Exploration of Novel Meso-C═N-BODIPY-Based AIE Fluorescent Rotors with Large Stokes Shifts for Organelle-Viscosity Imaging.

The research on fluorescent rotors for viscosity has attracted extensive interest to better comprehend the close relationships of microviscosity variations with related diseases. Although scientists have made great efforts, fluorescent probes for cellular viscosity with both aggregation-induced emissions (AIEs) and large Stokes shifts to improve sensing properties have rarely been reported. Herein, we first report four new meso-C═N-substituted BODIPY-based rotors with large Stokes shifts, investigate their viscosity/AIE characteristics, and perform cellular imaging of the viscosity in subcellular organelles. Interestingly, the meso-C═N-phenyl group-substituted probe 6 showed an obvious 594 nm fluorescence enhancement in glycerol and a moderate 650 nm red AIE emission in water. Further, on attaching CF3 to the phenyl group, a similar phenomenon was observed for 7 with red-shifted emissions, attributed to the introduction of a phenyl group, which plays a key role in the red AIE emissions and large Stokes shifts. Comparatively, for phenyl-group-free probes, both the meso-C═N-trifluoroethyl group and thiazole-substituted probes (8 and 9) exhibited good viscosity-responsive properties, while no AIE was observed due to the absence of phenyl groups. For cellular experiments, 6 and 9 showed good lysosomal and mitochondrial targeting properties, respectively, and were further successfully used for imaging viscosity through the preincubation of monensin and lipopolysaccharide (LPS), indicating that C═N polar groups potentially work as rotatable moieties and organelle-targeting groups, and the targeting difference might be ascribed to increased charges of thiazole. Therefore, in this study, we investigated the structural relationships of four meso-C═N BODIPY-based rotors with respect to their viscosity/AIE characteristics, subcellular-targeting ability, and cellular imaging for viscosity, potentially serving as AIE fluorescent probes with large Stokes shifts for subcellular viscosity imaging.

Artificial cavernosa-like tissue based on multibubble Matrigel and a human corpus cavernous fibroblast scaffold.

Ex vivo tissue culture of the human corpus cavernosum (CC) can be used to explore the tissue structural changes and complex signaling networks. At present, artificial CC-like tissues based on acellular or three-dimensional (3D)-printed scaffolds are used to solve the scarcity of primary penis tissue samples. However, inconvenience and high costs limit the wide application of such methods. Here, we describe a simple, fast, and economical method of constructing artificial CC-like tissue. Human CC fibroblasts (FBs), endothelial cells (ECs), and smooth muscle cells (SMCs) were expanded in vitro and mixed with Matrigel in specific proportions. A large number of bubbles were formed in the mixture by vortexing combined with pipette blowing, creating a porous, spongy, and spatial structure. The CC FBs produced a variety of signaling factors, showed multidirectional differentiation potential, and grew in a 3D grid in Matrigel, which is necessary for CC-like tissue to maintain a porous structure as a cell scaffold. Within the CC-like tissue, ECs covered the surface of the lumen, and SMCs were located inside the trabeculae, similar to the structure of the primary CC. Various cell components remained stable for 3 days in vitro, but the EC content decreased on the 7th day. Wingless/integrated (WNT) signaling activation led to lumen atrophy and increased tissue fibrosis in CC-like tissue, inducing the same changes in characteristics as in the primary CC. This study describes a preparation method for human artificial CC-like tissue that may provide an improved experimental platform for exploring the function and structure of the CC and conducting drug screening for erectile dysfunction therapy.

Effect of a Single Light-intensity Walking Session on Sleep Quality of Patients with Bladder Cancer: A Randomized Cross-Over Study.

