Performance of current ultrasound-based malignancy risk stratification systems for thyroid nodules in patients with follicular neoplasms.

OBJECTIVES: To investigate the ability of the currently used ultrasound-based malignancy risk stratification systems for thyroid neoplasms (ATA, AACE/ACE/AME, K-TIRADS, EU-TIRADS, ACR-TIRADS and C-TIRADS) in distinguishing follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA). Additionally, we evaluated the ability of these systems in correctly determining the indication for biopsy. METHODS: Three hundred twenty-nine follicular neoplasms with definitive postoperative histopathology were included. The nodules were categorized according to each of six stratification systems, based on ultrasound findings. We dichotomized nodules into the positive predictive group of FTC (high and intermediate risk) and negative group of FTC based on the classification results. Missed biopsy was defined as neoplasms that were diagnosed as FTCs but for which biopsy was not indicated based on lesion classification. Unnecessary biopsy was defined as neoplasms that were diagnosed as FTAs but for whom biopsy was considered indicated based on classification. The diagnostic performance and missed and unnecessary biopsy rates were evaluated for each stratification system. RESULTS: The area under the curve of each system for distinguishing follicular neoplasms was < 0.700 (range, 0.511-0.611). The missed biopsy rates were 9.0-22.4%. The missed biopsy rates for lesions ≤ 4 cm and lesions sized 2-4 cm were 16.2-35.1% and 0-20.0%, respectively. Unnecessary biopsy rates were 65.3-93.1%. In ≤ 4 cm group, the unnecessary biopsy rates were 62.2-89.7%. CONCLUSION: The malignancy risk stratification systems can select appropriate nodules for biopsy in follicular neoplasms, while they have limitations in distinguishing follicular neoplasms and reducing unnecessary biopsy. Specific stratification systems and recommendations should be established for follicular neoplasms. KEY POINTS: • Current ultrasound-based malignancy risk stratification systems of thyroid nodules had low efficiency in the characterization of follicular neoplasms. • The adopted stratification systems showed acceptable performance for selecting FTC for biopsy but unsatisfactory performance for reducing unnecessary biopsy.

A uropathogenic E. coli UTI89 model of prostatic inflammation and collagen accumulation for use in studying aberrant collagen production in the prostate.

Bacterial infection is one known etiology of prostatic inflammation. Prostatic inflammation is associated with prostatic collagen accumulation and both are linked to progressive lower urinary tract symptoms in men. We characterized a model of prostatic inflammation using transurethral instillations of Escherichia coli UTI89 in C57BL/6J male mice with the goal of determining the optimal instillation conditions, understanding the impact of instillation conditions on urinary physiology, and identifying ideal prostatic lobes and collagen 1a1 prostatic cell types for further analysis. The smallest instillation volume tested (50 µL) distributed exclusively to the bladder, 100- and 200-µL volumes distributed to the bladder and prostate, and a 500-µL volume distributed to the bladder, prostate, and ureter. A threshold optical density of 0.4 E. coli UTI89 in the instillation fluid was necessary for significant (P < 0.05) prostate colonization. E. coli UTI89 infection resulted in a low frequency, high volume spontaneous voiding pattern. This phenotype was due to exposure to E. coli UTI89, not catheterization alone, and was minimally altered by a 50-µL increase in instillation volume and doubling of E. coli concentration. Prostate inflammation was isolated to the dorsal prostate and was accompanied by increased collagen density. This was partnered with increased density of protein tyrosine phosphatase receptor type C+, procollagen type I-α1+ copositive cells and decreased density of α2-smooth muscle actin+, procollagen type I-α1+ copositive cells. Overall, we determined that this model is effective in altering urinary phenotype and producing prostatic inflammation and collagen accumulation in mice.

The influence of intermittent hypoxia, obesity, and diabetes on male genitourinary anatomy and voiding physiology.

