Genetic prediction of modifiable lifestyle factors for erectile dysfunction.

Background: The causal relationship between certain lifestyle factors and erectile dysfunction (ED) is still uncertain. Aim: The study sought to investigate the causal effect of 9 life factors on ED through 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR). Methods: Genetic instruments to proxy 9 risk factors were identified by genome-wide association studies. The genome-wide association studies estimated the connection of these genetic variants with ED risk (n = 223 805). We conducted SVMR, inverse variance-weighting, Cochran's Q, weighted median, MR-Egger, MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier), and MVMR analyses to explore the total and direct relationship between life factors and ED. Outcomes: The primary outcome was defined as self or physician-reported ED, or using oral ED medication, or a history of surgery related to ED. Results: In SVMR analyses, suggestive associations with increased the risk of ED were noted for ever smoked (odds ratio [OR], 5.894; 95% confidence interval [CI], 0.469 to 3.079; P = .008), alcohol consumption (OR, 1.495; 95% CI, 0.044 to 0.760; P = .028) and body mass index (BMI) (OR, 1.177; 95% CI, 0.057 to 0.268; P = .003). Earlier age at first intercourse was significantly related to reduced ED risk (OR, 0.659; 95% CI, -0.592 to -0.244; P = 2.5 × 10-6). No strong evidence was found for the effect of coffee intake, time spent driving, physical activity, and leisure sedentary behaviors on the incidence of ED (All P > .05). The result of MVMR analysis for BMI (OR, 1.13; 95% CI, 1.01 to 1.25; P = .045) and earlier age at first intercourse (OR, 0.77; 95% CI, 0.56 to 0.99; P = .018) provided suggestive evidence for the direct impact on ED, while no causal factor was detected for alcoholic drinks per week and ever smoked. Clinical implications: This study provides evidence for the impact of certain modifiable lifestyle factors on the development of ED. Strengths and limitations: We performed both SVMR and MVMR to strengthen the causal relationship between exposures and outcomes. However, the population in this study was limited to European ancestry. Conclusion: Ever smoked, alcoholic drinks per week, BMI, and age first had sexual intercourse were causally related to ED, while the potential connection between coffee intake, physical activity, recreational sedentary habits, and increased risk of ED needs to be further confirmed.

Ammonia-Induced Anomalous Ion Transport in Covalent Organic Framework Nanochannels.

More anomalous transport behaviors have been observed with the rapid progress in nanofabrication technology and characterization tools. The ions/molecules inside nanochannels can act dramatically different from those in the bulk systems and exhibit novel mechanisms. Here, we have reported the fabrication of a nanodevice, covalent organic frameworks covered theta pipette (CTP), that combine the advantages of theta pipette (TP), nanochannels framework, and field-effect transistors (FETs) for controlling and modulating the anomalous transport. Our results show that ammonia, a weak base, causes a continuous supply of ions inside covalent organic framework (COF) nanochannels, leading to an abnormally high current depending on the ionic/molecular size and the pore size of the nanochannel. Furthermore, CTP can distinguish different concentrations of ammonia and have all of the qualities of a nanosensor.

Study on Ammonia Content and Distribution in the Microenvironment Based on Covalent Organic Framework Nanochannels.

A crack-free micrometer-sized compact structure of 1,3,5-tris(4-aminophenyl)benzene-terephthaldehyde-covalent organic frameworks (TAPB-PDA-COFs) was constructed in situ at the tip of a theta micropipette (TMP). The COF-covered theta micropipette (CTP) then created a stable liquid-gas interface inside COF nanochannels, which was utilized to electrochemically analyze the content and distribution of ammonia gas in the microenvironments. The TMP-based electrochemical ammonia sensor (TEAS) shows a high sensing response, with current increasing linearly from 0 to 50,000 ppm ammonia, owing to the absorption of ammonia gas in the solvent meniscus that connects both barrels of the TEAS. The TEAS also exhibits a short response and recovery time of 5 ± 2 s and 6 ± 2 s, respectively. This response of the ammonia sensor is remarkably stable and repeatable, with a relative standard deviation of 6% for 500 ppm ammonia gas dispensing with humidity control. Due to its fast, reproducible, and stable response to ammonia gas, the TEAS was also utilized as a scanning electrochemical microscopy (SECM) probe for imaging the distribution of ammonia gas in a microspace. This study unlocks new possibilities for using a TMP in designing microscale probes for gas sensing and imaging.

