Extremely Stable Perylene Bisimide-Bridged Regioisomeric Diradicals and Their Redox Properties.

Excellent stability is an essential premise for organic diradicals to be used in organic electronic and spintronic devices. We have attached two tris(2,4,6-trichlorophenyl)methyl (TTM) radical building blocks to the two sides of perylene bisimide (PBI) bridges and obtained two regioisomeric diradicals (1,6-TTM-PBI and 1,7-TTM-PBI). Both of the isomers show super stability rather than the monomeric TTM under ambient conditions, due to the increased conjugation and the electron-withdrawing effects of the PBI bridges. The diradicals show distinct and reversible multistep redox processes, and a spectro-electrochemistry investigation revealed the generation of organic mixed-valence (MV) species during reduction processes. The two diradicals have singlet ground states, very small singlet-triplet energy gaps (ΔES-T ) and a pure open-shell character (with diradical character y0 =0.966 for 1,6-TTM-PBI and 0.967 for 1,7-TTM-PBI). This work opens a window to developing very stable diradicals and offers the opportunity of their further application in optical, electronic and magnetic devices.

Examining the causal association between psoriasis and bladder cancer: A two-sample Mendelian randomization analysis.

BACKGROUND: Previous epidemiological observational studies have potentially associated psoriasis with bladder cancer, but the results are inconsistent, and the causality remains unknown. The present study aimed to examine whether there are causal associations between psoriasis and bladder cancer using bidirectional two-sample Mendelian randomization (MR) analysis. MATERIALS AND METHODS: A two-sample MR analysis was conducted using publicly available genome-wide association study (GWAS) data for individuals diagnosed with psoriasis and bladder cancer. The inverse variance weighted (IVW) method was the primary method. The complementary methods used included the weighted median, MR-Egger, weighted mode, and simple mode methods. Heterogeneity and pleiotropy of the MR results were detected. Moreover, leave-one-out sensitivity analysis was also employed to evaluate the robustness and validity of the findings. RESULTS: No significant causal association was detected between psoriasis incidence and the risk of bladder cancer using the IVW method (OR = 0.999, 95% CI 0.977-1.022; P = 0.956). Similarly, the IVW model revealed no evidence of a causal relationship between bladder cancer and the risk of psoriasis (OR = 0.979, 95%CI = 0.873-1.098; P = 0.716). The results of the complementary methods were consistent with those of the IVW method. There was no notable horizontal pleiotropy or heterogeneity (P > 0.05) in our MR analysis. The results of sensitivity analysis confirmed that the MR estimates were not driven by single-nucleotide polymorphisms (SNPs). CONCLUSION: This study does not support a causal relationship between psoriasis and bladder cancer.

Identification and transcriptional response of ATP-binding cassette transporters to beta-cypermethrin in the poultry red mite, Dermanyssus gallinae.

Dermanyssus gallinae, a worldwide pest in birds, has developed varying degrees of resistance to insecticides. The ATP-binding cassette (ABC) transporters are essential for the removal of xenobiotics from arthropods. However, our knowledge about ABC transporter proteins in D. gallinae is limited. Forty ABC transporters were identified in the transcriptome and genome of D. gallinae. The resistant population displayed an augmented metabolic rate for beta-cypermethrin compared to the susceptible group, with a remarkable increase in the content of ABC transporters. Verapamil was found able to increase the toxicity of beta-cypermethrin in the resistant population. Results from qRT-PCR analysis showed that eleven ABC transcripts were more highly expressed in the resistant population than the susceptible group at all stages of development, and beta-cypermethrin was observed to be able to induce the expression of DgABCA5, DgABCB4, DgABCD3, DgABCE1 and DgABCG5 in D. gallinae. RNAi-mediated knockdown of the five genes was observed to increase the susceptibility of resistant mites to beta-cypermethrin. These results suggest that ABC transporters, DgABCA5, DgABCB4, DgABCD3, DgABCE1 and DgABCG5 genes, may be related to beta-cypermethrin resistance in D. gallinae. This research will serve as a foundation for further studies on mechanism of insecticide resistance, which could be beneficial for controlling D. gallinae.

