Simultaneous thulium laser resection of the prostate and transperineal prostate biopsy in clinically diagnosed metastatic prostate cancer with bladder outlet obstruction.

Metastatic prostate cancer (mPCa) patients complicated with bladder outlet obstruction (BOO) are often referred to a urologist. Androgen deprivation therapy (ADT) combined with indwelling catheter usually be the initial management. To retrospectively analysis the safety and efficacy of simultaneous thulium laser resection of the prostate (TmLRP) and transperineal prostate biopsy in metastatic prostate cancer with bladder outlet obstruction. From January 2016 to December 2021, 67 clinically diagnosed mPCa with BOO patients were included in this study. All patients were preoperatively assessed with international prostate symptom score (IPSS), QoL, serum prostate-specific antigen (PSA), prostate volume evaluation by transrectal ultrasound, postvoid residual urine volume (PVR), and maximum flow rate (Qmax). Preoperative and perioperative parameters at 1-, 3-, and 6-month follow-up were also evaluated. All complications were recorded. Simultaneous TmLRP and transperineal prostate biopsy had obvious advantages for clinically diagnosed mPCa patients with BOO, including short overall operation time (52 ± 23.3 min), little hemoglobin decrease (0.6 ± 0.7 g/l), and short hospital stay (average 3.8 days). In addition, simultaneous TmLRP and transperineal prostate biopsy also brought them significant improvement on IPSS, QoL score, Qmax, and PVR volume (P < 0.001) at 1-, 3-, and 6-month follow-up after operation compared to preoperative parameters. Complications were in a low incidence. Simultaneous TmLRP and transperineal prostate biopsy is a bloodless operation with immediate effect and little perioperative complication. Importantly, it is a promising technology in the diagnosis and treatment of clinically diagnosed mPCa patients with BOO.

ROS-NLRP3 signaling pathway induces sterile inflammation after thulium laser resection of the prostate.

The sterile inflammation (SI) of the urinary tract is a common problem requiring serious consideration after prostatectomy. This study mainly focuses on the role of the reactive oxygen species-NLR family, pyrin domain-containing 3 (ROS-NLRP3) signaling pathway in SI after thulium laser resection of the prostate (TmLRP). Urinary cytokines were determined in patients who received TmLRP, and heat shock protein 70 (HSP70) was detected in the resected tissues. The involvement of ROS signaling in HSP70-induced inflammation was explored in THP-1 cells with or without N-acetyl- l-cysteine (NAC) pretreatment. The function of NLRP3 and Caspase-1 was determined by Western blot analysis, enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction. These phenomena and mechanisms were verified by the beagle models that received TmLRP. Clinical urine samples after TmLRP showed high expression of inflammatory factors and peaked 3-5 days after surgery. The high expression of HSP70 in the resected tissues was observed. After HSP70 stimulation, the expression of ROS, NLRP3, Caspase-1, and interleukin-18 (IL-18) increased significantly and could be reduced by ROS inhibitor NAC. The expression of IL-1ß and IL-18 could be inhibited by NLRP3 or Caspase-1 inhibitors. In beagle models that received TmLRP, HSP70, NLRP3, Caspase-1, IL-1ß, and IL-18 were highly expressed in the wound tissue or urine, and could also be reduced by NAC pretreatment. Activation of the ROS-NLRP3 signaling pathway induces SI in the wound after prostatectomy. Inhibition of this pathway may be effective for clinical prevention and treatment of SI and related complications after prostatectomy.

Pharmacological Characterization of the Novel and Selective α7 Nicotinic Acetylcholine Receptor-Positive Allosteric Modulator BNC375.