OBJECTIVES: Exercise has been recommended to enhance sleep. However, there is a paucity of studies investigating the relationships between exercise and sleep problems in patients with bladder cancer. The authors explored the effects of a single bout of light-intensity walking on the sleep quality of patients with bladder cancer who have sleep disorders. DATA SOURCES: A total of 14 patients with bladder cancer with sleep disorders were recruited for this trial. The participants were randomly assigned to the walking or control condition in a cross-over design to explore the effects of a single light-intensity walking session on objectively measured sleep quality. A two-way repeated measures analysis of variance and a nonparametric permutation test were used to examine intervention effects. Twelve participants (85.7%) completed the trial. A significant group × time interaction for sleep latency (P = .023) was identified. The pairwise comparison showed significant results (P = .012) for the difference between the post-test sleep latency and the pre-test. No significant group × time interactions were observed for the remaining seven sleep parameters. Additionally, only the main effects of time on length of awakening and time in bed were significant (P < .001). CONCLUSION: A single bout of light-intensity walking has a positive effect on shortening the sleep latency of patients with bladder cancer who have sleep disorders. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses can encourage patients with bladder cancer to exercise, even light-intensity walking, which may improve sleep quality.

Low XIST expression in Sertoli cells of Klinefelter syndrome patients causes high susceptibility of these cells to an extra X chromosome.

Klinefelter syndrome (KS) is the most common genetic cause of human male infertility. However, the effect of the extra X chromosome on different testicular cell types remains poorly understood. Here, we profiled testicular single-cell transcriptomes from three KS patients and normal karyotype control individuals. Among the different somatic cells, Sertoli cells showed the greatest transcriptome changes in KS patients. Further analysis showed that X-inactive-specific transcript ( XIST ), a key factor that inactivates one X chromosome in female mammals, was widely expressed in each testicular somatic cell type but not in Sertoli cells. The loss of XIST in Sertoli cells leads to an increased level of X chromosome genes, and further disrupts their transcription pattern and cellular function. This phenomenon was not detected in other somatic cells such as Leydig cells and vascular endothelial cells. These results proposed a new mechanism to explain why testicular atrophy in KS patients is heterogeneous with loss of seminiferous tubules but interstitial hyperplasia. Our study provides a theoretical basis for subsequent research and related treatment of KS by identifying Sertoli cell-specific X chromosome inactivation failure.

Clinical features and microsurgical reconstruction of congenital unilateral absence of the vas deferens with obstructive azoospermia: a tertiary care center experience.

Patients with congenital unilateral absence of the vas deferens (CUAVD) manifest diverse symptoms from normospermia to azoospermia. Treatment for CUAVD patients with obstructive azoospermia (OA) is complicated, and there is a lack of relevant reports. In this study, we describe the clinical features and evaluate the treatments and outcomes of CUAVD patients with OA. From December 2015 to December 2020, 33 patients were diagnosed as CUAVD with OA in Shanghai General Hospital (Shanghai, China). Patient information, ultrasound findings, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated. Of 33 patients, 29 patients were retrospectively analyzed. Vasoepididymostomy (VE) or cross VE was performed in 12 patients, the patency rate was 41.7% (5/12), and natural pregnancy was achieved in one of the patients. The other 17 patients underwent testicular sperm extraction as the distal vas deferens (contralateral side) was obstructed. These findings showed that VE or cross VE remains an alternative treatment for CUAVD patients with OA, even with a relatively low rate of patency and natural pregnancy.

Balancing interactions in proline-based receptors for chiral recognition of l-/d-DOPA.

Proline based receptors (1-14) attached with phenylboronic acid and benzaldehyde binding groups at the N-/C- or C-/N-termini of the proline residue were created for chiral recognition of l-/d-DOPA, in an attempt to examine if balancing the two binding events would influence the recognition. By changing the positions of boronic acid and aldehyde groups substituted on the phenyl rings (1-4, 5-8) and the site at which phenylboronic acid and benzaldehyde moieties attached respectively to the N- and C-termini or C- and N-termini of the proline residue (1-4vs.5-8), and by introducing an electron-withdrawing fluorine atom in the phenyl ring of the weaker binder the benzaldehyde moiety (11vs.1, 14vs.5), we were able to show that a better balance of the two binding events does improve the chiral recognition. This finding can only be made with the current version of receptors that were equipped with two different binding groups. Together with the finding that the chiral recognition performance in mixed organic-aqueous solutions is tunable by varying the solvent composition, we have now arrived at a protocol for designing proline based receptors for extended applications in chiral recognition.