Spindle pole body component 24 homolog potentiates tumor progression via regulation of SRY-box transcription factor 2 in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common pathological subtype of human kidney cancer with a high probability of metastasis. To understand the molecular processing essential for ccRCC tumorigenicity, we conducted an integrative in silico analysis of The Cancer Genome Atlas (TCGA) ccRCC dataset and clustered randomly interspersed short palindromic repeats (CRISPR) screening dataset of ccRCC cell lines from Depmap. We identified spindle pole body component 24 homolog (SPC24) as an essential gene for ccRCC cell lines with prognostic significance in the TCGA database. Targeting SPC24 by CRISPR/Cas9-mediated gene knockout attenuated ccRCC proliferation, metastasis, and in vivo tumor growth. Furthermore, we found that SPC24 regulates metastasis genes expression in a SRY-box transcription factor 2 (SOX2)-dependent manner. The anti-proliferative effects of SPC24 knockout were strengthened with SOX2 knockdown. Collectively, our findings suggest SPC24 has a pivotal function in promoting ccRCC progression, providing a new insight for the treatment of ccRCC.

A novel cuproptosis-related prognostic gene signature in adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is an aggressive and rare malignant tumor associated with poor outcomes. Cuproptosis, a new pattern of cell death, relies on mitochondrial respiration and is associated with protein lipoylation. Increasing evidence has demonstrated the potential roles of cuproptosis in several tumor entities. However, the relationship between cuproptosis and ACC remains unclear. METHODS: In total, 10 cuproptosis-related genes (CRGs) of patients with ACC were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases and differential expression analysis of CRGs was analyzed. Functional enrichment of the CRGs was performed and protein-protein interaction analysis was utilized to explore the association between the CRGs. Cuproptosis-related risk score (CRRS) was constructed by Lasso Cox regression and validated. RESULTS: In the current study, the alteration and expression patterns of 10 CRGs in TCGA-ACC datasets were analyzed. We identified different expression patterns of CRGs in ACCs, discovered strong associations between CRGs and ACCs, and found that the CRGs were associated with immune infiltration in ACCs. A CRRS was created thereafter to predict overall survival (OS). CRRS = (0.083103718) *FDX1 + (-0.278423862) *LIAS+(0.090985682) *DLAT+(-0.018784047) *PDHA1 + (0.297218951) *MTF1 + (0.310197964) *CDKN2A. Patients were divided into high- and low-risk groups based on their CRRS, and independent prognostic factors were investigated. Finally, CDKN2A and FDX1 were found to be independent prognostic predictors of patients with ACC. CONCLUSIONS: CDKN2A and FDX1 are independent prognostic predictors of patients with ACC. Cuproptosis may play a role in the development of ACC, providing a new perspective on therapeutic strategies related to CRGs for cancer prevention and treatment.

Molten Salt Shielded Synthesis of Monodisperse Layered CaZnOS-Based Semiconductors for Piezophotonic and X-Ray Detection Applications.

CaZnOS-based semiconductors are the only series of material system discovered that can simultaneously realize a large number of dopant elements to directly fulfill the highly efficient full-spectrum functionality from ultraviolet to near-infrared under the same force/pressure. Nevertheless, owing to the high agglomeration of the high temperature solid phase manufacturing process, which is unable to control the crystal morphology, the application progress is limited. Here, the authors report first that CaZnOS-based fine monodisperse semiconductor crystals with various doping ions are successfully synthesized by a molten salt shielded method in an air environment. This method does not require inert gas ventilation, and therefore can greatly reduce the synthesis cost and more importantly improve the fine control of the crystal morphology, along with the crystals' dispersibility and stability. These doped semiconductors can not only realize different colors of mechanical-to-optical energy conversion, but also can achieve multicolor luminescence under low-dose X-ray irradiation, moreover their intensities are comparable to the commercial NaI:Tl. They can pave the way to the new fields of advanced optoelectronic applications, such as piezophotonic systems, mechanical energy conversion and harvesting devices, intelligent sensors, and artificial skin as well as X-ray applications.

A new method using quail (Coturnix coturnix) as a suitable host for laboratory rearing of Dermanyssus gallinae.

