICs) under geomimetic hydrothermal conditions. By exploiting triphenylene‐2,3,6,7,10,11‐hexacarboxylic acid in combination with various aromatic diamines, PICs with various pore dimensions and crystallinities were synthesized. XRD, FT‐IR, and DFT calculations revealed that the solubility of the oligomeric intermediates under hydrothermal conditions affected the stacking structures of the crystalline PICs. Furthermore, the synthesized PICs demonstrate promising potential as an anode material in lithium‐ion batteries owing to its unique redox‐active properties and high surface area.
Polyimide‐based COFs were synthesized via a geomimetic hydrothermal reaction, yielding materials having various pore dimensions and crystal structures. The solubility of the oligomeric intermediates under hydrothermal conditions affected the growth mechanism and reaction pathway, which determined the 3D stacking structures of the polyimide‐based COFs.
We report a method of cancer immunotherapy using an attenuated
strain engineered to secrete
flagellin B (FlaB) in tumor tissues. Engineered FlaB-secreting bacteria effectively suppressed tumor growth ...and metastasis in mouse models and prolonged survival. By using Toll-like receptor 5 (TLR5)-negative colon cancer cell lines, we provided evidence that the FlaB-mediated tumor suppression upon bacterial colonization is associated with TLR5-mediated host reactions in the tumor microenvironment. These therapeutic effects were completely abrogated in TLR4 and MyD88 knockout mice, and partly in TLR5 knockout mice, indicating that TLR4 signaling is a requisite for tumor suppression mediated by FlaB-secreting bacteria, whereas TLR5 signaling augmented tumor-suppressive host reactions. Tumor microenvironment colonization by engineered
appeared to induce the infiltration of abundant immune cells such as monocytes/macrophages and neutrophils via TLR4 signaling. Subsequent secretion of FlaB from colonizing
resulted in phenotypic and functional activation of intratumoral macrophages with M1 phenotypes and a reciprocal reduction in M2-like suppressive activities. Together, these findings provide evidence that nonvirulent tumor-targeting bacteria releasing multiple TLR ligands can be used as cancer immunotherapeutics.
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