Proteomic analysis of oxidative stress response in human umbilical vein endothelial cells (HUVECs): role of heme oxygenase 1 (HMOX1) in hypoxanthine-induced oxidative stress in HUVECs.

BACKGROUND: Erectile dysfunction (ED) is a well-known complication of diabetes, affecting up to 75% of diabetic men. Although the etiology of diabetic ED is multifactorial, endothelial dysfunction is considered to be a pillar of its pathophysiology. Endothelial dysfunction is caused by the harmful effects of high glucose levels and increased oxidative stress on the endothelial cells that comprise the vascular endothelium. The aim of this study was to identify the proteomic changes caused by high glucose-induced oxidative stress and explore the role of heme oxygenase 1 (HMOX1) in it. METHODS: The cellular proteomic response to hypoxanthine-induced oxidative stress in human umbilical vein endothelial cells (HUVECs) was analyzed by isobaric tags for relative and absolute quantitation (iTRAQ) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins (DEPs) were analyzed through Network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Further validation assays was performed to validate the role of HMOX1. RESULTS: The results showed that 66 and 76 DEPs were markedly upregulated and downregulated, respectively, for HUVECs oxidative stress. Among these proteins, we verified eight dysregulated genes by quantitative reverse transcription PCR, including nucleolin (NCL), X-ray repair cross-complementing protein 6 (XRCC6), ubiquinol-cytochrome C reductase binding protein (UQCRB), non-POU domain containing octamer binding (NONO), heme oxygenase 1 (HMOX1), nucleobindin 1 (NUCB1), DEK, and chromatin target of prmt1 (CHTOP). Further, using overexpression and genetic knockdown approaches, we found that HMOX1 was critical for the oxidative stress response in HUVECs. CONCLUSIONS: We found that HMOX1 was closely related to the oxidative stress response induced by hypoxanthine. To the best of our knowledge, this study is the first overview of the responses of HUVECs to oxidative stress. The findings will contribute to analyses of the detailed molecular mechanisms involved in the pathogenesis of endothelial dysfunction and related molecular mechanisms in ED patients.

Is milder psychological stress responsible for more severe erectile dysfunction?

China is a sexually conservative country compared with Western countries. To evaluate the psychological characteristics of Chinese erectile dysfunction (ED) patients, we conducted a cross-sectional study of 153 ED outpatients. Patients were interviewed with the Structured Interview on Erectile Dysfunction (SIEDY) for pathogenic quantification. ED was measured by International Index of Erectile Function (IIEF). Depression and anxiety were evaluated with 9-item Patient Health Questionnaire (PHQ-9) and 7-item Generalised Anxiety Disorder Scale (GAD-7) respectively. Most patients (74.5%) were <40 years old. IIEF-5 were significantly correlated with SIEDY scale 3 (r = .16, p = .040) and GAD-7 (p = .15, p = .033). The SIEDY scale 1 increased with age, but the IIEF-5, SIEDY scale 3, PHQ-9 and GAD-7 decreased with age. A negative correlation was observed between ED and psychological stress, which conflicts with many Western-country studies. Younger patients were characterised by milder ED but more psychological stress, while older patients were characterised by worse ED but less psychological stress. Which may be responsible for the conflicting result. Meanwhile, the much younger age distribution among Chinese ED outpatients may indicate that quite a few older ED patients (≥40 years) in China do not seek outpatient service which should merit more attention.

Chaperone-mediated autophagy substrate proteins in cancer.

All intracellular proteins undergo continuous synthesis and degradation. Chaperone-mediated autophagy (CMA) is necessary to maintain cellular homeostasis through turnover of cytosolic proteins (substrate proteins). This degradation involves a series of substrate proteins including both cancer promoters and suppressors. Since activating or inhibiting CMA pathway to treat cancer is still debated, targeting to the CMA substrate proteins provides a novel direction. We summarize the cancer-associated substrate proteins which are degraded by CMA. Consequently, CMA substrate proteins catalyze the glycolysis which contributes to the Warburg effect in cancer cells. The fact that the degradation of substrate proteins based on the CMA can be altered by posttranslational modifications such as phosphorylation or acetylation. In conclusion, targeting to CMA substrate proteins develops into a new anticancer therapeutic approach.