The poultry red mite (PRM) is a detrimental blood-feeding ectoparasite infesting poultry and sylvatic birds. A traditional rearing system of PRMs was usually established by using chickens as the host. However, the system with chickens had some defects, such as high feed consumption, large amount of feces, high cost, and intensive labor. In present study, we used quails as the host to rear mites, and compared the reproductive efficiency of this new system with that of the chicken system. The results showed that the number of mites increased 96-fold and the number of eggs increased 50-fold after four weeks in the quail system, which were significantly higher than those in the system with chickens. The survival rates of mites in both systems were higher than 95%, and the value in the quail system at the fourth week was significantly better than that of the chicken system. The statistical results of feed consumption, live weight, and daily excrement of chickens and quails showed that the quail system was more stable with less feed consumption and less waste excretion than the chicken system. Comparing the number of eggs laid by each female mite, hatching rates and molting rates in both systems, we can conclude that the breeding system, in which quails replaced chickens as hosts, had no effect on the fecundity of D. gallinae. In conclusion, the new system established using quails as the host, is a highly efficient alternative for largely rearing of mites under laboratory conditions.

Construction of Glucose-6-Phosphate Dehydrogenase Overexpression Strain of Schizochytrium sp. H016 to Improve Docosahexaenoic Acid Production.

Docosahexaenoic acid (DHA) is an important omega-3 polyunsaturated fatty acid (PUFA) that plays a critical physiological role in human health. Schizochytrium sp. is considered an excellent strain for DHA production, but the synthesis of DHA is limited by the availability of nicotinamide adenine dinucleotide phosphate (NADPH). In this study, the endogenous glucose-6-phosphate dehydrogenase (G6PD) gene was overexpressed in Schizochytrium sp. H016. Results demonstrated that G6PD overexpression increased the availability of NADPH, which ultimately altered the fatty acid profile, resulting in a 1.91-fold increase in DHA yield (8.81 g/L) and increased carbon flux by shifting it from carbohydrate and protein synthesis to lipid production. Thus, G6PD played a vital role in primary metabolism. In addition, G6PD significantly increased DHA content and lipid accumulation by 31.47% and 40.29%, respectively. The fed-batch fermentation experiment results showed that DHA production reached 17.01 g/L in the overexpressing G6PD strain. These results elucidated the beneficial effects of NADPH on the synthesis of PUFA in Schizochytrium sp. H016, which may be a potential target for metabolic engineering. Furthermore, this study provides a promising regulatory strategy for the large-scale production of DHA in Schizochytrium sp.

Extreme material parameters accessible by active acoustic metamaterials with Willis coupling.

Active acoustic metamaterials incorporate electric circuit elements that input energy into an otherwise passive medium to aptly modulate the effective material properties. Here, we propose an active acoustic metamaterial with Willis coupling to drastically extend the tunability of the effective density and bulk modulus with the accessible parameter range enlarged by at least two orders of magnitude compared to that of a non-Willis metamaterial. Traditional active metamaterial designs are based on local resonances without considering the Willis coupling that limit their accessible effective material parameter range. Our design adopts a unit cell structure with two sensor-transducer pairs coupling the acoustic response on both sides of the metamaterial by detecting incident waves and driving active signals asymmetrically superimposed onto the passive response of the material. The Willis coupling results from feedback control circuits with unequal gains. These asymmetric feedback control circuits use Willis coupling to expand the accessible range of the effective density and bulk modulus of the metamaterial. The extreme effective material parameters realizable by the metamaterials will remarkably broaden their applications in biomedical imaging, noise control, and transformation acoustics-based cloaking.

Electrochemical Synthesis, Deposition, and Doping of Polycyclic Aromatic Hydrocarbon Films.

Polycyclic aromatic hydrocarbons (PAHs) are employed as organic semiconductors because their delocalized π-electron systems and strong intermolecular interactions endow them with an exceptional charge-transport ability. However, the deposition of PAHs from solution onto high-quality thin films is often difficult. Here, we report a one-step electrochemical method to synthesize and deposit unsubstituted PAHs, starting from twisted oligophenyl precursors. The cyclodehydrogenated products were analyzed by matrix-assisted laser-desorption time-of-flight mass spectrometry as well as Fourier transform infrared and Raman spectroscopy. With this electrosynthesis and deposition, the PAHs stack into compact and ordered supramolecular structures along the π-π direction to form thin films with controllable thicknesses and doping levels. The direct fabrication of PAH films opens new pathways toward PAH-based optoelectronic devices.

An explainable supervised machine learning predictor of acute kidney injury after adult deceased donor liver transplantation.