Synergistic Effect of Electrostatic Interaction and Ionic Dehydration on Asymmetric Ion Transport in Nanochannel/Ion Channel Composite Membrane.

Ion transport in nanochannels of a size comparable to that of hydrated ions exhibits unique properties due to the synergistic effect of various forces. Here, we design a nanochannel/ion channel composite (NIC) membrane that shows a high ion current rectification (ICR) ratio in different electrolytes. Experimental and theoretical results demonstrate that the synergistic effect of electrostatic interaction and ionic dehydration plays an important role in regulating the ICR behavior of the NIC membrane. We find that electrostatic attraction between ions and the channel surface in the ultraconfined space increases the probability of ionic dehydarion, resulting in different dehydration energy costs for different ions. This further alters the driving force for ion transport and thus regulates ICR of the NIC membrane. This work provides fundamental knowledge of ion transport in ion channels, which aids in the understanding of the function of biological systems and the design of high-performance nanochannel devices.

Bisphenol A biodegradation by Sphingonomas sp. YK5 is regulated by acyl-homoserine lactone signaling molecules.

Microbial degradation is an effective approach for the removal of Bisphenol A (BPA). During the biodegradation process, quorum sensing (QS) is a phenomenon that enables bacteria to coordinate collective behaviors based on cell density-dependent chemical signals. However, whether the degradation of BPA can be facilitated by this QS system (such as acyl-homoserine lactone, AHL) is unclear. To answer this question, the bifunctional Sphingonomas sp. strain YK5 that had BPA-degrading and AHL-producing properties was used. Biochemical analysis revealed that this bacterial strain mainly produced C8-HSL signals. Gene knockout experiments indicated that the AHL-system (LuxI1/LuxI2) was required for efficient BPA degradation. RT-PCR analyses revealed that the AHL system positively regulated the relative expression of genes (bisdA, CYP450, hapA, ligAB, and proB) involved in BPA degradation. Given that AHL signaling may be a common trait among BPA-degrading microorganisms and AHL system can regulate the degradation activity, manipulation of this system may be a valuable strategy to control BPA biodegradation.

Recognition of plastic nanoparticles using a single gold nanopore fabricated at the tip of a glass nanopipette.

A single gold nanopore with high surface enhanced Raman spectroscopy (SERS) activity is fabricated on the tip of a glass nanopipette. Polystyrene (PS) nanospheres can be recognized from the SERS spectrum while passing through the single nanopore.

A Novel Peptide from Abalone (Haliotis discus hannai) to Suppress Metastasis and Vasculogenic Mimicry of Tumor Cells and Enhance Anti-Tumor Effect In Vitro.

Vasculogenic mimicry (VM) formed by tumor cells plays a vital role in the progress of tumor, because it provides nutrition for tumor cells and takes away the metabolites. Therefore, the inhibition of VM is crucial to the clinical treatment of tumors. In this study, we investigated the anti-tumor effect of a novel peptide, KVEPQDPSEW (AATP), isolated from abalone (Haliotis discus hannai) on HT1080 cells by migration, invasion analysis and the mode of action. The results showed that AATP effectively inhibited MMPs by blocking MAPKs and NF-κB pathways, leading to the downregulation of metastasis of tumor cells. Moreover, AATP significantly inhibited VM and pro-angiogenic factors, including VEGF and MMPs by suppression of AKT/mTOR signaling. In addition, molecular docking was used to study the interaction of AATP and HIF-1α, and the results showed that AATP was combined with an active site of HIF-1α by a hydrogen bond. The effect of AATP on anti-metastatic and anti-vascular in HT1080 cells revealed that AATP may be a potential lead compound for treatment of tumors in the future.

Preparation and application of magnetic nitrogen-doped rGO for persulfate activation.