[Prevalence of Cognitive Impairments and Its Determinants in Rural Elderly in Sichuan Province].

OBJECTIVE: To determine the prevalence of cognitive impairment and its influencing factors in rural elderly in Sichuan Province. METHODS: A multi-stage random sampling method was adopted to select participants in six towns and eighteen administrative villages in Fushun and Lizhou. The cognitive functions of 1 065 rural elderly were assessed. Factors associated with cognitive impairments of the rural elderly were identified. RESULTS: About 39. 9% of the rural elderly had cognitive impairments. Gender, age, marital status, educational attainment, regular physical activities, quality of life and social support were associated with cognitive impairments. CONCLUSION: The prevalence of cognitive impairments in rural elderly in Sichuan is high in comparison with national and international averages. Targeted interventions are needed based on the identified influencing factors.

Salvianolic Acid B Inhibits Aß Generation by Modulating BACE1 Activity in SH-SY5Y-APPsw Cells.

Alzheimer's disease (AD) is a neurodegenerative disease in humans. The accumulation of amyloid-ß (Aß) plays a critical role in the pathogenesis of AD. Previous studies indicated that Salvianolic acid B (SalB) could ameliorate Aß-induced memory impairment. However, whether SalB could influence the generation of Aß is unclear. Here, we show that SalB (25, 50, or 100 µM) reduces the generation of Aß40 and Aß42 in culture media by decreasing the protein expressions of BACE1 and sAPPß in SH-SY5Y-APPsw cells. Meanwhile, SalB increases the levels of ADAM10 and sAPPα in the cells. However, SalB has no impact on the protein expressions of APP and PS1. Moreover, SalB attenuates oxidative stress and inhibits the activity of GSK3ß, which might be related to the suppression of BACE1 expression and amyloidogenesis. Our study suggests that SalB is a promising therapeutic agent for AD by targeting Aß generation.

In situ plasmonic Ag nanoparticle anchored TiO2 nanotube arrays as visible-light-driven photocatalysts for enhanced water splitting.

An ultrasonication-assisted in situ deposition strategy was utilised to uniformly decorate plasmonic Ag nanoparticles on vertically aligned TiO2 nanotube arrays (NTAs) to construct a Ag@TiO2 NTA composite. The Ag nanoparticles act as efficient surface plasmon resonance (SPR) photosensitizers to drive photocatalytic water splitting under visible light irradiation. The Ag nanoparticles were uniformly deposited on the surface and inside the highly oriented TiO2 nanotubes. The visible-light-driven hydrogen production activities of silver nanoparticle anchored TiO2 nanotube array photocatalysts were evaluated using methanol as a sacrificial reagent in water under a 500 W Xe lamp with a UV light cutoff filter (λ ≥ 420 nm). It was found that the hydrogen production rate of the Ag@TiO2 NTAs prepared with ultrasonication-assisted deposition for 5 min was approximately 15 times higher than that of its pristine TiO2 NTAs counterpart. The highly efficient photocatalytic hydrogen evolution is attributed to the SPR effect of Ag for enhanced visible light absorption and boosting the photogenerated electron-hole separation/transfer. This strategy is promising for the design and construction of high efficiency TiO2 based photocatalysts for solar energy conversion.

[Catastrophic Health Expenditure before and after Compensations from the New Rural Cooperative Medical Scheme in Rural Zigong of Sichuan Province].

OBJECTIVES: To estimate catastrophic health expenditure (CHE) of rural families in Zigong, and to determine the main influencing factors of CHE. METHODS: CHE was estimated using indicators such as occurrence and average deviations. The influencing factors of CHE were identified through binary logistic regression. RESULTS: We found 6.37% catastrophic health payment headcount, 1.13% mean catastrophic payment gap, and 17.80% mean positive gap after compensations. Compensations from the new rural cooperative medical scheme (NCMS) led to a reduction of 74.81% catastrophic health payment headcount for hospitalization costs and 48.00% catastrophic health payment headcount for outpatient costs, respectively. The numbers of hospitalizations in a family, presence of patients with chronic diseases, per capita household income, and numbers of family members with a job were found to be predictors of CHE. CONCLUSIONS: Rural families that have patients with chronic diseases are vulnerable to CHE.The government should develop policies to ease the financial burdens of the families with a high accumulated health expenditure over time.