We used male BTBR mice carrying the Lepob mutation, which are subject to severe and progressive obesity and diabetes beginning at 6 wk of age, to examine the influence of one specific manifestation of sleep apnea, intermittent hypoxia (IH), on male urinary voiding physiology and genitourinary anatomy. A custom device was used to deliver continuous normoxia (control) or IH to wild-type and Lepob/ob (mutant) mice for 2 wk. IH was delivered during the 12-h inactive (light) period in the form of 90 s of 6% O2 followed by 90 s of room air. Continuous room air was delivered during the 12-h active (dark) period. We then evaluated genitourinary anatomy and physiology. As expected for the type 2 diabetes phenotype, mutant mice consumed more food and water, weighed more, and voided more frequently and in larger urine volumes. They also had larger bladder volumes but smaller prostates, seminal vesicles, and urethras than wild-type mice. IH decreased food consumption and increased bladder relative weight independent of genotype and increased urine glucose concentration in mutant mice. When evaluated based on genotype (normoxia + IH), the incidence of pathogenic bacteriuria was greater in mutant mice than in wild-type mice, and among mice exposed to IH, bacteriuria incidence was greater in mutant mice than in wild-type mice. We conclude that IH exposure and type 2 diabetes can act independently and together to modify male mouse urinary function. NEW & NOTEWORTHY Metabolic syndrome and obstructive sleep apnea are common in aging men, and both have been linked to urinary voiding dysfunction. Here, we show that metabolic syndrome and intermittent hypoxia (a manifestation of sleep apnea) have individual and combined influences on voiding function and urogenital anatomy in male mice.

Impact of sex, androgens, and prostate size on C57BL/6J mouse urinary physiology: urethral histology.

The National Institutes of Health leveled new focus on sex as a biological variable with the goal of understanding sex-specific differences in health and physiology. We previously published a functional assessment of the impact of sex, androgens, and prostate size on C57BL/6J mouse urinary physiology (Ruetten H, Wegner KA, Zhang HL, Wang P, Sandhu J, Sandhu S, Mueller B, Wang Z, Macoska J, Peterson RE, Bjorling DE, Ricke WA, Marker PC, Vezina CM. Am J Physiol Renal Physiol 317: F996-F1009, 2019). Here, we measured and compared five characteristics of urethral histology (urethral lumen diameter and area, epithelial cell count, epithelial and rhabdosphincter thickness, epithelial cell area, and total urethral area) in male and female 9-wk-old C57BL/6J mice using hematoxylin and eosin staining. We also compared male mice with castrated male mice, male and female mice treated with the steroid 5α-reductase inhibitor finasteride or testosterone, or male mice harboring alleles (Pbsn4cre/+; R26RDta/+) that reduce prostate lobe mass. The three methods used to reduce prostate mass (castration, finasteride, and Pbsn4cre/+; R26RDta/+) changed urethral histology, but none feminized male urethral histology (increased urethral epithelial area). Exogenous testosterone caused increased epithelial cell count in intact females but did not masculinize female urethral histology (decrease epithelial area). Our results lay a critical foundation for future studies as we begin to parse out the influence of hormones and cellular morphology on male and female urinary function.

Impact of sex, androgens, and prostate size on C57BL/6J mouse urinary physiology: functional assessment.

