Regulating Triplet Excitons of Organic Luminophores for Promoted Bioimaging.

Afterglow materials with organic room temperature phosphorescence (RTP) or thermally activated delayed fluorescence (TADF) exhibit significant potential in biological imaging due to their long lifetime. By utilizing time-resolved technology, interference from biological tissue fluorescence can be mitigated, enabling high signal-- to-background ratio imaging. Despite the continued emergence of individual reports on RTP or TADF in recent years, comprehensive reviews addressing these two materials are rare. Therefore, this review aims to provide a comprehensive overview of several typical molecular designs for organic RTP and TADF materials. It also explores the primary methods through which triplet excitons resist quenching by water and oxygen. Furthermore, we analyze the principal challenges faced by afterglow materials and discuss key directions for future research with the hope of inspiring developments in afterglow imaging.

Synchronous stabilization of Pb, Zn, Cd, and As in lead smelting slag by industrial solid waste.

In order to prevent heavy metal (HM) pollution from lead smelting slag (LSS) to the surrounding environment, this work investigated the feasibility, influencing factors, and mechanisms of using industrial solid waste such as fly ash (FA), oil sludge pyrolysis residue (PR), and steel slag (SS) as remediation amendments. The results demonstrated that the stabilization process was influenced by the material dosage, water content, and LSS particle size. Compared to single materials, the combination amendment PR2FA1 (with a mass ratio of PR to FA as 2:1) exhibited the best stabilization effect, simultaneously reducing the leaching concentrations of As, Zn, Cd, and Pb in LSS to 0.032, 0.034, 0.002, and 0.014 mg/L, respectively. The pH value of the leachate remained between 8 and 9, which met the requirements of surface water quality class IV (GB3838-2002). Through morphological analysis, microscopic characterization, and simulated solution adsorption experiments, it was determined that the stabilization process of HMs was controlled by various mechanisms, including electrostatic attraction, physical adsorption, ion exchange, and chemical precipitation. PR2FA1 had more active components, and its fine-porous structure provided more active sites, resulting in good stabilization performance for As, Zn, Cd, and Pb. Furthermore, cost analysis showed that PR2FA1, as an environmentally friendly material, could generate profits of 157.2 ¥/ton. In conclusion, the prepared PR2FA1 not only addressed the HMs pollution from lead smelting slag to the surrounding environment but also achieved the safe and resourceful disposal of hazardous waste-oil sludge. Its excellent performance in stabilizing HMs and cost-effectiveness suggested promising commercial applications.

Advanced Peptide Nanomedicines for Bladder Cancer Theranostics.

Cancer is still a global public health problem. Although remarkable success has been achieved in cancer diagnosis and treatment, the high recurrence and mortality rates remain severely threatening to human lives and health. In recent years, peptide nanomedicines with precise selectivity and high biocompatibility have attracted intense attention in biomedical applications. In particular, there has been a significant increase in the exploration of peptides and their derivatives for malignant tumor therapy and diagnosis. Herein, we review the applications of peptides and their derivatives in the diagnosis and treatment of bladder cancer, providing new insights for the design and development of novel peptide nanomedicines for the treatment of bladder cancer in the future.

[6]-Gingerol Ameliorates Cisplatin-Induced Pica by Regulating the TPH/MAO-A/SERT/5-HT/5-HT3 Receptor System in Rats.