Treatments for cognitive deficits associated with central nervous system (CNS) disorders such as Alzheimer disease and schizophrenia remain significant unmet medical needs that incur substantial pressure on the health care system. The α7 nicotinic acetylcholine receptor (nAChR) has garnered substantial attention as a target for cognitive deficits based on receptor localization, robust preclinical effects, genetics implicating its involvement in cognitive disorders, and encouraging, albeit mixed, clinical data with α7 nAChR orthosteric agonists. Importantly, previous orthosteric agonists at this receptor suffered from off-target activity, receptor desensitization, and an inverted U-shaped dose-effect curve in preclinical assays that limit their clinical utility. To overcome the challenges with orthosteric agonists, we have identified a novel selective α7 positive allosteric modulator (PAM), BNC375. This compound is selective over related receptors and potentiates acetylcholine-evoked α7 currents with only marginal effect on the receptor desensitization kinetics. In addition, BNC375 enhances long-term potentiation of electrically evoked synaptic responses in rat hippocampal slices and in vivo. Systemic administration of BNC375 reverses scopolamine-induced cognitive deficits in rat novel object recognition and rhesus monkey object retrieval detour (ORD) task over a wide range of exposures, showing no evidence of an inverted U-shaped dose-effect curve. The compound also improves performance in the ORD task in aged African green monkeys. Moreover, ex vivo 13C-NMR analysis indicates that BNC375 treatment can enhance neurotransmitter release in rat medial prefrontal cortex. These findings suggest that α7 nAChR PAMs have multiple advantages over orthosteric α7 nAChR agonists for the treatment of cognitive dysfunction associated with CNS diseases. SIGNIFICANCE STATEMENT: BNC375 is a novel and selective α7 nicotinic acetylcholine receptor (nAChR) positive allosteric modulator (PAM) that potentiates acetylcholine-evoked α7 currents in in vitro assays with little to no effect on the desensitization kinetics. In vivo, BNC375 demonstrated robust procognitive effects in multiple preclinical models across a wide exposure range. These results suggest that α7 nAChR PAMs have therapeutic potential in central nervous system diseases with cognitive impairments.

MK-8719, a Novel and Selective O-GlcNAcase Inhibitor That Reduces the Formation of Pathological Tau and Ameliorates Neurodegeneration in a Mouse Model of Tauopathy.

Deposition of hyperphosphorylated and aggregated tau protein in the central nervous system is characteristic of Alzheimer disease and other tauopathies. Tau is subject to O-linked N-acetylglucosamine (O-GlcNAc) modification, and O-GlcNAcylation of tau has been shown to influence tau phosphorylation and aggregation. Inhibition of O-GlcNAcase (OGA), the enzyme that removes O-GlcNAc moieties, is a novel strategy to attenuate the formation of pathologic tau. Here we described the in vitro and in vivo pharmacological properties of a novel and selective OGA inhibitor, MK-8719. In vitro, this compound is a potent inhibitor of the human OGA enzyme with comparable activity against the corresponding enzymes from mouse, rat, and dog. In vivo, oral administration of MK-8719 elevates brain and peripheral blood mononuclear cell O-GlcNAc levels in a dose-dependent manner. In addition, positron emission tomography imaging studies demonstrate robust target engagement of MK-8719 in the brains of rats and rTg4510 mice. In the rTg4510 mouse model of human tauopathy, MK-8719 significantly increases brain O-GlcNAc levels and reduces pathologic tau. The reduction in tau pathology in rTg4510 mice is accompanied by attenuation of brain atrophy, including reduction of forebrain volume loss as revealed by volumetric magnetic resonance imaging analysis. These findings suggest that OGA inhibition may reduce tau pathology in tauopathies. However, since hundreds of O-GlcNAcylated proteins may be influenced by OGA inhibition, it will be critical to understand the physiologic and toxicological consequences of chronic O-GlcNAc elevation in vivo. SIGNIFICANCE STATEMENT: MK-8719 is a novel, selective, and potent O-linked N-acetylglucosamine (O-GlcNAc)-ase (OGA) inhibitor that inhibits OGA enzyme activity across multiple species with comparable in vitro potency. In vivo, MK-8719 elevates brain O-GlcNAc levels, reduces pathological tau, and ameliorates brain atrophy in the rTg4510 mouse model of tauopathy. These findings indicate that OGA inhibition may be a promising therapeutic strategy for the treatment of Alzheimer disease and other tauopathies.

Immunogenic potential and protective efficacy of a sptP deletion mutant of Salmonella Enteritidis as a live vaccine for chickens against a lethal challenge.