BACKGROUND: Early prediction of acute kidney injury (AKI) after liver transplantation (LT) facilitates timely recognition and intervention. We aimed to build a risk predictor of post-LT AKI via supervised machine learning and visualize the mechanism driving within to assist clinical decision-making. METHODS: Data of 894 cases that underwent liver transplantation from January 2015 to September 2019 were collected, covering demographics, donor characteristics, etiology, peri-operative laboratory results, co-morbidities and medications. The primary outcome was new-onset AKI after LT according to Kidney Disease Improving Global Outcomes guidelines. Predicting performance of five classifiers including logistic regression, support vector machine, random forest, gradient boosting machine (GBM) and adaptive boosting were respectively evaluated by the area under the receiver-operating characteristic curve (AUC), accuracy, F1-score, sensitivity and specificity. Model with the best performance was validated in an independent dataset involving 195 adult LT cases from October 2019 to March 2021. SHapley Additive exPlanations (SHAP) method was applied to evaluate feature importance and explain the predictions made by ML algorithms. RESULTS: 430 AKI cases (55.1%) were diagnosed out of 780 included cases. The GBM model achieved the highest AUC (0.76, CI 0.70 to 0.82), F1-score (0.73, CI 0.66 to 0.79) and sensitivity (0.74, CI 0.66 to 0.8) in the internal validation set, and a comparable AUC (0.75, CI 0.67 to 0.81) in the external validation set. High preoperative indirect bilirubin, low intraoperative urine output, long anesthesia time, low preoperative platelets, and graft steatosis graded NASH CRN 1 and above were revealed by SHAP method the top 5 important variables contributing to the diagnosis of post-LT AKI made by GBM model. CONCLUSIONS: Our GBM-based predictor of post-LT AKI provides a highly interoperable tool across institutions to assist decision-making after LT.

Development and performance assessment of novel machine learning models to predict pneumonia after liver transplantation.

BACKGROUND: Pneumonia is the most frequently encountered postoperative pulmonary complications (PPC) after orthotopic liver transplantation (OLT), which cause high morbidity and mortality rates. We aimed to develop a model to predict postoperative pneumonia in OLT patients using machine learning (ML) methods. METHODS: Data of 786 adult patients underwent OLT at the Third Affiliated Hospital of Sun Yat-sen University from January 2015 to September 2019 was retrospectively extracted from electronic medical records and randomly subdivided into a training set and a testing set. With the training set, six ML models including logistic regression (LR), support vector machine (SVM), random forest (RF), adaptive boosting (AdaBoost), extreme gradient boosting (XGBoost) and gradient boosting machine (GBM) were developed. These models were assessed by the area under curve (AUC) of receiver operating characteristic on the testing set. The related risk factors and outcomes of pneumonia were also probed based on the chosen model. RESULTS: 591 OLT patients were eventually included and 253 (42.81%) were diagnosed with postoperative pneumonia, which was associated with increased postoperative hospitalization and mortality (P < 0.05). Among the six ML models, XGBoost model performed best. The AUC of XGBoost model on the testing set was 0.734 (sensitivity: 52.6%; specificity: 77.5%). Pneumonia was notably associated with 14 items features: INR, HCT, PLT, ALB, ALT, FIB, WBC, PT, serum Na+, TBIL, anesthesia time, preoperative length of stay, total fluid transfusion and operation time. CONCLUSION: Our study firstly demonstrated that the XGBoost model with 14 common variables might predict postoperative pneumonia in OLT patients.

Effect of urban air pollution on CRP and coagulation: a study on inpatients with acute exacerbation of chronic obstructive pulmonary disease.