PURPOSE: [6]-gingerol is a bioactive compound extracted from ginger, a traditional anti-emetic herb in Chinese medicine. Previous studies have demonstrated that [6]-gingerol can ameliorate chemotherapy-induced pica in rats, although the underlying mechanism has not been elucidated. This study is designed to investigate [6]-gingerol's antiemetic mechanism focusing on the 5-hydroxytryptamine (serotonin, 5-HT) system by evaluating the synthesis, metabolism and reuptake of 5-HT, as well as the mechanism of 5-hydroxytryptamine type 3 receptor (5-HT3 receptor), in a cisplatin-induced pica model of rats. METHODS: Rats were randomly divided into control group (vehicle + saline, Con), [6]-gingerol control group (50 mg/kg [6]-gingerol + saline, G-con), ondansetron control group (2.6 mg/kg ondansetron + saline, O-con), cisplatin model group (vehicle + cisplatin, Model), ondansetron-treated group (2.6 mg/kg ondansetron + cisplatin, O-treated), high dosage of [6]-gingerol-treated group (100 mg/kg [6]-gingerol + cisplatin, GH-treated), and low dosage of [6]-gingerol-treated group (50 mg/kg [6]-gingerol + cisplatin, GL-treated). The rats were administered with [6]-gingerol, ondansetron, and vehicle (3% Tween-80) by gavage twice (7:00 AM and 7:00 PM). One hour after the first treatment (8:00 AM), rats in groups Model, O-treated, GH-treated and GL-treated were injected intraperitoneally (i.p.) with 6 mg/kg cisplatin, and the other groups were injected i.p. with saline of equal volume. The consumption of kaolin of the rats were measured. All the rats were anesthetized by i.p. injection of pentobarbital sodium at 24 h post-cisplatin. After blood samples were taken, medulla oblongata and ileum were removed. The levels of 5-HT and its metabolite 5-HIAA in ileum, medulla oblongata and serum were determined using high-performance liquid chromatography with electrochemical detection (HPLC-ECD). The mRNA expression levels of 5-HT3 receptor, tryptophan hydroxylase (TPH), monoamine oxidase A (MAO-A) and serotonin reuptake transporter (SERT) were detected by real-time PCR. The protein expression levels and distribution of 5-HT3 receptor, TPH and MAO-A in the medulla oblongata and ileum were measured by Western blotting and immunohistochemistry, respectively. RESULTS: [6]-gingerol treatment significantly reduced the kaolin ingestion and the increase in 5-HT concentration in rats induced by cisplatin. TPH, MAO-A, SERT, and 5-HT3 receptor are important in 5-HT metabolism, and cisplatin-induced alterations in the associated protein/mRNA levels were restored when treated with [6]-gingerol. CONCLUSION: This suggests that the antiemetic effect of [6]-gingerol against cisplatin-induced emesis may be due to 5-HT attenuation via modulating the TPH/MAO-A/SERT/5-HT/5-HT3 receptor system.

RNA-Seq reveals inflammatory mechanisms of Xiao-Ban-Xia-Tang decoction to ameliorate cisplatin-induced emesis in a rat pica model.

OBJECTIVES: Xiao-Ban-Xia-Tang decoction (XBXT), an antiemetic formula in traditional Chinese medicine, has been proved to be a potential treatment for chemotherapy-induced nausea and vomiting (CINV), but the underlying mechanisms are not adequately understood. This study aimed to investigate changes in the ileum transcriptome after cisplatin and XBXT treatment and to reveal whether the antiemetic mechanisms of XBXT are related to its anti-inflammatory effect. METHODS: The pica model was established by a single intraperitoneal injection of 6 mg/kg cisplatin in Wistar rats. Tissues from the gastric antrum and ileum were stained with hematoxylin-eosin to observe gastrointestinal tract pathological changes. Based on the differentially expressed genes (DEGs) which were altered by cisplatin and reversed by XBXT, the transcriptome data of rat ileum were analyzed by GO, KEGG, and PPI analyses. Several inflammatory DEGs were validated by RT-PCR. RESULTS: XBXT could reduce kaolin intake up to 72 h after modeling and alleviate the inflammatory damage of gastric antrum and ileum induced by cisplatin. According to the transcriptome profile, there were 75 DEGs down-regulated by cisplatin and up-regulated by XBXT and 343 DEGs up-regulated by cisplatin and down-regulated by XBXT. XBXT could blunt the overexpression of tryptophan hydroxylase 1 (the rate-limiting enzyme of serotonin synthesis) in ileum. Enrichment analysis showed that inhibiting overexpression of several conventional inflammation pathways and pro-inflammation cytokines were related to the antiemetic effectiveness of XBXT. CONCLUSIONS: This study implies that inhibiting inflammatory signaling pathways and synthesis of serotonin might be potential mechanisms of XBXT's antiemetic effect against CINV.

The Antiemetic Effect of Xiao-Ban-Xia-Tang Formula against Cisplatin-Induced Emesis is Mediated through Inhibition of NLRP3 Inflammasome Activation in a Rat Pica Model.