Salmonella Enteritidis (SE) is a highly adapted pathogen causing severe economic losses in the poultry industry worldwide. Chickens infected by SE are a major source of human food poisoning. Vaccination is an effective approach to control SE infections. This study evaluated the immunogenicity and protective efficacy of a SE sptP deletion mutant (C50336ΔsptP) as a live attenuated vaccine (LAV) candidate in chickens. 14 day-old specific pathogen-free (SPF) chickens were intramuscularly immunized with various doses of C50336ΔsptP. Several groups of chickens were challenged with the virulent wild-type SE strain Z-11 via the same route at 14 days post vaccination. Compared to the control group, the groups vaccinated with 1 × 106, 1 × 107 and 1 × 108 colony-forming units (CFU) of C50336ΔsptP exhibited no clinical symptoms after immunization. Only slight pathological changes occurred in the organs of the 1 × 109 CFU vaccinated group. C50336ΔsptP bacteria were cleared from the organs of immunized chickens within 14 days after vaccination. Lymphocyte proliferation and serum cytokine analyses indicated that significant cellular immune responses were induced after the vaccination of C50336ΔsptP. Compared to the control group, specific IgG antibody levels increased significantly in vaccinated chickens, and the levels increased markedly after the challenge. The 1 × 107, 1 × 108, and 1 × 109 CFU vaccinated chickens groups showed no clinical symptoms or pathological changes, and no death after the lethal challenge. Whereas severe clinical signs of disease and pathological changes were observed in the control group chickens after the challenge. These results suggest that a single dose of C50336ΔsptP could be an effective LAV candidate to against SE infection in chickens.

Thulium laser enucleation versus thulium laser resection of the prostate for prevention of bladder neck contracture in a small prostate: a prospective randomized trial.

PURPOSE: To compare the safety and efficacy of thulium laser enucleation of the prostate (ThuLEP) versus thulium laser resection of the prostate (TmLRP) in small prostates (≤ 30 g) and to test the validity of ThuLEP for bladder neck contracture (BNC). METHODS: A total of 115 patients with benign prostatic hyperplasia (BPH) (prostate size ≤ 30 g) were randomly assigned to ThuLEP (n = 56) or TmLRP (n = 59). All patients were evaluated preoperatively and at 1, 3, 6, and 12 months after surgery. Baseline characteristics of the patients, perioperative data, postoperative outcomes and complications were assessed. RESULTS: Comparisons of the baseline and perioperative data demonstrated no significant differences between the ThuLEP and TmLRP groups. Significant improvement was noted in the International Prostate Symptom Score, quality of life, maximal urinary flow rate (Qmax) and post-void residual volume (PVR) in both groups at the 12-month follow-up, and assessment showed no differences in these parameters between the two groups. The TmLRP group showed a significantly higher rate (13.6%) of BNC than the ThuLEP group (1.8%; P = 0.045). There were no significant differences in other complications between the two groups (P > 0.05). CONCLUSIONS: ThuLEP and TmLRP are both safe and efficient procedures for the treatment of patients with small prostate volume, while ThuLEP can significantly reduce the risk of BNC in patients with a small prostate because the procedure enucleates adenomas without thermal damage to the bladder neck.

fMRI study of the role of glutamate NMDA receptor in the olfactory adaptation in rats: Insights into cellular and molecular mechanisms of olfactory adaptation.

Olfactory adaptation, characterized by attenuation of response to repeated odor stimulations or continuous odor exposure, is an intrinsic feature of olfactory processing. Adaptation can be induced by either "synaptic depression" due to depletion of neurotransmitters, or "enhanced inhibition" onto principle neurons by local inhibitory interneurons in olfactory structures. It is not clear which mechanism plays a major role in olfactory adaptation. More importantly, molecular sources of enhanced inhibition have not been identified. In this study, olfactory responses to either repeated 40-s stimulations with interstimulus intervals (ISI) of 140-s or 30-min, or a single prolonged 200-s stimulus were measured by fMRI in different naïve rats. Olfactory adaptations in the olfactory bulb (OB), anterior olfactory nucleus (AON), and piriform cortex (PC) were observed only with repeated 40-s odor stimulations, and no olfactory adaptations were detected during the prolonged 200-s stimulation. Interestingly, in responses to repeated 40-s odor stimulations in the PC, the first odor stimulation induced positive activations, and odor stimulations under adapted condition induced negative activations. The negative activations suggest that "sparse coding" and "global inhibition" are the characteristics of olfactory processing in PC, and the global inhibition manifests only under an adapted condition, not a naïve condition. Further, we found that these adaptations were NMDA receptor dependent; an NMDA receptor antagonist (MK801) blocked the adaptations. Based on the mechanism that glutamate NMDA receptor plays a role in the inhibition onto principle neurons by interneurons, our data suggest that the olfactory adaptations are caused by enhanced inhibition from interneurons. Combined with the necessity of the interruption of odor stimulation to observe the adaptations, the molecular source for the enhanced inhibition is most likely an increased glutamate release from presynaptic terminals due to glutamate over-replenishment during the interruption of odor stimulation. Furthermore, with blockage of the adaptations, the data reveal that orbital, medial & prefrontal, and cingulate cortices (OmPFC) are involved in the olfactory processing.