The effect of immediate surgical bipolar plasmakinetic transurethral resection of the prostate on prostatic hyperplasia with acute urinary retention.

In the present study, we evaluated the safety and efficacy of immediate surgical bipolar plasmakinetic transurethral resection of the prostate (PK-TURP) for patients with benign prostatic hyperplasia (BPH) with acute urinary retention (AUR). We conducted a retrospective analysis of clinical data of BPH patients who received PK-TURP. A total of 1126 BPH patients were divided into AUR (n = 348) and non-AUR groups (n = 778). After the urethral catheters were removed, the urine white blood cell (WBC) count in the AUR group significantly increased compared with the non-AUR group (P < 0.01). However, there was no significant difference in international prostate symptom score, painful urination, and maximal urinary flow rate. The duration of hospitalization of the AUR group was longer than that of the non-AUR group (P < 0.001). A total of 87.1% (303/348) patients in the AUR group and 84.1% (654/778) patients in the non-AUR group completed all of the postoperative follow-up visits. The incidence of urinary tract infection in the AUR group within 3 months after surgery was significantly higher than that in the non-AUR group (P < 0.01). The incidence of temporary urinary incontinence in the AUR group did not exhibit significant difference. During 3-12 months after surgery, there were no significant differences in major complications between the two groups. Multivariate regression analyses showed that age, postvoid residual, maximal urinary flow rate, diabetes, and hypertension, but not the presence of AUR, were independent predictors of IPSS post-PK-TURP. In conclusion, immediate PK-TURP surgery on patients accompanied by AUR was safe and effective.

[Causes of orchiectomy: An analysis of 291 cases].

OBJECTIVE: To study the causes of orchiectomy in different age groups. METHODS: We retrospectively reviewed the clinical data about 291 cases of orchiectomy performed between March 1993 and October 2014 and analyzed the causes of surgery and their distribution in different age groups. RESULTS: The main causes of orchiectomy were testicular torsion (45.8%), cryptorchidism (32.5%) and testicular tumor (16.9%) in the patients aged 0-25 years, testicular tumor (42.4%), cryptorchidism (25.9%) and tuberculosis (10.6%) in those aged 26-50 years. Prostate cancer was the leading cause in those aged 51-75 years (77.6%) or older (84.0%)), and testicular tumor was another cause in the 51-75 years old men (10.2%). Prostate cancer, testicular tumor, cryptorchidism, and testicular torsion were the first four causes of orchiectomy between 1993 and 2009. From 2010 to 2014, however, testicular tumor rose to the top while prostate cancer dropped to the fourth place. CONCLUSION: The causes of orchiectomy vary in different age groups. The proportion of castration for prostate cancer patients significantly reduced in the past five years, which might be attributed to the improvement of comprehensive health care service.

Comparative pharmacokinetics and bile transformation of R-enantiomer and racemic bambuterol after single-dose intravenous, oral administration in rats and beagle dogs.

This study was to compare pharmacokinetics and bile transformation of R-enantiomer bambuterol with its racemate. Pharmacokinetics of R-enantiomer was investigated after single-dose intravenous and three doses of oral administration to rats and beagle dogs. To compare the pharmacokinetics with racemic bambuterol, the same oral doses of racemic bambuterol were also administrated; the blood and bile samples were collected by cannulation. A validated LC-MS/MS method was used to assess the level of bambuterol in plasma and bile. After single intravenous administration, no significant differences were observed between the two drugs in pharmacokinetic data. After oral dosing of R-bambuterol, the AUCs of R-enantiomer presented linear correlation. After same oral dosing of R-enantiomer and its racemate, all the pharmacokinetic parameters were equivalent. However, the clearance and apparent distribution had different results due to species and administration route difference. The bile transformation of these two compounds was similar and implicated that liver transformation accounted for the major metabolism of them. The bioavailability of R-enantiomer and racemate were comparative and relatively high in beagle dogs. Thus, R-enantiomer had a comparative pharmacokinetic profile and bile transformation with racemic bambuterol in rats and beagle dogs. These findings provided references for further clinical study.