Xiao-Ban-Xia-Tang (XBXT), a traditional Chinese medicine formula, has been used for the treatment of emesis for nearly 2000 years, but its underlying mechanism is not yet fully clarified. The purpose of this study is to reveal the antiemetic mechanisms of XBXT by focusing on the NLRP3 inflammasome pathway in a chemotherapy-induced rat pica model. The pica model was generated by a single intraperitoneal injection of cisplatin in this study. Consumption of kaolin (a type of clay) and food and body weight were recorded every 24 hours. Cisplatin-induced increase in kaolin consumption (pica) was used to quantify chemotherapy-induced nausea and vomiting (CINV). Tissue from the ileum and antrum was stained with hematoxylin eosin (HE) to observe pathological changes. The levels of reactive oxygen species (ROS) and inflammatory cytokines, including IL-1ß and IL-18 in serum, were detected by ELISA. In addition, changes in the NLRP3 inflammasome activation in the ileum and antrum were investigated using western blot and immunofluorescence microscopy. The results showed that oral administration of XBXT and ondansetron inhibited acute and delayed pica and significantly protected against the gastrointestinal pathological injury induced by cisplatin. The levels of ROS, IL-1ß, and IL-18 in the serum of cisplatin-treated rats were also remarkably decreased by XBXT and ondansetron. Moreover, we found that XBXT can inhibit cisplatin-induced NLRP3 inflammasome activation. The present study indicates that the inhibition of the NLRP3 inflammasome activation might be one of the potential mechanisms for the therapeutic effects of XBXT against CINV.

Effects of ondansetron and [6]-gingerol on pica and gut microbiota in rats treated with cisplatin.

PURPOSE: [6]-gingerol is one of the main components of ginger with many biological activities. In this study, the effects of ondansetron and [6]-gingerol on pica and gut microbiota in rats injected with cisplatin were evaluated. MATERIALS AND METHODS: Rat model of cisplatin-induced pica was established, and the effects of ondansetron and [6]-gingerol on the gut microbiota were further studied by 16S rDNA gene analysis. RESULTS: The results showed that the total intake of kaolin of the rats injected with cisplatin was significantly increased, and treatment of ondansetron and [6]-gingerol in advance could significantly ameliorate the pica induced by cisplatin. The body weight of the rats injected with cisplatin was decreased compared with the control group. The 16S rDNA gene analysis has shown that ondansetron, [6]-gingerol and cisplatin could increase the relative abundance of Bacteroidetes and decrease Firmicutes on phylum level. CONCLUSION: [6]-gingerol was as effective as ondansetron in the treatment of pica induced by cisplatin in rats, and it seemed that [6]-gingerol had the potential to ameliorate the alteration of gut microbiome, but it needs further study.

The Chinese Linguistic Validation of the Ureteral Stent Symptom Questionnaire.

OBJECTIVE: We validated the Chinese version of the Ureteral Stent Symptoms Questionnaire (USSQ) in patients with an indwelling ureteric stent. PATIENTS AND METHODS: The English version of the USSQ was translated into Chinese using a multi-step process by 3 urologists and 2 independent translators. The Chinese version was validated by asking 50 patients with temporary unilateral ureteral stent to complete the questionnaire at weeks 1 and 4 after stent placement. Thirty healthy individuals without a ureteral stent were also asked to complete the Chinese USSQ once. The psychometric properties of the questionnaire were analyzed. RESULTS: After revision of the initial 2 drafts after translation, back translation, and pilot testing, a final draft was developed that underwent field testing. Psychometric analyses revealed satisfactory internal consistencies and test-retest reliability for all domains except for sexual matters. Most USSQ domains showed moderate correlations with each other. It demonstrated satisfactory discriminant validity (sensitivity to change, p < 0.05) and test-retest reliability. Analysis of the domains of the sexual matters was limited because of the small proportion of the study population for whom it was applicable. CONCLUSION: The Chinese version of the USSQ is a reliable and valid instrument to evaluate symptoms and health-related quality of life in Chinese patients with ureteric stents.

Connective tissue growth factor is not necessary for haze formation in excimer laser wounded mouse corneas.

We sought to determine if connective tissue growth factor (CTGF) is necessary for the formation of corneal haze after corneal injury. Mice with post-natal, tamoxifen-induced, knockout of CTGF were subjected to excimer laser phototherapeutic keratectomy (PTK) and the corneas were allowed to heal. The extent of scaring was observed in non-induced mice, heterozygotes, and full homozygous knockout mice and quantified by macrophotography. The eyes from these mice were collected after euthanization for re-genotyping to control for possible Cre-mosaicism. Primary corneal fibroblasts from CTGF knockout corneas were established in a gel plug assay. The plug was removed, simulating an injury, and the rate of hole closure and the capacity for these cells to form light reflecting cells in response to CTGF and platelet-derived growth factor B (PDGF-B) were tested and compared to wild-type cells. We found that independent of genotype, each group of mice was still capable of forming light reflecting haze in the cornea after laser ablation (p = 0.40). Results from the gel plug closure rate in primary cell cultures of knockout cells were not statistically different from serum starved wild-type cells, independent of treatment. Compared to the serum starved wild-type cells, stimulation with PDGF-BB significantly increased the KO cell culture's light reflection (p = 0.03). Most interestingly, both reflective cultures were positive for α-SMA, but the cellular morphology and levels of α-SMA were distinct and not in proportion to the light reflection seen. This new work demonstrates that corneas without CTGF can still form sub-epithelial haze, and that the light reflecting phenotype can be reproduced in culture. These data support the possibilities of growth factor redundancy and that multiple pro-haze pathways exist.