PURPOSE: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an important event in the course of chronic obstructive pulmonary disease that negatively affects patients' quality of life and leads to higher socioeconomic costs. While previous studies have demonstrated a significant association between urban air pollution and hospitalization for AECOPD, there is a lack of research on the impact of particulate matter (PM) on inflammation and coagulation in AECOPD inpatients. Therefore, this study investigated the association of changes in coagulation function and C-reactive protein (CRP) with PM levels in the days preceding hospitalization. PATIENTS AND METHODS: We reviewed the medical records of AECOPD patients admitted to Putuo Hospital, Shanghai University of Traditional Chinese Medicine, between March 2017 and September 2019. We analyzed the association of coagulation function and CRP level in AECOPD patients with PM levels in the days before hospitalization. Multivariate unconditional logistic regression analyses were used to evaluate the adjusted odds ratio (OR) and 95% confidence interval (CI) for the association of CRP data with hospitalization day. Kruskal-Wallis tests were used to evaluate mean aerodynamic diameter of ≥ 2.5 µm (PM2.5) exposure on the day before hospitalization; we assessed its association with changes in prothrombin time (PT) in AECOPD inpatients with different Global Initiative for Chronic Obstructive Lung Disease (GOLD) classes. RESULTS: The peripheral blood PT of AECOPD patients with PM2.5 ≥ 25 mg/L on the day before hospitalization were lower than those of patients with PM2.5 < 25 mg/L (t = 2.052, p = 0.041). Patients with severe GOLD class exposed to greater than 25 mg/L of PM2.5on the day before hospitalization showed significant differences in PT (F = 9.683, p = 0.008). Peripheral blood CRP levels of AECOPD patients exposed to PM2.5 ≥ 25 mg/L and PM10 ≥ 50 mg/L on the day before hospitalization were higher than those of patients exposed to PM2.5 < 25 mg/L and PM10 < 50 mg/L (t = 2.008, p = 0.046; t = 2.637, p = 0.009). Exposure to < 25 mg/L of PM2.5 on the day before hospitalization was significantly associated with CRP levels (adjusted OR 1.91; 95% CI 1.101, 3.315; p = 0.024). CONCLUSION: Exposure of patients with AECOPD to high PM levels on the day before hospitalization was associated with an increased CRP level and shortened PT. Moreover, PM2.5 had a greater effect on CRP level and PT than mean aerodynamic diameter of ≥ 10 µm (PM10). AECOPD patients with severe GOLD class were more sensitive to PM2.5-induced shortening of PT than those with other GOLD classes.

Delayed Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates Impaired Penile Hemodynamics in Rats Subjected to Pelvic Neurovascular Injury.

BACKGROUND: Erectile dysfunction (ED) caused by pelvic neurovascular injury (PNVI) is often refractory to treatment. In many cases, erectogenic therapy is administered in a delayed fashion. AIM: To evaluate penile hemodynamic effects and histologic changes associated with delayed low-intensity extracorporeal shock wave therapy (Li-ESWT) after PNVI ED in a rat model. We visualized images using immunofluorescence and 3-dimensional imaging of solvent-cleared organs (3DISCO), a novel imaging technique. METHODS: A total of 32 Sprague-Dawley male rats aged 12 weeks were divided equally into 4 groups: sham surgery as normal controls (NC), PNVI controls (PC), PNVI with very-low-energy Li-ESWT (PVL), and PNVI with low-energy Li-ESWT (PL). Bilateral cavernous nerve crush and internal pudendal bundle ligation were performed in the 3 PNVI groups. Li-ESWT was administered twice a week for 4 weeks in the PL and PVL groups starting at 4 weeks after PNVI. OUTCOMES: Intracavernous pressure (ICP) studies (normalized to mean arterial pressure [MAP]) were conducted in all subject animals. After testing, tissue was harvested for immunofluorescence staining and 3DISCO analysis. RESULTS: Mean ICP/MAP was lower in PC animals compared with NC animals (0.37 ± 0.03 vs 0.91 ± 0.03, respectively; P = .001). The ICP/MAP ratio was significantly higher in PVL and PL animals (0.66 ± 0.07 and 0.82 ± 0.05, respectively) compared with PC animals (P = .002 and .001, respectively). Detailed microstructures and trajectories of nerves and vessels were identified with immunofluorescence and 3DISCO. The PC group had lower density of nerves, axons, neuronal nitric oxide synthase-positive nerves, and Schwann cells in the dorsal penis. Animals in the PL group had significantly higher expression of all of these markers compared with PC animals. CLINICAL IMPLICATIONS: Li-EWST may have utility in the management of severe ED related to PNVI from severe pelvic injury or radical pelvic surgeries, even when administered in a delayed fashion. STRENGTH & LIMITATIONS: This study of a severe ED phenotype involved treatment administered in a delayed fashion, which is more consistent with how therapy likely would be delivered in a real-world clinical context. Moreover, because the treatment commenced at 4 weeks after injury, when nerve and tissue atrophy have already occurred, the results imply that Li-ESWT can be used for regenerative therapy. Additional studies on dose optimization and treatment interval are needed to inform the design of human clinical trials. CONCLUSION: Li-ESWT ameliorates the negative functional and histologic effects of severe pelvic neurovascular injury in a rat model system. 3DISCO provides high-resolution images of neuroanatomy and neural regeneration. Wang HS, Ruan Y, Banie L, et al. Delayed Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates Impaired Penile Hemodynamics in Rats Subjected to Pelvic Neurovascular Injury. J Sex Med 2019;16:17-26.