Comparison of transurethral plasmakinetic and transvesical prostatectomy in treatment of 100-149 mL benign prostatic hyperplasia.

OBJECTIVE: To compare the safety and efficacy of transurethral plasmakinetic resection of the prostate (PKRP) versus transvesical prostatectomy (TVP) in the treatment of large-volume benign prostatic hyperplasia (LV-BPH) (100-149 mL). METHODS: Ninety-nine BPH patients who had a prostate volume of 100-149 mL were divided into two groups to undergo PKRP or TVP. Preoperative clinical data were analyzed. Patients had follow-up appointments at 1 month, 3 months, 6 months, and 12 months postoperatively. Outcome measures included the International Prostate Symptom Score, quality of life score, maximum urinary flow rate, and postvoid residual urine volume. Adverse effects were also recorded. RESULTS: A total of 96 patients completed the 12-month follow-up. The operative time was longer, but intraoperative blood loss was lower in the PKRP group. Despite a higher percentage of patients requiring a blood transfusion, there was an obvious advantage in gland removal rate in the TVP group. The duration of postoperative catheterization, bladder irrigation, and hospital stay was significantly shorter in the PKRP group. Outcome measures were significantly improved in both groups 1 month postoperatively. The improvement in lower urinary tract symptoms was maintained throughout the 12 months after surgery. There were no significant differences in International Prostate Symptom Score, quality of life, maximum urinary flow rate, and postvoid residual urine volume between the two groups. CONCLUSION: PKRP has the advantage over TVP of being minimally invasive in the treatment of LV-BPH while achieving the same postoperative outcomes.

Bioinspired TiO2 nanostructure films with special wettability and adhesion for droplets manipulation and patterning.

Patterned surfaces with special wettability and adhesion (sliding, sticky or patterned superoleophobic surface) can be found on many living creatures. They offer a versatile platform for microfluidic management and other biological functions. Inspired by their precise arrangement of structure and chemical component, we described a facile one-step approach to construct large scale pinecone-like anatase TiO2 particles (ATP) film. The as-prepared ATP film exhibits excellent superamphiphilic property in air, changes to underwater superoleophobicity with good dynamical stability. In addition, erasable and rewritable patterned superamphiphobic ATP films or three-dimensional (3D) Janus surfaces were constructed for a versatile platform for microfluidic management and biomedical applications. In a proof-of-concept study, robust super-antiwetting feet for artificial anti-oil strider at the oil/water interface, novel superamphiphobic surface for repeatable oil/water separation, and multifunctional patterned superamphiphobic ATP template for cell, fluorecent probe and inorganic nanoparticles site-selective immobilization were demonstrated.

[Low-dose tadalafil for erectile dysfunction following pelvic fracture-induced urethral injury: clinical observation of 42 cases].

OBJECTIVE: To evaluate the efficacy of daily low-dose tadalafil in the treatment of erectile dysfunction (ED) following pelvic fracture-induced urethral injury (PFUI). METHODS: Based on the length of time between pelvic fracture and the patients' clinic visit, we divided 42 PFUI-caused ED patients into groups A (< 1 month), B (6-24 months) and C (> 24 months). We treated them with tadalafil at 5 mg daily for 12 weeks consecutively, followed by evaluation of the therapeutic effect using IIEF-5 questionnaire and Sexual Encounter Profile (SEP) diaries. RESULTS: Thirty-four patients (83.3%) completed the investigation and all responded well to tadalafil medication. Group A showed significant differences from B and C in the increase of IIEF-5 scores and the positive rate of SEP. CONCLUSION: Daily low-dose tadalafil helps penile rehabilitation in ED patients following PFUI, and the earlier the medication is initiated, the better the effect will be.