Laboratory mice are used to identify causes of urinary dysfunction including prostate-related mechanisms of lower urinary tract symptoms. Effective use of mice for this purpose requires a clear understanding of molecular, cellular, anatomic, and endocrine contributions to voiding function. Whether the prostate influences baseline voiding function has not been specifically evaluated, in part because most methods that alter prostate mass also change circulating testosterone concentrations. We performed void spot assay and cystometry to establish a multiparameter "baseline" of voiding function in intact male and female 9-wk-old (adult) C57BL/6J mice. We then compared voiding function in intact male mice to that of castrated male mice, male (and female) mice treated with the steroid 5α-reductase inhibitor finasteride, or male mice harboring alleles (Pbsn4cre/+; R26RDta/+) that significantly reduce prostate lobe mass by depleting prostatic luminal epithelial cells. We evaluated aging-related changes in male urinary voiding. We also treated intact male, castrate male, and female mice with exogenous testosterone to determine the influence of androgen on voiding function. The three methods used to reduce prostate mass (castration, finasteride, and Pbsn4cre/+; R26RDta/+) changed voiding function from baseline but in a nonuniform manner. Castration feminized some aspects of male urinary physiology (making them more like intact female mice) while exogenous testosterone masculinized some aspects of female urinary physiology (making them more like intact male mice). Our results provide evidence that circulating testosterone is responsible in part for baseline sex differences in C57BL/6J mouse voiding function while prostate lobe mass in young, healthy adult mice has a lesser influence.

Insight and Resources From a Study of the "Impact of Sex, Androgens, and Prostate Size on C57BL/6J Mouse Urinary Physiology.

The purpose of this symposium report is to summarize information from a session 3 oral presentation at the Society of Toxicologic Pathology Annual Symposium in Raleigh, North Carolina. Mice are genetically tractable and are likely to play an important role in elucidating environmental, genetic, and aging-related mechanisms of urinary dysfunction in men. We and others have made significant strides in developing quantitative methods for assessing mouse urinary function and our collaborators recently showed that aging male mice, like men, develop urinary dysfunction. Yet, it remains unclear how mouse prostate anatomy and histology relate to urinary function. The purpose of this report is to share foundational resources for evaluating mouse prostate histology and urinary physiology from our recent publication "Impact of Sex, Androgens, and Prostate Size on C57BL/6J Mouse Urinary Physiology: Functional Assessment." We will begin with a review of prostatic embryology in men and mice, then move to comparative histology resources, and conclude with quantitative measures of rodent urinary physiology.

Antibacterial mechanism of chelerythrine isolated from root of Toddalia asiatica (Linn) Lam.

BACKGROUND: Antimicrobial resistance was one of serious worldwide problems confused many researchers. To solve this problem, we explored the antibacterial effect of chelerythrine, a natural compound from traditional Chinese medicine and studied its action. METHODS: The contents of chelerythrine from different fractions of Toddalia asiatica (Linn) Lam (T. asiatica) were determined. The anti-bacterial activities of chelerythrine were tested by disc diffusion method (K-B method). Scanning electron microscopy (SEM), alkaline phosphatase (AKP), bacterial extracellular protein leakage and SDS-PAGE analysis were also used to investigate the antibacterial mechanism of chelerythrine. RESULTS: Analytic results of High Performance Liquid Chromatography showed that the content of chelerythrine (1.97 mg/g) in the ethyl acetate fraction was the highest, followed by those of methanol fraction and petroleum ether fraction. The in vitro anti-bacterial mechanisms of chelerythrine from T. asiatica were assessed. Chelerythrine showed strong antibacterial activities against Gram-positive bacteria, Staphylococcus aureus (SA), Methicillin-resistant S. aureus (MRSA), and extended spectrum ß-lactamase S. aureus (ESBLs-SA). The minimum inhibitory concentrations (MICs) of chelerythrine on three bacteria were all 0.156 mg/mL. Furthermore, results suggested that the primary anti-bacterial mechanism of chelerythrine may be attributed to its destruction of the channels across the bacterial cell membranes, causing protein leakage to the outside of the cell, and to its inhibition on protein biosynthesis. Images of scanning electron microscope revealed severe morphological changes in chelerythrine-treated bacteria except control, damage of parts of the cell wall and cell membrane as well as the leakage of some substances. CONCLUSIONS: Chelerythrine isolated from root of Toddalia asiatica (Linn) Lam possesses antibacterial activities through destruction of bacterial cell wall and cell membrance and inhibition of protein biosynthesis.