Association of endothelin-1 gene single-nucleotide polymorphisms and haplotypes with risk of hormone refractory prostate cancer.

Androgen deprivation is often the treatment of choice for patients with a new diagnosis of metastatic or locally advanced prostate cancer (CaP). However, most CaP patients showing a first response to androgen deprivation will progress to a hormone refractory phase of the disease (HRPC) with a much poorer prognosis. Accumulating evidence suggests that endothelin-1 (ET-1) plays an important role in CaP progression. Singlenucleotide polymorphisms (SNPs) of the ET-1 gene reportedly have been associated with cancer progression and chemoresistance. In the present study, we explored the association of SNPs and haplotypes of the ET-1 gene with the risk of HRPC. We genotyped three SNPs (rs1800541, rs2070699 and rs5370) in the ET-1 gene in a case-control study; 234 CaP patients who developed HRPC within six years after androgen deprivation therapy was used as HRPC cases, and 234 age- and primary therapy-matched CaP patients who had not developed HRPC within six years after androgen deprivation therapy were used as non-HRPC controls. Our results revealed that the G allele at rs1800541 and the G allele at rs2070699 were respectively associated with reduced and increased risk of HRPC at borderline statistical significance (p=0.047 and p=0.058, respectively). With adjustment for potential confounders including body mass index, initial Gleason score at diagnosis of CaP, and post-treatment nadir serum PSA level, we found that rs1800541-rs2070699 TG haplotype was significantly associated with increased risk of HRPC (p=0.033; adjusted OR, 2.10; 95% CI, 1.37-5.04). In conclusion, this study provides the first evidence that a 2-SNP haplotype of the ET-1 gene is associated with increased risk of HRPC, which adds new insights into early identification of CaP patients who are likely to develop HRPC in a later stage of the disease.

fMRI study of olfaction in the olfactory bulb and high olfactory structures of rats: Insight into their roles in habituation.

Cerebral blood volume (CBV) fMRI with ultrasmall superparamagnetic iron oxide particles (USPIO) as a contrast agent was used to investigate olfactory processing in rats. fMRI data were acquired in sixteen 0.75-mm coronal slices covering the olfactory bulb (OB) and higher olfactory regions (HOR), including the anterior olfactory nucleus and piriform cortex. For each animal, multiple consecutive fMRI measurements were made during a 3-h experiment session, with each measurement consisting of a baseline period, an odorant stimulation period, and a recovery period. Two different stimulation paradigms with a stimulation period of 40s or 80s, respectively, were used to study olfactory processing. Odorant-induced CBV increases were robustly observed in the OB and HOR of each individual animal. Olfactory adaptation, which is characterized by an attenuation of responses to continuous exposure or repeated stimulations, has different characteristics in the OB and HOR. For adaptation to repeated stimuli, while it was observed in both the OB and HOR, CBV responses in the HOR were attenuated more significantly than responses in the OB. In contrast, within each continuous 40-s or 80-s odor exposure, CBV responses in the OB were stable and did not show adaptation, but the CBV responses in the HOR were state dependent, with no adaptation during initial exposures, but significant adaptation during following exposures. These results support previous reports that HOR plays a more significant role than OB in olfactory habituation. The technical approach presented in this study should enable more extensive fMRI studies of olfactory processing in rats.

Long non-coding RNA lnc-MX1-1 is associated with poor clinical features and promotes cellular proliferation and invasiveness in prostate cancer.