A heterogeneous catalyst (M-N-rGO) composed of stability enhanced magnetic iron oxide nanoparticles and nitrogen-doped reduced graphene oxide was synthesized and characterized by SEM, XRD, BET, and XPS. It showed excellent catalytic degradation properties in advanced oxidation technology. In the presence of 200 mg/L catalyst and 135 mg/L persulfate at pH 5, 95% of 10-20 mg/L methylene blue could be degraded in 90 min with the TOC removal efficiency of 50%. The rate constant based on pseudo-first-order kinetics ranged from 0.0227 to 0.0488/min in the temperature range of 15 to 32 °C, and the activation energy was 32.5 kJ/mol. Under the optimal operation conditions, 20 mg/L of 2,4-dichlorophneol (2,4-DCP) could be removed almost completely. EPR analysis showed that sulfate and hydroxyl radicals were responsible for degradation of pollutants, and radical quenching experiments indicated that nonradical pathway also played a role in pollutant removal. And a mechanism for M-N-rGO and persulfate system was elucidated. This catalyst was easy for preparation, low-cost, highly effective, convenient for separation, and could be used effectively for four times through 0.1 mol/L H2SO4 regeneration. It provided a choice for wastewater treatment in practice.

Propagation of concentration polarization affecting ions transport in branching nanochannel array.

A new ionic current rectification device responsive to a broad range of pH stimuli has been fabricated using porous anodic alumina membrane with tailor-made branching nanochannel array. The asymmetric geometry is achieved by changing oxidation voltage using a simple two-step anodization process. Due to the protonation/deprotonation of the intrinsic hydroxyl groups upon solution pH variation, the nanochannels array-based device is able to regulate ionic current rectification properties. The ion rectification ratio of the device is mainly determined by the branching size and surface charges, which is also confirmed by theoretical simulations. In addition, theoretical simulations show that the slight difference in ion rectification ratio for the nanochannel devices with different branching numbers is due to the propagation of concentration polarization. Three dimensional simulations clearly show the nonuniform concentration profiles in stem nanochannel near the junction interface due to the presence of branching nanochannels. The present ionic device is promising for biosensing, molecular transport and separation, and drug delivery in confined environments.

[Endoplasmic reticulum stress promotes the apoptosis of testicular germ cells in hyperlipidemic rats].

OBJECTIVE: To investigate the role of endoplasmic reticulum stress in the apoptosis of testicular germ cells in hyperlipidemic rats. METHODS: We randomly assigned 42 four-week-old male Wistar rats into a normal control group (n = 12) and a high-fat group (n = 30) to be fed on a normal diet and a high-fat diet, respectively, for 10 weeks. Then we measured the concentrations of triglyceride (TG) and total cholesterol (TC) in the serum using an automatic biochemistry analyzer, detected the apoptosis of testicular germ cells by TUNEL staining, and determined the protein and mRNA expressions of GRP78 and. caspase-12 in the testis tissue by immunohistochemistry and RT-PCR, respectively. RESULTS: The concentrations of TG and TC were significantly increased in the animals of the high-fat group ([3.00 ± 0.92] and [3.04 ± 0.39] mmol/L) as compared with the control rats ([1.43 ± 0.41] and [1.55 ± 0.23] mmol/L) (P < 0.01), and so was the apoptosis index of the testicular germ cells ([37.17 ± 2.74]% vs [5.16 ± 0.81]%, P < 0.01). The high-fat group, in comparison with the control, also showed remarkably upregulated protein and mRNA expressions of GRP78 (0.32 ± 0.03 and 0.86 ± 0.05 vs 0.19 ± 0.01 and 0.37 ± 0.03, P < 0.01) and caspase-12 (0.34 ± 0.02 and 0.87 ± 0.01 vs 0.12 ± 0.01 and 0.34 ± 0.03, P < 0.01) in the testis tissue. CONCLUSION: The apoptosis of testicular germ cells is increased in hyperlipidemic rats, which may be attributed to endoplasmic reticulum stress.

Signal-amplified platform for electrochemical immunosensor based on TiO2 nanotube arrays using a HRP tagged antibody-Au nanoparticles as probe.

In this study, a novel signal-amplified electrochemical immunosensor was proposed by using TiO(2) nanotube (TiNT) arrays as the platform. Due to the distinct tubular features-large surface area, high pore volume and good electrochemical conductivity, the TiNT based electrodes exhibited excellent signal-amplified effects. gold nanoparticle (AuNP) was further utilized to bind horseradish peroxidase (HRP) tagged antibodies as recognition elements. Compared to the immunosensor based on either flat electrode, the immunosensors using TiNT layer as electrode showed higher amplified electrochemical signals from the catalytic reaction of HRP relative to hydrogen peroxide (H(2)O(2)). Under optimal conditions, the proposed immunosensor exhibited a good electrochemical behavior to antigen in a concentration range from 0.1 ng mL(-1) to 10(5) ng mL(-1) with a detection limit of 0.01 ng mL(-1). The results showed that the TiNT-based electrochemical immunosensing platform could provide a great potential in clinical application for detection of low-abundant proteins.