Increased maternal nighttime cortisol concentrations in late gestation alter glucose and insulin in the neonatal lamb.

Previous studies in our laboratory have shown that a modest chronic increase in maternal cortisol concentrations impairs maternal glucose metabolism and increases the incidence of perinatal stillbirth. The dramatic outcomes prevented our ability to study the effects of maternal hypercortisolemia on neonatal growth, glucose metabolism, and hypothalamo-pituitary-adrenal axis response. Therefore, we developed a model in which pregnant ewes are infused for 12 h/day at 0.5 mg·kg(-1)·day(-1) from day 115 of gestation until delivery (~145), elevating nighttime plasma cortisol concentrations. This pattern of elevation of cortisol mimics that in patients with elevated evening cortisol concentrations, as in Cushing's syndrome or chronic depression. Plasma cortisol, glucose, insulin, and electrolytes were measured during pregnancy and postpartum in control and cortisol-infused ewes and their postnatal lambs for the first 14 days after delivery. Neonatal growth and plasma ACTH, aldosterone, renin activity, and electrolytes, and organ weights at 14 days of age were also measured. Infusion of cortisol increased maternal plasma cortisol during pregnancy but not postpartum, and did not alter neonatal ACTH or cortisol. Although maternal glucose and insulin concentrations were not changed by the maternal infusion of cortisol, neonatal plasma glucose was increased and plasma insulin was decreased compared to those in the control group. Neonatal ponderal index and kidney weight were reduced, left ventricular wall thickness was increased, and plasma sodium and creatinine were increased after maternal cortisol infusion. These results suggest that excess maternal cortisol concentrations in late gestation alter growth, glucose and insulin regulation, and organ maturation in the neonate.

Elevated maternal cortisol leads to relative maternal hyperglycemia and increased stillbirth in ovine pregnancy.

In normal pregnancy, cortisol increases; however, further pathological increases in cortisol are associated with maternal and fetal morbidities. These experiments were designed to test the hypothesis that increased maternal cortisol would increase maternal glucose concentrations, suppress fetal growth, and impair neonatal glucose homeostasis. Ewes were infused with cortisol (1 mg·kg(-1)·day(-1)) from day 115 of gestation to term; maternal glucose, insulin, ovine placental lactogen, estrone, progesterone, nonesterified free fatty acids (NEFA), ß-hydroxybutyrate (BHB), and electrolytes were measured. Infusion of cortisol increased maternal glucose concentration and slowed the glucose disappearance after injection of glucose; maternal infusion of cortisol also increased the incidence of fetal death at or near parturition. The design of the study was altered to terminate the study prior to delivery, and post hoc analysis of the data was performed to test the hypothesis that maternal metabolic factors predict the fetal outcome. In cortisol-infused ewes that had stillborn lambs, plasma insulin was increased relative to control ewes or cortisol-infused ewes with live lambs. Maternal cortisol infusion did not alter maternal food intake or plasma NEFA, BHB, estrone, progesterone or placental lactogen concentrations, and it did not alter fetal body weight, ponderal index, or fetal organ weights. Our study suggests that the adverse effect of elevated maternal cortisol on pregnancy outcome may be related to the effects of cortisol on maternal glucose homeostasis, and that chronic maternal stress or adrenal hypersecretion of cortisol may create fetal pathophysiology paralleling some aspects of maternal gestational diabetes.

Changes in alpha1-adrenoceptor and NGF/proNGF pathway: a possible mechanism in diabetic urethral dysfunction.