Long non-coding RNAs (lncRNAs) are emerging as key molecules in human cancer genesis and progression, including prostate cancer. Large amount of lncRNAs have been found that differentially expressed between prostate cancer tissues and normal prostate tissues. Whether these lncRNAs could serve as a novel biomarker for prostate cancer diagnosis or prognosis, and their biological functions in prostate cancer need further investigation. In the present study, we identified that lncRNA lnc-MX1-1 is over-expressed in prostate cancer tissues compared with their adjacent normal prostate tissues by gene expression array profiling. The expression of lnc-MX1-1 in 60 prostate cancer cases was determined by real-time quantitative PCR and the correlations between lnc-MX1-1 expression and patients' clinical features were further analyzed. Next, we impaired lnc-MX1-1 expression using RNAi in LNCaP and 22Rv1 prostate cancer cells to explore the effects of lnc-MX1-1 on proliferation and invasiveness of the cells. Our results showed that there was a significant association between over-expression of lnc-MX1-1 and patients' clinical features such as PSA, Gleason score, metastasis, and recurrence free survival. Moreover, knockdown of lnc-MX1-1 reduced both proliferation and invasiveness of LNCaP and 22Rv1 cells. In conclusion, the results suggest that lnc-MX1-1 may serve as a potential biomarker and therapeutic target for prostate cancer.

Clinical evaluation and technical features of three-dimensional laparoscopic partial nephrectomy with selective segmental artery clamping.

PURPOSE: To investigate the feasibility and effectiveness of three-dimensional laparoscopic partial nephrectomy with selective segmental artery clamping (3D-LPNSSAC) comparing with the conventional two-dimensional laparoscopic partial nephrectomy (2D-LPN). METHODS: Between November 2012 and March 2014, 90 patients with cT1 renal tumor at Shanghai General Hospital were enrolled in our study, which were randomly divided into two groups: the 3D-LPNSSAC group (n = 45) and 2D-LPN group (n = 45). The perioperative variables, including operative time, dissecting time, suturing time, blood loss, warm ischemia time (WIT), preoperative and postoperative renal functions, were recorded and analyzed. In addition, the oncological outcomes and complications were also evaluated. RESULTS: All the LPNs were performed successfully without conversion to radical nephrectomy or open surgery, only three cases were converted to total renal artery clamping during 3D-LPNSSAC. There were no significant differences in operative time and dissecting time between the groups, while the suturing time was shorter during 3D-LPNSSAC (P < 0.01). The technique was associated with higher blood loss (P < 0.01). The technique of 3D-LPNSSAC significantly reduced WIT (P = 0.04), and better postoperative ipsilateral renal function could be obtained during 3D-LPNSSAC (P < 0.01). During a mean follow-up time of 16.8 months (range 5.5-22.5 months), the complication rate was 8.8 % (8/90) and no tumor reoccurrence was detected. CONCLUSIONS: 3D-LPNSSAC is a feasible and safe technique for treating selective renal tumors, presenting with the beneficial clinical outcomes of reduced suturing time, shorter WIT and better postoperative ipsilateral renal function.

Rapid manifestation of reactive astrogliosis in acute hippocampal brain slices.

A flurry of studies over the past decade has shown that astrocytes play a more active role in neural function than previously recognized. Hippocampal slices prepared from young rodent pups have served as a popular model for studying the pathways by which astrocytes participate in synaptic transmission. It is, however, not known how well astrocytes tolerate traumatic injury and hypoxia, which are unavoidable when preparing acute slices. We here showed that astrocytes exhibit striking changes in expression of several receptors and structural proteins, including re-expression of the developmental marker nestin within 90 min following preparation of live vibratome slices. Moreover, immunoelectron microscopy showed a 2.7-fold loss of astrocytic processes in acute hippocampal slices prepared from glial fibrillary acidic protein-green fluorescent protein reporter mice. A sharp decrease in the number of mitochondria was also noted in acute slices, concurrently with an increase in mitochondrial size. Glycogen content decreased 3-fold upon slice preparation and did not recover despite stable recordings of field excitatory postsynaptic current. Analysis of Ca(2+) signaling showed that astrocytic responses to purine receptor and mGluR5 agonists differed in slice versus in vivo. These observations suggest that the functional properties and the fine structure of astrocytes in slices may be reflective of early stages of reactive gliosis and should be confirmed in vivo when possible.

Electromagnetic Field Drives the Bioelectrocatalysis of γ-Fe2O3-Coated Shewanella putrefaciens CN32 to Boost Extracellular Electron Transfer.

