Glucocorticoid-induced adrenal insufficiency and glucocorticoid withdrawal syndrome: Two sides of the same coin.

Diseases of the adrenal glands can lead to primary adrenal insufficiency, and suppression of the hypothalamic-pituitary-adrenal axis can cause secondary adrenal insufficiency (adrenal suppression). The most common cause of adrenal suppression is exogenous steroids, a condition recently termed glucocorticoid-induced adrenal insufficiency (GIAI). Similarly, weaning from high doses of glucocorticoids or giving insufficient glucocorticoid replacement after curative surgery for endogenous hypercortisolism (Cushing syndrome) can lead to glucocorticoid withdrawal syndrome, which overlaps with GIAI.

Cholesterol Metabolism in Neurodegenerative Diseases.

Significance: Cholesterol plays a crucial role in the brain, where it is highly concentrated and tightly regulated to support normal brain functions. It serves as a vital component of cell membranes, ensuring their integrity, and acts as a key regulator of various brain processes. Dysregulation of cholesterol metabolism in the brain has been linked to impaired brain function and the onset of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease, and Huntington's disease. Recent Advances: A significant advancement has been the identification of astrocyte-derived apoliprotein E as a key regulator of de novo cholesterol biosynthesis in neurons, providing insights into how extracellular signals influence neuronal cholesterol levels. In addition, the development of antibody-based therapies, particularly for AD, presents promising opportunities for therapeutic interventions. Critical Issues: Despite significant research, the association between cholesterol and neurodegenerative diseases remains inconclusive. It is crucial to distinguish between plasma cholesterol and brain cholesterol, as these pools are relatively independent. This differentiation should be considered when evaluating statin-based treatment approaches. Furthermore, assessing not only the total cholesterol content in the brain but also its distribution among different types of brain cells is essential. Future Direction: Establishing a causal link between changes in brain/plasma cholesterol levels and the onset of brain dysfunction/neurodegenerative diseases remains a key objective. In addition, conducting cell-specific analyses of cholesterol homeostasis in various types of brain cells under pathological conditions will enhance our understanding of cholesterol metabolism in neurodegenerative diseases. Manipulating cholesterol levels to restore homeostasis may represent a novel approach for alleviating neurological symptoms.

Sulfide-carbonate-mineralized functional bacterial consortium for cadmium removal in flue gas.

Sulfide-carbonate-mineralized functional bacterial consortium was constructed for flue gas cadmium biomineralization. A membrane biofilm reactor (MBfR) using the bacterial consortium containing sulfate reducing bacteria (SRB) and denitrifying bacteria (DNB) was investigated for flue gas cadmium (Cd) removal. Cadmium removal efficiency achieved 90%. The bacterial consortium containing Citrobacter, Desulfocurvus and Stappia were dominated for cadmium resistance-nitrate-sulfate reduction. Under flue gas cadmium stress, ten cadmium resistance genes (czcA, czcB, czcC, czcD, cadA, cadB, cadC, cueR, copZ, zntA), and seven genes related to sulfate reduction, increased in abundance; whereas others, nine genes related to denitrification, decreased, indicating that cadmium stress was advantageous to sulfate reduction in the competition with denitrification. A bacterial consortium could capable of simultaneously cadmium resistance, sulfate reduction and denitrification. Microbial induced carbonate precipitation (MICP) and biological adsorption process would gradually yield to sulfide-mineralized process. Flue gas cadmium could transform to Cd-EPS, cadmium carbonate (CdCO3) and cadmium sulfide (CdS) bioprecipitate. The functional bacterial consortium was an efficient and eco-friendly bifunctional bacterial consortium for sulfide-carbonate-mineralized of cadmium. This provides a green and low-carbon advanced treatment technology using sulfide-carbonate-mineralized functional bacterial consortium for the removal of cadmium or other hazardous heavy metal contaminants in flue gas.

Aging-induced tRNAGlu-derived fragment impairs glutamate biosynthesis by targeting mitochondrial translation-dependent cristae organization.

Mitochondrial cristae, infoldings of the mitochondrial inner membrane, undergo aberrant changes in their architecture with age. However, the underlying molecular mechanisms and their contribution to brain aging are largely elusive. Here, we observe an age-dependent accumulation of Glu-5'tsRNA-CTC, a transfer-RNA-derived small RNA (tsRNA), derived from nuclear-encoded tRNAGlu in the mitochondria of glutaminergic neurons. Mitochondrial Glu-5'tsRNA-CTC disrupts the binding of mt-tRNALeu and leucyl-tRNA synthetase2 (LaRs2), impairing mt-tRNALeu aminoacylation and mitochondria-encoded protein translation. Mitochondrial translation defects disrupt cristae organization, leading to damaged glutaminase (GLS)-dependent glutamate formation and reduced synaptosomal glutamate levels. Moreover, reduction of Glu-5'tsRNA-CTC protects aged brains from age-related defects in mitochondrial cristae organization, glutamate metabolism, synaptic structures, and memory. Thus, beyond illustrating a physiological role for normal mitochondrial cristae ultrastructure in maintaining glutamate levels, our study defines a pathological role for tsRNAs in brain aging and age-related memory decline.

Clinical and imaging presentations are associated with function in incidental adrenocortical adenomas: a retrospective cohort study.

OBJECTIVE: The aim of this study is to assess whether clinical and imaging characteristics are associated with the hormonal subtype, growth, and adrenalectomy for incidental adrenal cortical adenomas (ACAs). DESIGN: This is a single-center cohort study. METHODS: Consecutive adult patients with incidental ACA were diagnosed between 2000 and 2016. RESULTS: Of the 1516 patients with incidental ACA (median age 59 years, 62% women), 699 (46%) had nonfunctioning adenomas (NFAs), 482 (31%) had mild autonomous cortisol secretion (MACS), 62 (4%) had primary aldosteronism (PA), 39 (3%) had Cushing syndrome, 18 (1%) had PA and MACS, and 226 (15%) had incomplete work-up. Age, sex, tumor size, and tumor laterality, but not unenhanced computed tomography Hounsfield units (HU), were associated with hormonal subtypes. In a multivariable analysis, ≥1 cm growth was associated with younger age (odds ratio [OR] = 0.8 per 5-year increase, P = .0047) and longer imaging follow-up (OR = 1.2 per year, P < .0001). Adrenalectomy was performed in 355 (23%) patients, including 38% of MACS and 15% of NFA. Adrenalectomy for NFA and MACS was more common in younger patients (OR = 0.79 per 5-year increase, P = .002), larger initial tumor size (OR = 2.3 per 1 cm increase, P < .0001), ≥1 cm growth (OR = 15.3, P < .0001), and higher postdexamethasone cortisol (OR = 6.6 for >5 vs <1.8 µg/dL, P = .002). CONCLUSIONS: Age, sex, tumor size, and laterality were associated with ACA hormonal subtype and can guide diagnosis and management. Tumor growth was more common with younger age and longer follow-up. Unenhanced HU did not predict hormonal subtype or growth. Adrenalectomy for MACS and NFA was mainly performed in younger patients with larger tumor size, growth, and elevated postdexamethasone cortisol.