Impact of a folic acid-enriched diet on urinary tract function in mice treated with testosterone and estradiol.

Aging men are susceptible to developing lower urinary tract symptoms, but the underlying etiology is unknown and the influence of dietary and environmental factors on them is unclear. We tested whether a folic acid-enriched diet changed urinary tract physiology and biology in control male mice and male mice with urinary dysfunction induced by exogenous testosterone and estradiol (T+E2), which mimics changing hormone levels in aging humans. T+E2 treatment increased mouse urine output, time between voiding events, and bladder capacity and compliance. Consumption of a folic acid-enriched diet moderated these changes without decreasing prostate wet weight or threshold voiding pressure. One potential mechanism for these changes involves water balance. T+E2 treatment increases plasma concentrations of anti-diuretic hormone, which is offset at least in part by a folic acid-enriched diet. Another potential mechanism involves neural control of micturition. The folic acid-enriched diet, fed to T+E2-treated mice, increased voiding frequency in response to intravesicular capsaicin infusion and increased mRNA abundance of the capsaicin-sensitive cation channel transient receptor potential vanilloid subfamily member 1 (Trpv1) in L6 and S1 dorsal root ganglia (DRG) neurons. T+E2 treatment and a folic acid-enriched diet also modified DNA methylation, which is capable of altering gene expression. We found the enriched diet increased global DNA methylation in dorsal and ventral prostate and L6 and S1 DRG. Our results are consistent with folic acid acting to slow or reverse T+E2-mediated alteration in urinary function in part by normalizing water balance and enhancing or preserving afferent neuronal function.

Treatment with a cannabinoid receptor 2 agonist decreases severity of established cystitis.

PURPOSE: We investigated whether treatment with the selective cannabinoid receptor 2 agonist GP1a would ameliorate the severity of experimental cystitis. We determined the association of referred hyperalgesia and increased urinary frequency after establishing cystitis in mice by intravesical instillation of acrolein. MATERIALS AND METHODS: Cystitis was induced by intravesical instillation of acrolein in female C57BL/6NH mice. Mice were treated with GP1a (10 mg/kg intraperitoneally) or vehicle 3.5, 22 and 30 hours after instillation of acrolein. Mice were tested for mechanical sensitivity of hind paws. Short-term voluntary voiding was assessed by quantifying urine spots of freely moving mice. Bladders were collected, weighed and processed for immunohistochemical, histological and immunoblotting analysis. RESULTS: At 48 hours after acrolein instillation the bladder of all mice showed histological evidence of inflammation. The severity of edema and increase in bladder weight were inhibited in cannabinoid receptor 2 agonist treated animals (p <0.05). Neither cystitis nor treatment with GP1a or AM630 (selective cannabinoid receptor 2 antagonist) plus GP1a appeared to alter cannabinoid receptor 2-like immunoreactivity abundance in urothelium. Mechanical sensitivity was significantly increased after acrolein and the increase was attenuated in cannabinoid receptor 2 agonist treated mice (p <0.05). The number of small diameter urine spots was significantly increased after acrolein and treatment with GP1a attenuated this increase (p <0.05). GP1a effects were prevented by AM630. CONCLUSIONS: Treatment with a selective cannabinoid receptor 2 agonist decreased severity of established acrolein induced cystitis and inhibited bladder inflammation associated increased referred mechanical sensitivity and increased bladder urinary frequency. Our data indicate that cannabinoid receptor 2 is a potential therapeutic target for treatment of painful inflammatory bladder diseases.

Activation of cannabinoid receptor 2 inhibits experimental cystitis.

