Glutathione Synthesis via the Cystine/Glutamate Transporter Promotes the Formation of Tertiary Lymphoid Structures in the Kidney.

Background: Tertiary lymphoid structure, an ectopic lymphoid tissue induced under chronic inflammation, develops in various kidney diseases and is associated with poor prognosis. The immune system requires metabolic resources to support immune function and lymphocyte proliferation. Hence, dramatic metabolic alterations presumably occur during the formation of tertiary lymphoid structure.

Senescence-associated lysosomal dysfunction impairs cystine deprivation-induced lipid peroxidation and ferroptosis.

Senescent cells, characterized by irreversible cell cycle arrest and inflammatory factor secretion, promote various age-related pathologies. Senescent cells exhibit resistance to ferroptosis, a form of iron-dependent cell death; however, the underlying mechanisms remain unclear. Here, we discovered that lysosomal acidity was crucial for lipid peroxidation and ferroptosis induction by cystine deprivation.

Decreased non-neurogenic acetylcholine in bone marrow triggers age-related defective stem/progenitor cell homing.

Age-related decline in the ability of bone marrow (BM) to recruit transplanted hematopoietic stem and progenitor cells (HSPCs) limits the potential of HSPC-based medicine. Using in vivo imaging and manipulation combined with integrative metabolomic analyses, we show that, with aging, degradation of non-neurogenic acetylcholine disrupts the local Chrm5-eNOS-nitric oxide signaling, reducing arterial dilation and decreasing both BM blood flow and sinusoidal wall shear stress. Consequently, aging BM microenvironment impairs transendothelial migration of transplanted HSPCs, and their BM homing efficiency is reduced, mediated by decreased activation of Piezo1.

Whole Slide Imaging-Free Supporting Tool for Cytotechnologists in Cervical Cytology.

Cervical cytology is a crucial method for detecting cancerous and precancerous lesions. However, traditional workflows rely heavily on manual microscopic observations by cytotechnologists, making the process time-consuming and labor-intensive. Although several artificial intelligence (AI)-assisted cytology systems have been developed, most approaches require whole slide images, which entails costly scanning equipment, extensive data storage, and additional processing time.

Hormetic elevation of taurine restrains inflammaging by deactivating the NLRP3 inflammasome.

Taurine, the most abundant sulfonic amino acid in humans is largely obtained from diets rich in animal proteins. However, taurine is dietary non-essential because it can be synthesized from cysteine by activation of transsulfuration pathway (TSP) when food consumption is low or if the diet is predominantly plant based. The decline of taurine was proposed as the driver of aging through an undefined mechanism.

Cysteine depletion triggers adipose tissue thermogenesis and weight loss.

Caloric restriction and methionine restriction-driven enhanced lifespan and healthspan induces 'browning' of white adipose tissue, a metabolic response that increases heat production to defend core body temperature. However, how specific dietary amino acids control adipose thermogenesis is unknown. Here, we identified that weight loss induced by caloric restriction in humans reduces thiol-containing sulfur amino acid cysteine in white adipose tissue.

Integrated hepatic ferroptosis gene signature dictates pathogenic features of ferroptosis.

Background: Ferroptosis, a distinctive form of cell death induced by iron-dependent lipid peroxidation, is implicated in various biological processes, including liver diseases. Establishing an iron overload-induced ferroptosis model and identifying hepatic gene signatures associated with ferroptosis are crucial for understanding its role in liver pathogenesis.

Methods: F-box and leucine-rich repeat protein 5 (FBXL5) is a substrate-recognition component of the SCF E3 ligase complex that restricts intracellular iron levels.

Prediction of postoperative delirium by blood metabolome analysis.

No established blood markers can preoperatively predict postoperative delirium. Blood concentrations of amino acid catabolites and dipeptides, including those secreted extracellularly during T-lymphocyte activation, were investigated as predictors of postoperative delirium using metabolomic analyses to ascertain whether preoperative blood metabolites could predict postoperative delirium. Eighteen and 24 participants were included in the delirium and non-delirium groups, respectively.

Maternal progesterone and adipose mPRε in pregnancy regulate the embryonic nutritional state.

Sex steroid hormones such as progesterone play a pivotal role in reproductive functions and maintaining pregnancy; however, the impact of progesterone on the interaction between mother and embryo is unclear. Here, we demonstrate that the relationship between maternal progesterone and membrane progesterone receptor epsilon (mPRε) in adipose tissue regulates embryonic nutritional environment and growth after birth in mice. The activation of adipose mPRε by increased progesterone during pregnancy enhances maternal insulin resistance via prostaglandin production, efficiently providing glucose to embryos.

Ovarian tachykinin signaling system induces the growth of secondary follicles during the gonadotropin-independent process.

Mammalian follicle growth development is mainly regulated by the hypothalamus-pituitary-gonadal axis after puberty. Although pituitary hormones, gonadotropins, are involved in hypothalamus-pituitary-gonadal axis signaling, they are not responsible for the growth of early stage follicles, namely, primordial follicles, primary follicles, and secondary follicles, in both sexually immature and mature individuals. Unlike those of gonadotropin-dependent follicle growth, the specific regulatory factors of gonadotropin-independent follicle growth have yet to be identified.

Branched-chain amino acids and specific phosphatidylinositols are plasma metabolite pairs associated with menstrual pain severity.

Menstrual pain affects women's quality of life and productivity, yet objective molecular markers for its severity have not been established owing to the variability in blood levels and chemical properties of potential markers such as plasma steroid hormones, lipid mediators, and hydrophilic metabolites. To address this, we conducted a metabolomics study using five analytical methods to identify biomarkers that differentiate menstrual pain severity. This study included 20 women, divided into mild (N = 12) and severe (N = 8) pain groups based on their numerical pain rating scale.

Creatinine production rate is an integrative indicator to monitor muscle status in critically ill patients.

Background: Both quantitative and qualitative aspects of muscle status significantly impact clinical outcomes in critically ill patients. Comprehensive monitoring of baseline muscle status and its changes is crucial for risk stratification and management optimization. However, repeatable and accessible indicators are lacking.

Single-Molecule Oxidoreductase Activity Analysis for Activity-Based Diagnosis Based on Proteoform Alterations.

We developed a single-molecule enzyme activity assay platform for NAD(P)-dependent oxidoreductases, leveraging a new NAD(P)H-responsive fluorogenic probe optimized for microdevice-based fluorometric detection. This platform enabled the detection of enzyme activities in blood and cerebrospinal fluid (CSF), including lactate dehydrogenase, glucose-6-phosphate dehydrogenase, and hexokinases. We demonstrate its potential for activity-based diagnosis by detecting altered populations of enzyme activity species in blood and CSF from liver damage in brain tumor patients.

Redox-dependent purine degradation triggers postnatal loss of cardiac regeneration potential.

Postnatal cardiomyocyte cell cycle withdrawal is a critical step wherein the mammalian heart loses regenerative potential after birth. Here, we conducted interspecies multi-omic comparisons between the mouse heart and that of the opossum, which have different postnatal time-windows for cardiomyocyte cell cycle withdrawal. Xanthine metabolism was activated in both postnatal hearts in parallel with cardiomyocyte cell cycle arrest.