Soil Nitrogen Supply Exerts Largest Influence on Leaf Nitrogen in Environments with the Greatest Leaf Nitrogen Demand.

Accurately representing the relationships between nitrogen supply and photosynthesis is crucial for reliably predicting carbon-nitrogen cycle coupling in Earth System Models (ESMs). Most ESMs assume positive correlations amongst soil nitrogen supply, leaf nitrogen content, and photosynthetic capacity. However, leaf photosynthetic nitrogen demand may influence the leaf nitrogen response to soil nitrogen supply; thus, responses to nitrogen supply are expected to be the largest in environments where demand is the greatest.

Three-Dimensional SERS-Active Hydrogel Microbeads Enable Highly Sensitive Homogeneous Phase Detection of Alkaline Phosphatase in Biosystems.

Alkaline phosphatase (ALP) is a biomarker for many diseases, and monitoring its activity level is important for disease diagnosis and treatment. In this study, we used the microdroplet technology combined with an laser-induced polymerization method to prepare the Ag nanoparticle (AgNP) doped hydrogel microbeads (HMBs) with adjustable pore sizes that allow small molecules to enter while blocking large molecules. The AgNPs embedded in the hydrogel microspheres can provide SERS activity, improving the SERS signal of small molecules that diffuse to the AgNPs.

Development of a yeast-based sensor platform for evaluation of ligands recognized by the human Free Fatty Acid 2 Receptor.

Yeast-based sensors have shown great applicability for deorphanization of G protein-coupled receptors (GPCRs) and screening of ligands targeting these. A GPCR of great interest is free fatty acid 2 receptor (FFA2R), for which short-chain fatty acids such as propionate and acetate are agonists. FFA2R regulates a wide array of downstream receptor signaling pathways in both adipose tissue and immune cells and has been recognized as a promising therapeutic target, having been implicated in several metabolic and inflammatory diseases.

Community assembly of gut microbiomes in yolk sac fry of Atlantic salmon: host genetics, environmental microbiomes, and ecological processes.

In this study, we investigated the influence of host genetics and environmental microbiomes on the early gut microbiome of Atlantic salmon. We aimed at rearing the fish in either r- or K-selected environments, where the r-selected environment would be expected to be dominated by fast-growing opportunistic bacteria and thus represent more detrimental microbial environment than the K-selected water. Eggs from both wild and aquaculture strains of Atlantic salmon were hatched under germ-free conditions.

Social isolation during adolescence differentially affects spatial learning in adult male and female mice.

Social isolation is a risk factor for cognitive impairment. Adolescents may be particularly vulnerable to these effects, because they are in a critical period of development marked by significant physical, hormonal, and social changes. However, it is unclear if the effects of social isolation on learning and memory are similar in both sexes or if they persist into adulthood after a period of recovery.

Large donor CRISPR for whole-CDS replacement of cell adhesion molecule LRRTM2.

The cell adhesion molecule Leucine-Rich Repeat Transmembrane neuronal protein 2 (LRRTM2) is crucial for synapse development and function. However, our understanding of its endogenous trafficking has been limited due to difficulties in manipulating its coding sequence (CDS) using standard genome editing techniques. Instead, we replaced the entire LRRTM2 CDS by adapting a two-guide CRISPR knock-in method, enabling complete control of LRRTM2.

CRISPR challenges in clinical developments.

CRISPR-Cas (clustered regularly interspaced short palindromic repeats and associated proteins) is a novel genome editing technology with potential applications in treating diseases. Currently, its use in humans is restricted to clinical trials, although its growth rate is significant, and some have received initial FDA approval. It is crucial to examine and address the challenges for this technology to be implemented in clinical settings.

Recent progress in CRISPR-Cas-system for neurological disorders.

Different neurological diseases including, Parkinson's, Alzheimer's, and Huntington's diseases extant momentous global disease burdens, affecting millions of lives for imposing a heavy disease burden on the healthcare systems. Despite various treatment strategies aimed at alleviating symptoms, treatments remain elusive and ineffective due to the disease's complexity. However, recent advancements in gene therapy via the CRISPR-Cas system offer ground-breaking and targeted treatment options.