Cannabinoids have been shown to exert analgesic and anti-inflammatory effects, and the effects of cannabinoids are mediated primarily by cannabinoid receptors 1 and 2 (CB1and CB2). Both CB1 and CB2 are present in bladders of various species, including human, monkey, and rodents, and it appears that CB2 is highly expressed in urothelial cells. We investigated whether treatment with the CB2 agonist GP1a alters severity of experimental cystitis induced by acrolein and referred mechanical hyperalgesia associated with cystitis. We also investigated whether the mitogen-activated protein kinases (MAPK), ERK1/2, p38, and JNK are involved in the functions of CB2. We found that treatment with the selective CB2 agonist GP1a (1-10 mg/kg, ip) inhibited the severity of bladder inflammation 3 h after intravesical instillation of acrolein in a dose-dependent manner, and inhibition reached significance at a dose of 10 mg/kg (P < 0.05). Treatment with GP1a (10 mg/kg) inhibited referred mechanical hyperalgesia associated with cystitis (P < 0.05). The inhibitory effects of the CB2 agonist were prevented by the selective CB2 antagonist AM630 (10 mg/kg, sc). We further demonstrated the inhibitory effects of CB2 appear to be at least partly mediated by reducing bladder inflammation-induced activation of ERK1/2 MAPK pathway. The results of the current study indicate that CB2 is a potential therapeutic target for treatment of bladder inflammation and pain in patients.

[Advance in studies on pharmacological activities of chelerythrine].

Chelerythrine is a kind of benzo[c] phenanthridine alkaloids, with such pharmacological activities as antitumor, antibiosis and anti-inflammation, which is widely found in plant of Fumariaceae, Papaveraceae, Ranunculaceae and Rutaceae families. This article summarizes the advances in domestic and foreign studies on pharmacological effect of chelerythrine in the recent decade, in the expectation of providing scientific basis for the in-depth studies, development and utilization of chelerythrine.

Image-guided Thermal Ablation as a Promising Approach to Both Nontoxic and Toxic Autonomously Functioning Thyroid Nodules.

RATIONALE AND OBJECTIVES: Although thermal ablation has been recommended as an alternative therapy option for autonomously functioning thyroid nodules (AFTN), current clinical evidence mainly focuses on toxic AFTN. This study aims to evaluate and compare the efficacy and safety of thermal ablation (percutaneous radiofrequency ablation or microwave ablation) in treating nontoxic and toxic AFTN. MATERIALS AND METHODS: AFTN patients who received a single session of thermal ablation with a follow-up period ≥12 months were recruited. Changes in nodule volume and thyroid function, and complications were evaluated. Technical efficacy was defined as the maintenance or restoration of euthyroidism with a volume reduction rate (VRR) ≥80% at the last follow-up. RESULTS: In total, 51 AFTN patients (age: 43.8±13.9 years, female: 88.2%) with a median follow-up period of 18.0 (12.0-24.0) months were included, where 31 were nontoxic (nontoxic group), and 20 were toxic (toxic group) before ablation. The median VRR was 96.3% (80.1%-98.5%) and 88.3% (78.3%-96.2%) in the nontoxic and toxic groups, respectively, and the respective euthyroidism rates were 93.5% (29/31, 2 evolved to toxic) and 75.0% (15/20, 5 remained toxic). The corresponding technical efficacy was 77.4% (24/31) and 55.0% (11/20, p=0.126). Except for one case of stress-induced cardiomyopathy in the toxic group, no permanent hypothyroidism or other major complications occurred in both groups. CONCLUSION: Image-guided thermal ablation is efficacious and safe in treating AFTN, both nontoxic and toxic. Recognition of nontoxic AFTN would be helpful for treatment, efficacy evaluation, and follow-up.

The utility of serum anti-thyroglobulin antibody and thyroglobulin in the preoperative differential diagnosis of thyroid follicular neoplasms.