Strategy for Extending the Nitrogen Chain: The Bis(1,2,3-triazole) Formation Reaction from Tosylhydrazones and N-Amino Azole.

A facile and versatile synthesis strategy for the bis(1,2,3-triazole) formation reaction was developed from tosylhydrazones and N-amino (N-NH2) azole instead of C-amino amine derivatives. The novel energetic compounds containing the bicycle catenated six-nitrogen chain (N6) and the first example of N7 neutral compounds were synthesized in a moderate or high yield. The possible mechanism of bis(1,2,3-triazole) formation reaction based on amino azole of N-NH2 was verified by the X-ray crystal structure of key intermediates. In addition, four energetic compounds 4aa, 4ba, 4ac, and 4ad containing N6 and N7 structures possess acceptable decomposition temperatures (150.1-201.6 °C) and moderate calculated detonation performances (6850-7727 m/s). Among them, 4aa (N6 structure) and 4ad (N7 structure) could be used as the melt-cast explosive candidate and the gas generation agent candidate, respectively. This type of nitrogen-nitrogen bonding formation opens a new method for discovery of novel high-nitrogen energetic compounds containing catenated multiple nitrogen atoms especially odd number nitrogen compounds.

The effects of microenergy acoustic pulses on animal model of obesity-associated stress urinary incontinence. Part 2: In situ activation of pelvic floor and urethral striated muscle progenitor cells.

AIM: To investigate the possibility and mechanism of microenergy acoustic pulses (MAP) for activating tissue resident stem/progenitor cells within pelvic and urethral muscle and possible mechanism. METHODS: The female Zucker Lean and Zucker Fatty rats were randomly divided into four groups: ZL control, ZLMAP, ZF control, and ZFMAP. MAP was applied at 0.033 mJ/mm2 , 3 Hz for 500 pulses, and the urethra and pelvic floor muscles of each rat was then harvested for cell isolation and flow cytometry assay. Freshly isolated cells were analyzed by flow cytometry for Pax-7, Int-7α, H3P, and EdU expression. Meanwhile, pelvic floor muscle-derived stem cells (MDSCs) were harvested through magnetic-activated cell sorting, MAP was then applied to MDSCs to assess the mechanism of stem cell activation. RESULTS: Obesity reduced EdU-label-retaining cells and satellite cells in both pelvic floor muscle and urethra, while MAP activated those cells and enhanced cell proliferation, which promoted regeneration of striated muscle cells of the pelvic floor and urethral sphincter. Activation of focal adhesion kinase (FAK)/AMP-activated protein kinase (AMPK) /Wnt/ß-catenin signaling pathways by MAP is the potential mechanism. CONCLUSIONS: MAP treatment activated tissue resident stem cells within pelvic floor and urethral muscle in situ via activating FAK-AMPK and Wnt/ß-catenin signaling pathway.

The effects of microenergy acoustic pulses on an animal model of obesity-associated stress urinary incontinence. Part 1: Functional and histologic studies.

AIM: Obesity is a strong independent risk factor for urinary incontinence. Effective therapeutic approaches for obesity-associated stress urinary incontinence (OA-SUI) are lacking as the mechanisms remain unclear. The aim of our study is to explore the impacts of microenergy acoustic pulse (MAP) therapy on urethral and pelvic floor muscle structure and function in female lean and fatty rats. METHODS: A total 24 Zucker fatty (ZF) and 24 Zucker lean (ZL) female 24-week-old rats were grouped into four groups: ZL control, ZLMAP, ZF control, and ZFMAP. For MAP treatment, 500 pulses were delivered at an energy level of 0.033 mJ/mm 2 and a frequency of 3 Hz and were applied twice a week for 4 weeks. After a 1-week washout, all rats underwent conscious cystometry and leak-point pressure (LPP) measurements followed by ex vivo organ-bath assay and histological study. RESULTS: ZF rats had lower LPP as compared to ZL rats, and MAP treatment significantly improved LPP in ZF rats (P < .05). Impaired muscle contractile activity (MCA) in organ-bath study was noted in ZF rats. MAP treatment significantly increased MCA in ZF rats (P < .05) and also increased the thickness of the striated muscle layer and the number of neuromuscular junctions (NMJs). In situ, MAP activated muscle satellite cells significantly (P < .05). CONCLUSIONS: Obesity impairs the function of both the urethral sphincter and the pelvic floor and leads to atrophy and distortion of the striated muscle in obese female rats. These issues contribute to OA-SUI. MAP improves continence by stimulating muscle regeneration and nerve innervation as well as by activating satellite cells.