The microbial hybrid system modified by magnetic nanomaterials can enhance the interfacial electron transfer and energy conversion under the stimulation of a magnetic field. However, the bioelectrocatalytic performance of a hybrid system still needs to be improved, and the mechanism of magnetic field-induced bioelectrocatalytic enhancements is still unclear. In this work, γ-Fe2O3 magnetic nanoparticles were coated on a Shewanella putrefaciens CN32 cell surface and followed by placing in an electromagnetic field. The results showed that the electromagnetic field can greatly boost the extracellular electron transfer, and the oxidation peak current of CN32@γ-Fe2O3 increased to 2.24 times under an electromagnetic field. The enhancement mechanism is mainly due to the fact that the surface modified microorganism provides an elevated contact area for the high microbial catalytic activity of the outer cell membrane's cytochrome, while the magnetic nanoparticles provide a networked interface between the cytoplasm and the outer membrane for boosting the fast multidimensional electron transport path in the magnetic field. This work sheds fresh scientific light on the rational design of magnetic-field-coupled electroactive microorganisms and the fundamentals of an optimal interfacial structure for a fast electron transfer process toward an efficient bioenergy conversion.

Implementation of π-π interaction in AuNPs@GDY to boost the bioelectrocatalysis in enzymatic biofuel cells.

The main challenges (sluggish electron transfer, low energy density) hinder the future application of enzymatic biofuel cells (EBFCs), which urgent to take effective measures to solve these issues. In this work, a composite of Au nanoparticles decorated graphdiyne (AuNPs@GDY) is fabricated and employed as the carrier of enzyme (G6PDH), and a mechanism based on π-π interaction of electron transfer is proposed to understand bioelectrocatalysis processes. The results show that the AuNPs@GDY composite exhibits the highest current density among the three materials (GDY, AuNPs, and AuNPs@GDY), which is 3.4 times higher than that of GDY and 2.5 times higher than that of AuNPs. Furthermore, the results reveal that the AuNPs could increase the loading of enzymes and provide more active site for reaction, while GDY provides highly π-conjugated structure and unique sp/sp2-hybridized linkages interface. This work provides new insights to explore a theoretical basis for the development of more efficient bioelectrocatalytic systems.

Increased infiltrated macrophages in benign prostatic hyperplasia (BPH): role of stromal androgen receptor in macrophage-induced prostate stromal cell proliferation.

Infiltrated macrophages may play important roles in the development and progression of benign prostatic hyperplasia (BPH), but the underlying mechanisms remain largely unknown. We found increased macrophages infiltration in human and mouse BPH tissues. By establishing a co-culture transwell system, we found increased migration of macrophages and proliferation of prostate stromal cells during co-culture. Importantly, stromal androgen receptor (AR) could enhance the migration of macrophages and macrophage-mediated stromal cell proliferation. We identified CCL3 as an AR downstream player, and found CCL3 levels were notably increased in human and mouse BPH prostates. Ablation of prostate stromal AR in a mouse BPH model significantly reduced CCL3 expression levels in prostates. Consistently, targeting AR via an AR degradation enhancer, ASC-J9®, or neutralization of CCL3 with an antibody, resulted in suppression of macrophage migration and prostate stromal cell growth. Our study provides mechanistic insights on the regulation of prostate stromal cells by macrophages via stromal AR/CCL3 signaling pathways, which could potentially allow the development of therapeutic approaches for battling BPH with persistent inflammation.

The toxic effect of opioid analgesics on human sperm motility in vitro.

Opioid analgesics are the most common therapeutic analgesic for acute pain. In this study, the toxicological and pharmacological features of a group of opioid analgesics were characterized by the motility of human sperm. Aliquots of sperm were incubated with various concentrations of opioid analgesics in vitro. Computer-assisted sperm analysis was used to assess sperm motility at 15 minutes, 2 hours, and 4 hours after drug addition to the medium. Butorphanol and dezocine showed marked reduction of motility after incubation with sperm for 15 minutes. Butorphanol was more effective than dezocine in immobilizing sperm. Other opioids studied, such as fentanyl, alfentanil, and sufentanil, showed only partial inhibitory activity. Based on the data reported herein, we have found that butorphanol and dezocine exert a sperm-immobilizing effect. However, fentanyl, alfentanil, and sufentanil exhibit only partial inhibition of sperm motility. Given the increasing use of opioids and their potential effect on sperm motility, these findings are greatly relevant to male reproductive health.

Electrospinning Mo-Doped Carbon Nanofibers as an Anode to Simultaneously Boost Bioelectrocatalysis and Extracellular Electron Transfer in Microbial Fuel Cells.