PURPOSE: Distinguishing follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA) before surgery is inherently challenging owing to the lack of malignant features on ultrasound, poor sensitivity of fine-needle biopsy, and the absence of definitive markers. We investigated whether thyroglobulin (Tg), anti-thyroglobulin antibody (TgAb), thyroid peroxidase antibodies (TPOAb), and thyroid stimulating hormone (TSH) can help differentiate FTC from FTA. METHODS: Data pertaining to 319 patients with follicular neoplasms were retrospectively analyzed. We compared the serum markers between patients with confirmed FTC and FTA. We also analyzed the prevalence of FTC in different subgroups of patients based on serum marker levels. RESULTS: TgAb was a risk factor for FTC. Compared to TgAb ≤11.68 IU/mL group, the odds ratio (OR) for FTC in TgAb 11.69-30.50 IU/mL group and TgAb >30.50 IU/mL group were 2.206 (1.114-4.369, P = 0.023) and 3.247 (1.684-6.260, P < 0.001), respectively. The prevalence of malignancy in TgAb >30.50 IU/mL group was significantly higher than in the TgAb ≤11.68 IU/mL group (32.9 vs. 13.1%, P = 0.001). In patients with TgAb (-) status, Tg was another risk factor for FTC. Compared to Tg ≤38.51 ng/mL group, OR of Tg >434.60 ng/mL group was 3.836 (1.625-9.058, P = 0.002); the prevalence of malignancy in the Tg >434.60 ng/mL group was 47.2% and higher than other groups. CONCLUSIONS: TgAb and Tg levels may be useful markers for preoperative differential diagnosis of follicular neoplasms. Higher TgAb and Tg levels were associated with greater malignant risk. Thus, we should be cautious of preoperative TgAb and Tg in follicular neoplasms.

Experimental Study on PVA-MgO Composite Improvement of Sandy Soil.

Materials with violent hydration reaction such as cement are used to solidify sandy soil slopes, which will cause destructive damage to the ecology of the slopes. In this paper, polyvinyl alcohol (PVA) and activated magnesium oxide (MgO) are used to improve sandy soil, and the effects of the dosage and curing age of modifiers on the mechanical properties of solidified sandy soil are studied. The dry-wet durability of the composite improved sandy soil is analyzed using a dry-wet cycle test, and the improvement mechanism of PVA and activated magnesium oxide is revealed using an electron microscope. The results show that the curing effect of polyvinyl alcohol and activated magnesium oxide on sand particles is better than that of polyvinyl alcohol alone. The compressive strength of improved soil samples increases with the increase of curing time, and magnesium oxide as an improved material needs appropriate reaction conditions to give full play to its role. The compressive strength of composite improved samples increases first and then decreases during the dry-wet cycle. Through the observation of microstructure, it can be seen that the cementing material wraps and connects the sand particles, and the cementing material of the sample after the dry-wet cycle develops more completely; if the magnesium oxide content is high, cracks may appear inside the sample.

Strength of Coarse-Grained Soil Stabilized by Poly (Vinyl Alcohol) Solution and Silica Fume under Wet-Dry Cycles.

To investigate an environmentally benign stabilizer for coarse-grained soil in southeast Tibet, poly (vinyl alcohol) (PVA) and silica fume were used to improve the geotechnical properties of coarse-grained soil. Unconfined compressive strength (UCS) and wet-dry cycle tests were conducted on prepared samples to evaluate the effect of the additive content and curing age on the strength and durability of coarse-grained soil. The results reveal that the UCS of the samples increased with the additive content of PVA solution and the curing age. The optimal value for the additive content of PVA solution and the curing age is 12% and 7 days, respectively. With the optimal PVA solution content, the PVA solution combined with silica fume stabilizer exhibited better reinforcement compared with pristine PVA. The UCS of the samples stabilized by PVA solution and silica fume increased depending on the curing age, and plateaued after 14 days. Samples with 12% PVA solution and 6% silica fume achieved a satisfactory UCS of 1543.17 kPa after curing for 28 days. As the number of wet-dry cycles increased, the UCS of the samples stabilized by the PVA solution and silica fume exhibited an upward trend during the first three wet-dry cycles, owing to the filling of pores by the gel produced by the silica fume, but began to decline as the number of wet-dry cycles increased. All samples retained a high UCS value after 10 wet-dry cycles compared with the samples that were not subjected to wet-dry cycles.