[Effects of phthalate on pulmonary allergy of offspring during intrauterin and lactating exposure].

OBJECTIVE: To investigate the effects of exposure to diethyl phthalate(DEHP) during pregnancy and lactation in respiratory allergy of offspring Wistar rats. METHODS: To establish the maternal DEHP exposure model: 36 healthy 2-month-old female Wistar rats were divided into three different dose groups. From GD0, each group of pregnant mice were given different concentrations of DEHP(0, 30, 300 mg/(kg·d)) until to the newborn weaning(PND21). After birth, one of offspring was selected from each cage in different dose groups. At PND21 and PND28 the offspring were sensitized by intraperitoneal injection(i. p. ) OVA and continuous nasal sensitization at PND32, PND33, PND34. Bronchoalveolar lavage fluid(BALF) and lung tissue were collected at PND35 with non-sensitized groups. ELISA detected the secretion of Th2 cytokine interleukin(IL)-4, IL-5 and IL-13 in BALF, and the pathological changes of allergic inflammation in lung tissues were observed by HE and PAS staining. Expression of epithelium-derived factor IL-33 detected by immunohistochemistry. RESULTS: In BALF, compared with the control group, the total number of inflammatory cells and eosinophils in the DEHP0+OVA group increased to(131. 500±25. 548)×10~4, (32. 000±10. 079)×10~4(P<0. 05); The total number of inflammatory cells and eosinophils in the DEHP30+OVA group increased to(156. 167±17. 994)×10~4, (16. 331±6. 667)×10~4(P<0. 05); and the total number of inflammatory cells and eosinophils in the DEHP300+OVA group increased to(172. 167±19. 994)×10~4, (55. 000±17. 018)×10~4(P<0. 05). After adding different doses of DEHP and OVA, compared with the control group, The expression levels of IL-4, IL-5, IL-13 in DEHP0+OVA group increased to(38. 401±6. 594) pg/mL(P>0. 05), (30. 026±2. 756) pg/mL(P<0. 05), (13. 806±4. 355) pg/mL(P<0. 05); The expression levels of IL-4, IL-5 and IL-13 in DEHP30+OVA group increased to(57. 733±7. 293) pg/mL(P<0. 05) and(31. 544±1. 043) pg/mL(P>0. 05), (18. 068±1. 497) pg/mL(P<0. 05); The expression levels of IL-4, IL-5 and IL-13 in DEHP300+OVA group increased to(54. 943±6. 049) pg/mL(P>0. 05) and(32. 377±3. 739)pg/mL(P>0. 05), (20. 168±0. 939) pg/mL(P<0. 05), respectively. The tissue section of all the DEHP+saline groups could be observed that no obvious allergic inflammatory reaction, meanwhile all the DEHP+OVA groups had a relatively obvious allergic reaction and were severe with the increase of DEHP dose. Immunohistochemistry showed no significant increase in the expression of IL-33 in the DEHP+saline groups, while the expression of IL-33 in the DEHP+OVA groups increased with a certain dose response. CONCLUSION: Exposure to DEHP during pregnancy and lactation will aggravate the sensitization reaction of offspring, the possible mechanism that DEHP increase the Th2 type of immune response may be the overexpression of IL-33 in the epithelial cells.

The effect of low-intensity extracorporeal shockwave therapy in an obesity-associated erectile dysfunction rat model.