OBJECTIVE: To investigate the changes in the α1-adrenoceptor and nerve growth factor (NGF)/NGF precursor (proNGF) pathway in the urethra after diabetes induction. MATERIALS AND METHODS: Urethral relaxation function was determined by simultaneous recordings of intravesical pressure under isovolumetric conditions and urethral perfusion pressure (UPP) in diabetic rats. The expression of α1-adrenoceptor, NGF, proNGF, low-affinity p75 receptor for neurotrophins (p75(NTR)) and sortilin in the urethras was measured using real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay and Western blotting. RESULTS: In diabetic rats, the lowest urethral pressure (UPP nadir) during urethral relaxation was significantly higher. Intravenous administration of tamsulosin, an α1-adrenoceptor antagonist, significantly decreased the UPP nadir and baseline UPP in diabetic rats. RT-qPCR and Western blotting studies showed a statistically significant increase of α1a- and α1b-adrenoceptor in the urethras from the diabetic group (p < 0.05). The expression of NGF was significantly decreased in the urethras from the diabetic group while the expression of proNGF was significantly increased (p < 0.05). The p75(NTR) level in the urethras of diabetic rats was decreased compared with controls (p < 0.05) and there was no significant difference regarding sortilin between the two groups (p > 0.05). CONCLUSION: This study validated the diabetic urethral dysfunction and furthermore indicated that the increase in the expression of α1-adrenoceptor and changes in the NGF/proNGF pathway may be involved in diabetic urethral dysfunction.

Cannabinoid receptors 1 and 2 are associated with bladder dysfunction in an experimental diabetic rat model.

OBJECTIVE: To investigate diabetes-associated changes in urinary bladder expression of cannabinoid receptors 1 and 2 (CB1 and CB2) and the functional role of CB agonists and antagonists in mediating phasic contractions of isolated bladder strips using a streptozotocin-induced diabetic rat model. MATERIALS AND METHODS: The bladder and dorsal root ganglion (DRG) were removed from diabetic rats and age-matched controls 8-10 weeks after diabetes induction. Expression of CB1 and CB2 mRNA was studied using quantitative real-time PCR and protein levels were determined by Western blot analysis. The effect of increasing concentrations (0.1-100 µM) of the mixed CB1/CB2 agonist R(+)-WIN 55,212-2 (WIN), selective CB1 antagonist (AM251) and selective CB2 antagonist (AM630) on carbachol-evoked contraction of bladder strips from control and diabetic rats was investigated. WIN-induced alterations of bladder strip contraction were then studied after pre-incubation with AM251 and AM630. RESULTS: Diabetes induced decreased CB1 protein and mRNA expression in both the bladder and DRG (P < 0.05), while decreased CB2 expression was observed in the bladder (P < 0.05). WIN decreased the amplitude, but not frequency, of carbachol-induced phasic contractions of bladder strips in a concentration-dependent manner and this effect was diminished in the diabetic state. AM630 and AM251 had no effect on isolated detrusor muscle function. Moreover, pre-incubation with AM251 partially counteracted the effect of WIN on detrusor muscle contraction. CONCLUSION: The results indicate that CB1 and CB2 are responsible for the pathogenesis of bladder dysfunction in diabetes mellitus and represent a viable target for pharmacological treatment of bladder cystopathy.

Cortisol stimulates proliferation and apoptosis in the late gestation fetal heart: differential effects of mineralocorticoid and glucocorticoid receptors.

We have previously found that modest chronic increases in maternal cortisol result in an enlarged fetal heart. To explore the mechanisms of this effect, we used intrapericardial infusions of a mineralocorticoid receptor (MR) antagonist (canrenoate) or of a glucocorticoid receptor (GR) antagonist (mifepristone) in the fetus during maternal infusion of cortisol (1 mg·kg⁻¹·day⁻¹). We have shown that the MR antagonist blocked the increase in fetal heart weight and in wall thickness resulting from maternal cortisol infusion. In the current study we extended those studies and found that cortisol increased Ki67 staining in both ventricles, indicating cell proliferation, but also increased active caspase-3 staining in cells of the conduction pathway in the septum and subendocardial layers of the left ventricle, suggesting increased apoptosis in Purkinje fibers. The MR antagonist blocked the increase in cell proliferation, whereas the GR antagonist blocked the increased apoptosis in Purkinje fibers. We also found evidence of activation of caspase-3 in c-kit-positive cells, suggesting apoptosis in stem cell populations in the ventricle. These studies suggest a potentially important role of corticosteroids in the terminal remodeling of the late gestation fetal heart and suggest a mechanism for the cardiac enlargement with excess corticosteroid exposure.