In utero and lactational PCB exposure drives anatomic changes in the juvenile mouse bladder.

Bladder dysfunction, including incontinence, difficulty emptying the bladder, or urgency to urinate is a pervasive health and quality of life concern. However, risk factors for developing these symptoms are not completely understood, and the influence of exposure to environmental chemicals, especially during development, on the formation and function of the bladder is understudied. Environmental contaminants such as polychlorinated biphenyls (PCBs) are known to pose a risk to the developing brain; however, their influence on the development of peripheral target organs, such as bladder, are unknown. To address this data gap, C57Bl/6J mouse dams were exposed to an environmentally-relevant PCB mixture at 0, 0.1, 1 or 6 mg/kg daily beginning two weeks prior to mating and continuing through gestation and lactation. Bladders were collected from offspring at postnatal days (P) 28-31. PCB concentrations were detected in bladders in a dose-dependent manner. PCB effects on the bladder were sex- and dose-dependent. Overall, PCB effects were observed in male, but not female, bladders. PCBs increased bladder volume and suburothelial ßIII-tubulin-positive nerve density compared to vehicle control. A subset of these nerves were sensory peptidergic axons indicated by increased calcitonin gene-related protein (CGRP) positive nerve fibers in mice exposed to the highest PCB dose compared to the lowest PCB dose. PCB-induced increased nerve density was also positively correlated with the number of mast cells in the bladder, suggesting inflammation may be involved. There were no detectable changes in epithelial composition or apoptosis as indicated by expression of cleaved caspase 3, suggesting PCBs do not cause overt toxicity. Bladder volume changes were not accompanied by changes in bladder mass or epithelial thickness, indicating that obstruction was not likely involved. Together, these results are the first to suggest that following developmental exposure, PCBs can distribute to the bladder and alter neuroanatomic development and bladder volume in male mice.

Genetic background but not prostatic epithelial beta-catenin influences susceptibility of male mice to testosterone and estradiol-induced urinary dysfunction.

Urinary voiding dysfunction in aging men can cause bothersome symptoms and irreparable tissue damage. Underlying mechanisms are not fully known. We previously demonstrated that subcutaneous, slow-release testosterone and estradiol implants (T+E2) drive a pattern of urinary voiding dysfunction in male mice that resembles that of aging men. The initial goal of this study was to test the hypothesis that prostatic epithelial beta-catenin (Ctnnb1) is required for T+E2-mediated voiding dysfunction. Targeted Ctnnb1 deletion did not significantly change voiding function in control or T+E2 treated mice but led to the surprising discovery that the C57BL/6J × FVB/NJ × 129S1 mixed genetic background onto which Ctnnb1 loss of function alleles were maintained is profoundly susceptible to voiding dysfunction. The mixed background mice develop a more rapid T+E2-mediated increase in spontaneous urine spotting, are more impaired in ability to initiate bladder contraction, and develop larger and heavier bladders than T+E2 treated C57BL/6J pure bred mice. To better understand mechanisms, we separately evaluated contributions of T and E2 and found that E2 mediates voiding dysfunction. Our findings that genetic factors serve as modifiers of responsiveness to T and E2 demonstrate the need to control for genetic background in studies of male voiding dysfunction. We also show that genetic factors could control severity of voiding dysfunction. We demonstrate the importance of E2 as a key mediator of voiding impairment, and show that the concentration of E2 in subcutaneous implants determines the severity of voiding dysfunction in mice, demonstrating that the mouse model is tunable, a factor which is important for future pharmacological intervention studies.

A mechanism linking perinatal 2,3,7,8 tetrachlorodibenzo-p-dioxin exposure to lower urinary tract dysfunction in adulthood.