OBJECTIVES: To investigate the feasibility of the Zucker fatty (ZF) rat as a model for research in to obesity-associated erectile dysfunction (OAED) and to determine the effect of low-intensity extracorporeal shockwave therapy (Li-ESWT) on penile tissue and function in these rats. MATERIALS AND METHODS: Eight new-born male Zucker lean (ZL group) rats (ZUC-Leprfa 186) and 16 new-born male ZF rats (ZUC-Leprfa 185) were injected with 5-ethynyl-2'-deoxyuridine (EdU) at birth to identify and monitor endogenous stem cells. Insulin tolerance testing was performed at 10 weeks of age. Beginning at 12 weeks of age, eight ZF rats were kept as controls, and the remaining eight ZF rats were treated with Li-ESWT (0.02 mJ/mm2 , 3 Hz, 500 pulses; ZF + SW group) twice a week for 4 weeks. Following a 1-week washout period, erectile function was evaluated by measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP). Penile tissues were then harvested for histological study to assess smooth muscle/collagen content and endothelium content in the corpora cavernosum. LipidTOX™ staining was used to evaluate lipid accumulation. EdU, as a marker of cell activation, and phosphorylated histone 3 (H3P), as a marker of cell mitosis, were also assessed. RESULTS: The ICP/MAP indicated that erectile function was severely impaired in the ZF group as compared with the ZL group. In the ZF + SW group, erectile function was significantly improved (P < 0.05). Muscle atrophy was seen in the ZF group, while Li-ESWT increased the muscle content in ZF + SW group. Moreover, the penile endothelium was damaged in the ZF group, and Li-ESWT enhanced the regeneration of endothelial cells (P < 0.01) in the ZF + SW group. Lipid accumulation was seen in the penile tissue of ZF rats. Li-ESWT significantly reduced both the amount and the distribution pattern of LipidTOX, suggesting decreased overall lipid infiltration. Furthermore, Li-ESWT increased EdU-positive cells and markedly enhanced the phosphorylation level of H3P at Ser-10 in the ZF + SW group. Most H3P-positive cells were located within smooth muscle cells, with some located in the endothelium suggesting that these tissues are the reservoirs of penile stem/progenitor cells. CONCLUSION: ZF rats can serve as an animal model in which to study OAED. This study reveals that obesity impairs erectile function by causing smooth muscle atrophy, endothelial dysfunction, and lipid accumulation in the corpus cavernosum. Li-ESWT restored penile haemodynamic parameters in the ZF rats by restoring smooth muscle and endothelium content and reducing lipid accumulation. The underlying mechanism of Li-ESWT appears to be activation of stem/progenitor cells, which prompts cellular proliferation and accelerates penile tissue regeneration. Our findings are of interest, not just as a validation of this emerging treatment for erectile dysfunction, but also as a novel and potentially significant method to modulate endogenous stem/progenitor cells in other disease processes.

Low-intensity extracorporeal shockwave therapy ameliorates diabetic underactive bladder in streptozotocin-induced diabetic rats.

OBJECTIVES: To evaluate the therapeutic effect of once-weekly low-intensity extracorporeal shock wave therapy (Li-ESWT) on underactive bladder (UAB) in the streptozotocin (STZ)-induced diabetic rat model. MATERIALS AND METHODS: In all, 36 female Sprague-Dawley rats were divided into three groups: normal control (NC), diabetes mellitus control (DMC), and DM with Li-ESWT (DM Li-ESWT). The two DM groups received an intraperitoneal 60 mg/kg STZ injection to induce DM. The Li-ESWT was applied toward the pelvis of the rats starting 4 weeks after STZ administration and lasting for 4 weeks. The Li-ESWT was given once weekly, with an energy flux density of 0.02 mJ/mm2 at 3 Hz for 400 pulses. All rats underwent conscious cystometry, leak-point pressure (LPP) assessment, ex vivo organ-bath study, histology, immunofluorescence, and Western Blot analysis. RESULTS: Conscious cystometry revealed voiding dysfunction in the DMC group, whereas the DM Li-ESWT group showed significantly improved voiding function, reflected in a reduced post-void residual urine volume and increased LPP compared to the DMC group. Ex vivo organ-bath studies showed that Li-ESWT enhanced muscle contractile activity of the bladder and urethra during electrical-field stimulation and drug stimulation. Histologically, Li-ESWT significantly restored bladder morphology, reflected by a reduction in the intravesical lumen area and increased muscle proportion of the bladder wall. Western Blot analysis showed higher smooth muscle actin expression in the bladder wall in the DM Li-ESWT group compared to the DMC group. Immunofluorescence showed decreased nerve-ending distribution, and destroyed and shortened nerve fibres in the DMC group, and recovery of neuronal integrity and innervation in the DM Li-ESWT group. CONCLUSIONS: In conclusion, Li-ESWT ameliorated UAB and urinary incontinence in the diabetic UAB rat model. The improvement appears to be the result of restoration of bladder and urethral structure and function by Li-ESWT. Li-ESWT is non-invasive and may become a better alternative therapy for UAB. Further investigations are warranted.