The sluggish electron transfer at the interface of microorganisms and an electrode is a bottleneck of increasing the output power density of microbial fuel cells (MFCs). Mo-doped carbon nanofibers (Mo-CNFs) prepared with electrostatic spinning and high-temperature carbonization are used as an anode in MFCs here. Results clearly indicate that Mo2C nanoparticles uniformly anchored on carbon nanowire, and Mo-doped anodes could accelerate the electron transfer rate. The Mo-CNF ΙΙ anode delivered a maximal power density of 1287.38 mW m-2, which was twice that of the unmodified CNFs anode. This fantastic improvement mechanism is attributed to the fact that Mo doped on a unique nanofiber surface could enhance microbial colonization, electrocatalytic activity, and large reaction surface areas, which not only enable direct electron transfer, but also promote flavin-like mediated indirect electron transfer. This work provides new insights into the application of electrospinning technology in MFCs and the preparation of anode materials on a large scale.

Doping molybdenum oxides with different non-metal atoms to promote bioelectrocatalysis in microbial fuel cells.

The sluggish extracellular electron transfer has been known as one of the bottlenecks to limit the power density of microbial fuel cells (MFCs). Herein, molybdenum oxides (MoOx) are doped with various types of non-metal atoms (N, P, and S) by electrostatic adsorption, followed by high-temperature carbonization. The as-prepared material is further used as MFC anode. Results indicate that all different elements-doped anodes can accelerate the electron transfer rate, and the great enhancement mechanism is attributed to synergistic effect of dopped non-metal atoms and the unique MoOx nanostructure, which offers high proximity and a large reaction surface area to promote microbe colonization. This not only enables efficient direct electron transfer but also enriches the flavin-like mediators for fast extracellular electron transfer. This work renders new insights into doping non-metal atoms onto metal oxides toward the enhancement of electrode kinetics at the anode of MFC.

Rapamycin and Low-dose IL-2 Mediate an Immunosuppressive Microenvironment to Inhibit Benign Prostatic Hyperplasia.

Benign prostatic hyperplasia (BPH) is a condition that becomes more common with age and manifests itself primarily as the expansion of the prostate and surrounding tissues. However, to date, the etiology of BPH remains unclear. In this respect, we performed single-cell RNA sequencing of prostate transition zone tissues from elderly individuals with different prostate volumes to reveal their distinct tissue microenvironment. Ultimately, we demonstrated that a reduced Treg/CD4+ T-cell ratio in the large-volume prostate and a relatively activated immune microenvironment were present, characterized partially by increased expression levels of granzymes, which may promote vascular growth and profibrotic processes and further exacerbate BPH progression. Consistently, we observed that the prostate gland of patients taking immunosuppressive drugs usually remained at a smaller volume. Furthermore, in mouse models, we confirmed that both suppression of the immune system with rapamycin and induction of Treg proliferation with low doses of IL-2 therapy indeed prevented the progression of BPH. Taken together, our findings suggest that an activated immune microenvironment is necessary for prostate volume growth and that Tregs can reverse this immune activation state, thereby inhibiting the progression of BPH.

Targeting androgen receptor leads to suppression of prostate cancer via induction of autophagy.

PURPOSE: Androgen receptor has a critical role in prostate cancer development and progression. Cell death via autophagy may also contribute to prostate cancer progression. We determined the role and regulatory effects of androgen receptor on the autophagy process of prostate cancer cells. MATERIALS AND METHODS: Using a series of morphological approaches, such as transmission electron microscopy, monodansylcadaverine (Sigma®) and GFP-LC3 fluorescence microscopy assay, and Western blot we monitored the autophagic process in 3 pairs of prostate cancer cell lines to study the relationship to androgen receptor signals. RESULTS: Androgen receptor knockdown in androgen receptor positive cells, such as LNCaP or CWRrv1 human prostate cancer cells, led to increased autophagy. Adding functional androgen receptor to androgen receptor negative cells, such as PC3 human prostate cancer cells, resulted in decreased autophagy. This suggests that androgen receptor could have a negative role in regulating autophagy. Mechanism dissection indicated that androgen receptor might repress autophagy via modulation of p62 expression. A therapeutic approach of targeting androgen receptor to increase autophagy using the androgen receptor degradation enhancer ASC-J9® suppressed prostate cancer growth. CONCLUSIONS: Findings provide evidence that the androgen receptor might promote prostate cancer cell growth via autophagy down-regulation. Targeting the androgen receptor via ASC-J9 might lead to tumor suppression via the induction of autophagy. This may represent a new, potential therapeutic approach and mechanism for prostate cancer.