Benign prostatic hyperplasia/lower urinary tract dysfunction (LUTD) affects nearly all men. Symptoms typically present in the fifth or sixth decade and progressively worsen over the remainder of life. Here, we identify a surprising origin of this disease that traces back to the intrauterine environment of the developing male, challenging paradigms about when this disease process begins. We delivered a single dose of a widespread environmental contaminant present in the serum of most Americans [2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), 1 µg/kg], and representative of a broader class of environmental contaminants, to pregnant mice and observed an increase in the abundance of a neurotrophic factor, artemin, in the developing mouse prostate. Artemin is required for noradrenergic axon recruitment across multiple tissues, and TCDD rapidly increases prostatic noradrenergic axon density in the male fetus. The hyperinnervation persists into adulthood, when it is coupled to autonomic hyperactivity of prostatic smooth muscle and abnormal urinary function, including increased urinary frequency. We offer new evidence that prostate neuroanatomical development is malleable and that intrauterine chemical exposures can permanently reprogram prostate neuromuscular function to cause male LUTD in adulthood.

Preparation of Microcapsules Coating and the Study of Their Bionic Anti-Fouling Performance.

With the increasing demands to better the marine environment, environmentally friendly anti-fouling coatings have attracted attention from society. Adding hydrolyzable microcapsules without toxin to paints is a very useful and safe method to get bionic anti-fouling coatings with a micro-nano surface structure. Based on this trend, a form of environment-friendly microcapsules were prepared through mini-emulsion polymerization. The target microcapsules had a poly(urea-formaldehyde) (PUF) shell and a mixed core of silicone oil and capsaicin. Additionally, the microcapsules were introduced into zinc acrylate resin to obtain bionic anti-fouling coatings with micro-nano morphology. The effects of polyvinyl alcohol (PVA) molecular weight, stirring rate, and temperature on the morphology of the microcapsules were studied by optical microscopy (OM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). It was found that spherical nanoparticles with smooth surfaces were obtained, and the mean diameter was approximately 1.38 µm when the molecular weight of PVA was 77 K, the stirring rate was 600 rpm and the temperature was 55 °C. Fourier-transform infrared spectra (FTIR) results showed that the silicone oil and capsaicin were successfully encapsulated, the core materials of the microcapsules reached 72.37% and the yield of microcapsules was 68.91% by the Soxhlet method. Furthermore, the hydrophobicity, corrosion resistance and anti-fouling performance of the coatings were evaluated by the water contact angle, electrochemical and real-sea tests. The results indicated that the anti-fouling coatings had excellent hydrophobicity and anti-fouling performance due to the micro-nano convex structure and the release of core materials. Encouragingly, the anti-fouling coatings show excellent and long-term anti-fouling performance, which is expected to be widely applied in marine anti-fouling coatings.

Photocatalytic degradation of methylene blue by a cocatalytic PDA/TiO2 electrode produced by photoelectric polymerization.

This study reports a new method for photocatalysts to degrade organic dyes on organic semiconductors. A novel strategy is reported to form TiO2 nanorod (NR)/polydopamine (PDA) electrodes with a photoelectric polymerization strategy for PDA (pep-PDA) to produce cocatalytic electrodes. Amperometric i-t curves and UV-vis diffuse reflectance spectra were recorded and showed that compared with traditional self-polymerization (sp-PDA) and electropolymerization (ep-PDA), TiO2 NR/pep-PDA exhibited an enhanced photocatalytic activity under visible light. As expected, TiO2 NR/pep-PDA showed a significant improvement for the degradation of methylene blue (MB) under visible light, which can be attributed to the strong absorption of PDA in the visible light region and the more complete and uniform coverage of the TiO2 NRs by the pep-PDA film. This study not only proposes a novel and highly efficient way to load PDA on TiO2 NRs but also provides useful insights for the loading of other photocatalysts on organic semiconductors to degrade organic dyes.