Prophylactic intra-aortic balloon pump reduces C-reactive protein levels and early mortality in high-risk patients undergoing percutaneous coronary intervention.

OBJECTIVE: Intra-aortic balloon pump (IABP) plays a pivotal role in the treatment of cardiogenic shock complicating acute myocardial infarction. However, the usefulness of prophylactic IABP support in high-risk patients during percutaneous coronary intervention (PCI) is still controversial, and its influence on the inflammatory response following PCI has not been well evaluated. In this study we sought to assess the impact of prophylactic IABP support upon C-reactive protein (CRP) level and clinical prognosis in high-risk patients undergoing PCI. METHODS AND RESULTS: A total of 106 high-risk patients diagnosed with acute ST-elevation or non-ST-elevation myocardial infarction (Cardiogenic shock was excluded) were enrolled and divided into two groups at random: 51 cases receiving PCI accompanied by prophylactic IABP support, and the remaining 55 cases undergoing PCI without IABP insertion served as the control group. CRP levels were determined on admission, day 3 and day 7, respectively. The troponin I (TNI) peak, left ventricular functions and major adverse cardiovascular events (MACE) were compared during follow-up. We found that the IABP group had a lower TNI peak as well as CRP level after PCI. Left ventricular function was improved at 2-week instead of 3-month followup. Although the mortality did not reach a significant decline after 6-month follow-up, it had improved in-hospital and at 30-day follow-up. CONCLUSION: The use of a prophylactic IABP in high-risk patients before PCI could reduce the CRP level and reduce mortality during the early phase following PCI.

Intra-aortic balloon pump improves clinical prognosis and attenuates C-reactive protein level in acute STEMI complicated by cardiogenic shock.

OBJECTIVES: Intra-aortic balloon pump (IABP) plays a pivotal role in the treatment of cardiogenic shock (CS) complicating acute ST-segment elevation myocardial infarction (STEMI). However, the influence of IABP on the inflammatory response has not been well evaluated. We sought to assess the effects of IABP support upon C-reactive protein (CRP) levels in patients with STEMI complicated by CS undergoing percutaneous coronary intervention (PCI). METHODS: This was a prospective study and a total of 91 patients with STEMI complicated by CS receiving emergency PCI were enrolled, 43 cases of which received IABP support, and the remaining cases without IABP therapy were the control group. CRP levels were determined at admission, and on days 3 and 7. Troponin I peak, left ventricular function and major adverse cardiovascular events were compared following PCI. RESULTS: The IABP group had lower CRP levels at days 3 and 7, greater improvement in left ventricular function and lower troponin peak following PCI. Significant differences were also observed in the incidence of mortality at 6-month follow-up, both in hospital and after 30 days. CONCLUSIONS: IABP support improves clinical prognosis and attenuates the CRP level in patients with CS complicating STEMI after PCI.

Expression of ENaC subunits, chloride channels, and aquaporins in ovine fetal lung: ontogeny of expression and effects of altered fetal cortisol concentrations.

Transition of the epithelium of the fetal lung from fluid secretion to fluid reabsorption requires changes in the expression of ion channels. Corticosteroids regulate expression of several of these channels, including the epithelium sodium channel (ENaC) subunits and aquaporins (AQP). We investigated the ontogenetic changes in these ion channels in the ovine fetal lung during the last half of gestation, a time of increasing adrenal maturation. Expression of the mRNAs for the chloride channels, cystic fibrosis transmembrane conductance regulator (CFTR), and chloride channel 2 (CLCN2) decreased with age. Expression of mRNAs for AQP1, AQP5, and for subunits of ENaC (alpha, beta, gamma) increased with age. In the fetal sheep the expression of ENaCbeta mRNA was dramatically higher than the expression of ENaCalpha or ENaCgamma, but expression of ENaCbeta protein decreased with maturation, although the ratio of the mature (112 kDa) to immature (102 kDa) ENaCbeta protein increased with age, particularly in the membrane fraction. In contrast, ENaCalpha mRNA and protein both increase with maturation, and the mature form of ENaCalpha (68 kDa) predominates at all ages. A modest increase in fetal cortisol, within the range expected to occur naturally in late gestation but prior to active labor, increased ENaCalpha mRNA but not ENaCbeta, ENaCgamma, or AQP mRNAs. We conclude that in the ovine fetal lung, appearance of functional sodium channels is associated with induction of ENACalpha and ENaCgamma, and that ENaCalpha expression may be induced by even small, preterm increases in fetal cortisol.