Current progress in CRISPR-Cas systems for rare diseases.

The groundbreaking CRISPR-Cas gene editing method permits exact genetic code alteration. The "CRISPR" DNA protects bacteria from viruses. CRISPR-Cas utilizes a guide RNA to steer the Cas enzyme to the genome's gene editing target.

Ex vivo assessment of human neutrophil motility and migration.

Neutrophils are pivotal in orchestrating tumor-induced systemic inflammation and are increasingly recognized for their critical involvement in both the initiation and progression of cancer. A fundamental facet of neutrophil biology is their migratory capacity, which enables them to extravasate and infiltrate tumors in other tissues, where they carry out essential effector functions. Unraveling the intricate mechanisms of neutrophil motility and migration is crucial for comprehending immune responses and inflammatory processes, shedding light on their substantial contribution to cancer progression.

Simplified acid extraction and quantification of histones in human tumor cells.

Histones are essential nuclear proteins that package eukaryotic DNA into chromosomes, play a vital role in gene regulation, DNA replication, DNA repair and chromosome condensation. Understanding histone modifications is crucial for grasping biological and disease-related processes. Specific alterations in histone modifications serve as sensitive and selective biomarkers for conditions like cancer, impacting both tumor and immune cells and affecting their interactions.

Advances in the understanding and therapeutic manipulation of cancer immune responsiveness: a Society for Immunotherapy of Cancer (SITC) review.

Cancer immunotherapy-including immune checkpoint inhibition (ICI) and adoptive cell therapy (ACT)-has become a standard, potentially curative treatment for a subset of advanced solid and liquid tumors. However, most patients with cancer do not benefit from the rapidly evolving improvements in the understanding of principal mechanisms determining cancer immune responsiveness (CIR); including patient-specific genetically determined and acquired factors, as well as intrinsic cancer cell biology. Though CIR is multifactorial, fundamental concepts are emerging that should be considered for the design of novel therapeutic strategies and related clinical studies.

Randle Cycle in Practice: a student exercise to teach glucose- and fatty acid metabolism in fasted, fed and exercised states.

Here we describe an approach and overall concept on how to train undergraduate university students to understand basic regulation and integration of glucose and fatty acid metabolism in response to fasting, intake of carbohydrates and aerobic exercise. During lectures and both theoretical and practical sessions, the students read, analyse, and discuss the fundamentals of Randle cycle. They focus on how metabolism is regulated in adipose tissue, skeletal muscle, and liver at a molecular level under various metabolic conditions.

Intracellular Pocket Conformations Determine Signaling Efficacy through the μ Opioid Receptor.

It has been challenging to determine how a ligand that binds to a receptor activates downstream signaling pathways and to predict the strength of signaling. The challenge is compounded by functional selectivity, in which a single ligand binding to a single receptor can activate multiple signaling pathways at different levels. Spectroscopic studies show that in the largest class of cell surface receptors, 7 transmembrane receptors (7TMRs), activation is associated with ligand-induced shifts in the equilibria of intracellular pocket conformations in the absence of transducer proteins.

Novel Quinazoline Derivatives Inhibit Splicing of Fungal Group II Introns.

We report the discovery of small molecules that target the RNA tertiary structure of self-splicing group II introns and display potent antifungal activity against yeasts, including the major public health threat . High-throughput screening efforts against a yeast group II intron resulted in an inhibitor class which was then synthetically optimized for enhanced inhibitory activity and antifungal efficacy. The most highly refined compounds in this series display strong, gene-specific antifungal activity against .

TGR5 attenuates DOCA-salt hypertension through regulating histone H3K4 methylation of ENaC in the kidney.

Epithelial sodium channel (ENaC), located in the collecting duct principal cells of the kidney, is responsible for the reabsorption of sodium and plays a critical role in the regulation of extracellular fluid volume and consequently blood pressure. The G protein-coupled bile acid receptor (TGR5) is a membrane receptor mediating effects of bile acid and is implicated in kidney diseases. The current study aims to investigate whether TGR5 activation in the kidney regulated ENaC expression and potential mechanism.

