Single-Cell RNA Sequencing and Its Applications in Pituitary Research.

BACKGROUND: Mounting evidence underscores the significance of cellular diversity within the endocrine system and the intricate interplay between different cell types and tissues, essential for preserving physiological balance and influencing disease trajectories. The pituitary gland, a central player in the endocrine orchestra, exemplifies this complexity with its assortment of hormone-secreting and nonsecreting cells. SUMMARY: The pituitary gland houses several types of cells responsible for hormone production, alongside nonsecretory cells like fibroblasts and endothelial cells, each playing a crucial role in the gland's function and regulatory mechanisms. Despite the acknowledged importance of these cellular interactions, the detailed mechanisms by which they contribute to pituitary gland physiology and pathology remain largely uncharted. The last decade has seen the emergence of groundbreaking technologies such as single-cell RNA sequencing, offering unprecedented insights into cellular heterogeneity and interactions. However, the application of this advanced tool in exploring the pituitary gland's complexities has been scant. This review provides an overview of this methodology, highlighting its strengths and limitations, and discusses future possibilities for employing it to deepen our understanding of the pituitary gland and its dysfunction in disease states. KEY MESSAGE: Single-cell RNA sequencing technology offers an unprecedented means to study the heterogeneity and interactions of pituitary cells, though its application has been limited thus far. Further utilization of this tool will help uncover the complex physiological and pathological mechanisms of the pituitary, advancing research and treatment of pituitary diseases.

Temozolomide Therapy in Management of Refractory Pituitary Adenomas: A Case Series of 39 Patients.

OBJECTIVE: The management of refractory pituitary adenomas (RPA) presents significant challenges. This study aimed to evaluate the long-term treatment outcomes of patients with RPA managed with temozolomide (TMZ) and to identify potential biomarkers for predicting TMZ treatment response. METHODS: This retrospective case series included patients with RPA who underwent transsphenoidal surgery (TSS) or craniotomy at a comprehensive medical center in China between January 2014 and December 2021. RESULTS: Thirty-nine patients with RPA (median age 42 years; 23 males (59%)) were treated with TMZ for a median of 9 cycles. The median follow-up was 34.4 months. Complete response (CR) was observed in 2 patients, partial response (PR) in 11 patients, stable disease (SD) in 9, progressive disease (PD) in 11, and death in 6 patients. MGMT (O6-methylguanine DNA methyltransferase) levels were significantly lower in patients with CR, PR, or SD compared to those with PD or mortality, with mean values of 24.2% and 58.1, respectively. MSH6 (MutS homologs 6) levels were significantly higher in patients with CR, PR, or SD compared to those with PD or mortality, with mean values of 64.2% and 36.9%, respectively. Patients who received concomitant TMZ and external beam radiotherapy showed a significant tumor size reduction of 178,837mm3 (p<0.001) compared to those treated with TMZ alone. CONCLUSIONS: TMZ demonstrates promising efficacy in eliciting tumor responses in patients with PRA. MGMT and MSH6 have emerged as potential biomarkers for predicting treatment response. Furthermore, radiation with concurrent TMZ may significantly improve outcomes in patients with RPA.

Green Solvent Cleaning Removes Irrecoverable Foulants from End-of-Life Membranes in Membrane Bioreactors: Efficacy and Mechanisms.

Removal of irrecoverable foulants, which cannot be removed by conventional chemical cleaning, from end-of-life (EOL) membranes remains a substantial challenge due to the strong interaction between the foulants and membrane matrix. Herein, we developed a green solvent cleaning strategy based on Hansen solubility parameters to achieve the removal of irrecoverable foulants from the EOL polyvinylidene fluoride (PVDF) membranes serving for 6 years in a large-scale membrane bioreactor (MBR). We selected methyl-5-(dimethylamino)-2-methyl-5-oxopentanoate (MDMO) as the green solvent due to its strong interaction with the PVDF material, which might enable the substitution of binding sites of irrecoverable foulants. After the MDMO cleaning, the water permeance of the EOL membrane recovered from 47.6 ± 4.7 to 390.9 ± 8.2 L m-2 h-1 bar-1 (with a flux recovery ratio of ∼100%), with its rejection ability and stability maintained. The main components of irrecoverable fouling were humic acid-like substances revealed by spectroscopic characterization. Molecular dynamic simulation further elucidated the cleaning mechanisms: the strong interaction of MDMO-PVDF enabled substitution of binding sites of irrecoverable foulants by MDMO, followed by desorption of the irrecoverable foulants from PVDF and diffusion of the irrecoverable foulants into the bulk phase of MDMO. Evaluation in a lab-scale MBR treating real municipal wastewater verified the reusability of green solvent cleaned-EOL membranes. This study provides a novel, effective, and green cleaning strategy to remove irrecoverable foulants and prolong the service life of membranes in MBRs, facilitating sustainable wastewater treatment using membrane-based processes.

Removal of tetracycline-resistant Escherichia coli and its genes through ultrasound treatment combined with ultraviolet light emitting diodes.