Biotemplated synthesis of Au nanoparticles-TiO2 nanotube junctions for enhanced direct electrochemistry of heme proteins.

Au nanoparticles (AuNPs) are assembled on TiO(2) nanotube (TiNT) arrays by combining a biotemplating method with the unique photocatalytic properties of TiO(2). The formed AuNPs-TiNT junctions show highly improved electrochemical conductivity and act as electrode materials to achieve the enhanced direct electrochemistry of heme proteins.

A nanochannel array based device for determination of the isoelectric point of confined proteins.

A nanochannel array based nanodevice can mimic the biological environments and thus unveil the natural properties, conformation and recognition information of biomolecules such as proteins and DNA in confined spaces. Here we report that porous anodic alumina (PAA) of a highly parallel nanochannel array covalently modified with proteins significantly modulates the transport of a negatively charged probe of ferricyanide due to the electrostatic interactions between the probes and modified nanochannel inner surface. Results show that such electrostatic interaction exists in a wide range of ionic strength from 1 mM to 100 mM in 20 nm nanochannels modified with proteins (hemoglobin, bovine serum albumin, and goat anti-rabbit IgG secondary antibody). In addition, the maximal steady-state flux of the charged probe through the modified nanochannel array is directly related to the ionic strength which determines the electric double layer thickness and solution pH which modulates the nanochannel surface charge. Thus, the modulated mass transport of the probe by solution pH can be used to study the charge properties of the immobilized proteins in nanochannel confined conditions, leading us to obtain the isoelectric point (pI) of the proteins confined in nanochannels. The determined pI values of two known proteins of hemoglobin and bovine serum albumin are close to the ones of the same proteins covalently modified on a 3-mercaptopropionic acid self-assembled monolayer/gold electrode. In addition, the pI of an unknown protein of goat anti-rabbit IgG secondary antibody confined in nanochannels was determined to be 6.3. Finally, the confinement effect of nanochannels on the charge properties of immobilized proteins has been discussed.

[Diet-induced obesity increases the apoptosis of testicular spermatogenic cells in pubertal male rats].

OBJECTIVE: To investigate the effect of diet-induced obesity on the apoptosis of testicular spermatogenic cells in pubertal male rats. METHODS: Forty healthy male rats were equally and randomly divided into a control and a high-fat group, the former fed on normal diet, while the latter high-fat and high-calorie diet. The testes of the rats were harvested at the end of 10 weeks for detection of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) in the peripheral blood with the automatic biochemical analyzer. Pathological changes of the testis were observed under the light microscope, the apoptosis of the testicular cells detected by TUNEL, the expressions of Bcl-2 and Bax proteins determined by immunohistochemistry, and those of Bcl-2 mRNA and Bax mRNA measured by RT-PCR. RESULTS: The levels of TC, TG, LDL-C and HDL-C were significantly higher in the high-fat group (5.17 +/- 0.17, 1.18 +/- 0.09, 1.76 +/- 0.11 and 5.08 +/- 0.18) than in the control (1.38 +/- 0.12, 0.39 +/- 0.05, 0.97 +/- 0.07 and 0.75 +/- 0.06) (P < 0.05), so was the apoptotic index of spermatogenic cells (37.17 +/- 2.74 versus 5.16 +/- 0.81, P < 0.01), and the apoptotic spermatogenic cells were mainly spermatogonia and spermatocytes. The expressions of Bax protein and Bax mRNA were markedly higher in the high-fat group (153.26 +/- 8.74 and 1.08 +/- 0.12) than in the control (101.81 +/- 6.14 and 0.37 +/- 0.04) (P < 0.01), while those of Bcl-2 protein and Bcl-2 mRNA remarkably lower in the former (139.26 +/- 7.21 and 0.46 +/- 0.05) than in the latter (159.37 +/- 8.96 and 1.05 +/- 0.11) (P < 0.01). CONCLUSION: Diet-induced obesity can increase the apoptosis of spermatogenic cells in the rat testis, which may be associated with the reduced expression of Bcl-2 and elevated expression of Bax.