Ketogenesis nutritionally supports brain during bacterial infection in Drosophila.

Mounting an immune response is a nutritionally demanding process that requires the systemic redistribution of energy stores towards the immune system. This is facilitated by cytokine-induced insulin resistance, which simultaneously promotes the mobilization of lipids and carbohydrates while limiting their consumption in immune-unrelated processes, such as development, growth, and reproduction. However, this adaptation also restricts the availability of nutrients to vital organs, which must then be sustained by alternative fuels.

Enhanced thermogenesis in PAS Kinase-deficient male mice.

PAS domain-containing serine/threonine-protein kinase (PASK) is a nutrient and energy sensor regulated by fasting/refeeding conditions in hypothalamic areas involved in controlling energy balance. In this sense, PASK plays a role in coordinating the activation/inactivation of AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) in response to fasting. PASK deficiency protects against the development of diet-induced obesity.

PSMC2 promotes resistance against temozolomide in glioblastoma via suppressing JNK-mediated autophagic cell death.

Temozolomide is universally used to treat glioblastoma due to its unique ability to cross the blood-brain barrier and inhibit tumor growth through DNA alkylation. However, over time, the inevitable emergence of resistance to temozolomide impedes successful treatment of this cancer. As a result, there is an urgent need to identify new therapeutic targets to improve treatment outcomes for this malignancy.

Gold(I) N-heterocyclic carbene complexes show strong proapoptotic, antioxidant and anti-inflammatory effects in A2780 and endothelial cells.

A series of eight gold(I) N-heterocyclic carbene (NHC) complexes [Au(IMes)(HLn)] based on 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes) and 7-azaindole derivatives (HLn), where n = 1-8 for HL1 = 5-flouro-7-azaindole, HL2 = 5-bromo-7-azaindole, HL3 = 3-chloro-7-azaindole, HL4 = 3-iodo-7-azaindole, HL5 = 5-bromo-3-chloro-7-azaindole, HL6 = 5-bromo-3-iodo-7-azaindole, HL7 = 4-chloro-2-methyl-7-azaindole and HL8 = 7-azaindole, was prepared, characterised and studied for their in vitro anti-cancer and anti-inflammatory effects. The complexes showed significant cytotoxicity on human ovarian cancer cell lines (A2780, IC ≈ 8-19 μM and A2780R, IC ≈ 8-19 μM) and lowered toxicity in normal HaCat and MRC-5 cells. Cellular effects of the selected complexes 1 and 7 were evaluated in A2780 cells using flow cytometry.

Bio-fabrication of chitosan-stabilized magnesium oxide nanomaterials: Investigation of photocatalytic, in vitro cytotoxicity activities and apoptosis in oral squamous carcinoma cells.

A bio-fabrication approach is a novel way to develop chitosan-stabilized magnesium oxide nanomaterials (cMgO-NMs). The process involves utilizing polymeric chitosan as the reducing and stabilizing agent. The characteristics of the developed cMgO-NMs were determined using various spectroscopical techniques.

Antioxidant and anti-aging activities of Acanthopanax senticosus polysaccharide CQ-1 in nematode Caenorhabditis elegans.

Acanthopanax senticosus is a typical food medicine homology in China. The antioxidant and anti-aging activities of A. senticosus polysaccharides, especially the purified polysaccharide, have not been thoroughly investigated.

Integrated GelMA and liposome composite hydrogel with effective coupling of angiogenesis and osteogenesis for promoting bone regeneration.

In clinical scenarios, bone defects stemming from trauma, infections, degenerative diseases, or hereditary conditions necessitate considerable bone grafts. Researchers ardently focus on creating diverse biomaterials to expedite and enhance these intricate restorative processes. These biomaterials play a pivotal role in aiding osteogenesis and angiogenesis factors for reconstructing stable, fully developed bone tissue.