Antibiotic resistance has gained increasing attention worldwide, and wastewater treatment plants have been regarded as hotspots for antibiotic-resistant bacteria and antibiotic-resistant genes (ARGs). In this study, we evaluated the removal of tetracycline-resistant Escherichia coli and its related genes through ultrasound (US) treatment with different input levels of US-specific energy combined with ultraviolet light emitting diodes (UV-LEDs). Simultaneous US with UV-LEDs effectively eliminated tetracycline-resistant E. coli with the normal suggested UV-LEDs dosage (below 30 mJ/cm2). The removal efficiency increased with the addition of US (specific input energy of 8-16 kJ/L), and simultaneous US treatment with UV-LEDs was relatively more effective than US pretreatment. Analyses of cell damage by K+ leakage and flow cytometry showed that the cell wall kept its integrity during the applied treatment conditions. Consequently, the removal efficiencies of 16 S rRNA, tet M, and tet Q were unsatisfactory because less than 1 log reduction was achieved. Increasing the US energy remarkably damaged the cell wall and potentially promoted the reaction. The removal of ARGs increased four times when using US-specific input energy at 330 kJ/L with 5 mJ/cm2 compared with UV-LEDs alone. The US treatment combined with UV-LEDs is a novel process that does not require chemicals. Results of this research can provide theoretical support for the removal of ARGs.

Cross-sectional associations between multisensory impairment and brain volumes in older adults: Baltimore Longitudinal Study of Aging.

Sensory impairment and brain atrophy is common among older adults, increasing the risk of dementia. Yet, the degree to which multiple co-occurring sensory impairments (MSI across vision, proprioception, vestibular function, olfactory, and hearing) are associated with brain morphometry remain unexplored. Data were from 208 cognitively unimpaired participants (mean age 72 ± 10 years; 59% women) enrolled in the Baltimore Longitudinal Study of Aging. Multiple linear regression models were used to estimate cross-sectional associations between MSI and regional brain imaging volumes. For each additional sensory impairment, there were associated lower orbitofrontal gyrus and entorhinal cortex volumes but higher caudate and putamen volumes. Participants with MSI had lower mean volumes in the superior frontal gyrus, orbitofrontal gyrus, superior parietal lobe, and precuneus compared to participants with < 2 impairments. While MSI was largely associated with lower brain volumes, our results suggest the possibility that MSI was associated with higher basal ganglia volumes. Longitudinal analyses are needed to evaluate the temporality and directionality of these associations.

Biofouling suppresses effluent toxicity in an electrochemical filtration system for remediation of sulfanilic acid-contaminated water.

Electrochemical filtration system (EFS) has received broad interest due to its high efficiency for organic contaminants removal. However, the porous nature of electrodes and flow-through operation mode make it susceptible to potential fouling. In this work, we systematically investigated the impacts of biofouling on sulfanilic acid (SA) removal and effluent toxicity in an EFS. Results showed that the degradation efficiency of SA slightly deteriorated from 92.3% to 81.1% at 4.0 V due to the electrode fouling. Surprisingly, after the occurrence of fouling, the toxicity (in terms of luminescent bacteria inhibition) of the EFS effluent decreased from 72.3% to 40.2%, and cytotoxicity assay exhibited similar tendency. Scanning electron microscopy and confocal laser scanning microscopy analyses revealed that biofouling occurred on the porous cathode, and live microorganisms were the dominant contributors, which are expected to play an important role in toxicity suppression. The relative abundance of Flavobacterium genus, related to the degradation of p-nitrophenol (an aromatic intermediate product of SA), increased on the membrane cathode after fouling. The analysis of degradation pathway confirmed the synergetic effects of electrochemical oxidation and biodegradation in removal of SA and its intermediate products in a bio-fouled EFS, accounting for the decrease of the effluent toxicity. Results of our study, for the first time, highlight the critical role of biofouling in detoxication using EFS for the treatment of contaminated water.

Efficacy of a novel electrochemical membrane-aerated biofilm reactor for removal of antibiotics from micro-polluted surface water and suppression of antibiotic resistance genes.

An electrochemical membrane-aerated biofilm reactor (EMABR) was developed for removing sulfamethoxazole (SMX) and trimethoprim (TMP) from contaminated water. The exertion of electric field greatly enhanced the degradation of SMX and TMP in the EMABR (~60%) compared to membrane-aerated biofilm reactor (MABR, < 10%), due to the synergistic effects of the electro-oxidation (the generation of reactive oxygen species) and biological degradation. Microbial community analyses demonstrated that the EMABR enriched the genus of Xanthobacter, which was potentially capable of degrading aromatic intermediates. Moreover, the EMABR had a lower relative abundance of antibiotic resistance genes (ARGs) (0.23) compared to the MABR (0.56), suggesting the suppression of ARGs in the EMABR. Further, the SMX and TMP degradation pathways were proposed based on the detection of key intermediate products. This study demonstrated the potential of EMABR as an effective technology for removing antibiotics from micro-polluted surface water and suppressing the development of ARGs.