Tunable Magnetism in Atomically Thin Itinerant Antiferromagnet with Room-Temperature Ferromagnetic Order.

Addressing the need for modulated spin configurations is crucial, as they serve as the foundational building blocks for next-generation spintronics, particularly in atomically thin structures and at room temperature. In this work, we realize intrinsic ferromagnetism in monolayer flakes and tunable ferro-/antiferromagnetism in (Fe0.56Co0.44)5GeTe2 antiferromagnets. Remarkably, the ferromagnetic ordering (≥1 L) and antiferromagnetic ordering (≥4 L) remain discernible up to room temperature. The TC (∼310 K) of the monolayer flakes sets a record high for known exfoliated monolayer van der Waals magnets. Within the framework of A-type antiferromagnetism, a notable odd-even layer-number effect at elevated temperatures (T = 150 K) is observed. Of particular interest is the strong ferromagnetic order in even-layer flakes at low temperatures. The intricate interplay among magnetic field strength, layer number, and temperature gives rise to a diverse array of phenomena, holding promise not only for new physics but also for practical applications.

Sagittal balance parameters measurement on cervical spine MR images based on superpixel segmentation.

Introduction: Magnetic Resonance Imaging (MRI) is essential in diagnosing cervical spondylosis, providing detailed visualization of osseous and soft tissue structures in the cervical spine. However, manual measurements hinder the assessment of cervical spine sagittal balance, leading to time-consuming and error-prone processes. This study presents the Pyramid DBSCAN Simple Linear Iterative Cluster (PDB-SLIC), an automated segmentation algorithm for vertebral bodies in T2-weighted MR images, aiming to streamline sagittal balance assessment for spinal surgeons. Method: PDB-SLIC combines the SLIC superpixel segmentation algorithm with DBSCAN clustering and underwent rigorous testing using an extensive dataset of T2-weighted mid-sagittal MR images from 4,258 patients across ten hospitals in China. The efficacy of PDB-SLIC was compared against other algorithms and networks in terms of superpixel segmentation quality and vertebral body segmentation accuracy. Validation included a comparative analysis of manual and automated measurements of cervical sagittal parameters and scrutiny of PDB-SLIC's measurement stability across diverse hospital settings and MR scanning machines. Result: PDB-SLIC outperforms other algorithms in vertebral body segmentation quality, with high accuracy, recall, and Jaccard index. Minimal error deviation was observed compared to manual measurements, with correlation coefficients exceeding 95%. PDB-SLIC demonstrated commendable performance in processing cervical spine T2-weighted MR images from various hospital settings, MRI machines, and patient demographics. Discussion: The PDB-SLIC algorithm emerges as an accurate, objective, and efficient tool for evaluating cervical spine sagittal balance, providing valuable assistance to spinal surgeons in preoperative assessment, surgical strategy formulation, and prognostic inference. Additionally, it facilitates comprehensive measurement of sagittal balance parameters across diverse patient cohorts, contributing to the establishment of normative standards for cervical spine MR imaging.

Expression of HER2 in high-grade urothelial carcinoma based on Chinese expert consensus and the clinical effects of disitamab vedotin-tislelizumab combination therapy in the treatment of advanced patients.

Background: A vast number of researchers have discovered high levels of human epidermal growth factor receptor-2 (HER2) expression in urothelial carcinoma (UC), but they do not use a uniform scoring system. Based on the 2021 edition of clinical pathological expert consensus on HER-2 testing in UC in China, we investigated the expression level and clinical significance of HER2 in high-grade UC. Furthermore, we looked at the prognosis of patients with locally advanced/metastatic UC after combining HER2 targeting antibody-drug conjugates (ADC) medication disitamab vedotin (DV) with programmed cell death protein 1 (PD-1) inhibitor tislelizumab. Patients and methods: From 2019 to 2022, we collected paraffin specimens of UC from the Department of Urology at the Provincial Hospital Affiliated to Shandong First Medical University. HER2 expression-related factors were investigated. Patients with advanced UC who have failed systemic chemotherapy at least once and had received immune checkpoint inhibitor (ICI) medication during second-line treatment were selected and treated with DV in combination with tislelizumab. We assessed the therapy's efficacy and safety. Results: 185 patients with high-grade UC were included in this investigation. 127 patients (68.7%) were HER2 positive (IHC 2+/3+) according to the 2021 Clinical pathological expert consensus on HER2 testing in UC in China. The clinical stage of UC differed statistically significantly between the HER2-and HER2+ groups (p = 0.019). Sixteen advanced UC patients were treated with DV and tislelizumab for a median of 14 months. The disease control rate was 87.5%, while the objective response rate (ORR) was 62.5%. The ORR of HER2+ individuals was higher than that of HER2-individuals (70.0% vs. 50.0%). The median progression-free survival or overall survival was not reached. In this study, the incidence of treatment-related adverse events was 68.8% (11/16), with all of them being grade 1 or 2 adverse reactions. Conclusion: HER2 protein expressed at a high percentage in UC, and 68.7% patients expressed HER2 positive (IHC 2+/3+). HER2+ expression is positively correlated with higher clinical stage of UC. HER2 targeted ADC drug disitamab vedotin combining with PD-1 inhibitor tislelizumab has shown efficacy, safety and controllable adverse reactions in the treatment of advanced UC.

Layer-Number-Dependent Magnetism in the Co-Doped van der Waals Ferromagnet Fe3GaTe2.

Recently, van der Waals (vdW) antiferromagnets have been proposed to be crucial for spintronics due to their favorable properties compared to ferromagnets, including robustness against magnetic perturbation and high frequencies of spin dynamics. High-performance and energy-efficient spin functionalities often depend on the current-driven manipulation and detection of spin states, highlighting the significance of two-dimensional metallic antiferromagnets, which have not been much explored due to the lack of suitable materials. Here, we report a new metallic vdW antiferromagnet obtained from the ferromagnet Fe3GaTe2 by cobalt (Co) doping. Through the layer-number-dependent Hall resistance and magnetoresistance measurements, an evident odd-even layer-number effect has been observed in its few-layered flakes, suggesting that it could host an A-type antiferromagnetic structure. This peculiar layer-number-dependent magnetism in Co-doped Fe3GaTe2 helps unravel the complex magnetic structures in such doped vdW magnets, and our finding will enrich material candidates and spin functionalities for spintronic applications.

Level pinning of anti-PT-symmetric circuits for efficient wireless power transfer.

Wireless power transfer (WPT) technology based on magnetic resonance (a basic physical phenomenon) can directly transfer energy from the source to the load without wires and other physical contacts, and has been successfully applied to implantable medical devices, electric vehicles, robotic arms and other fields. However, due to the frequency splitting of near-field coupling, the resonant WPT system has some unique limitations, such as poor transmission stability and low efficiency. Here, we propose anti-resonance with level pinning for high-performance WPT. By introducing the anti-resonance mode into the basic WPT platform, we uncover the competition between dissipative coupling and coherent coupling to achieve novel level pinning, and construct an effective anti-parity-time (anti-PT)-symmetric non-Hermitian system that is superior to previous PT-symmetric WPT schemes. On the one hand, the eigenvalue of the anti-PT-symmetric system at resonance frequency is always pure real in both strong and weak coupling regions, and can be used to overcome the transmission efficiency decrease caused by weak coupling, as brought about by, for example, a large size ratio of the transmitter to receiver, or a long transmission distance. On the other hand, due to the level pinning effect of the two kinds of coupling mechanisms, the working frequency of the system is guaranteed to be locked, so frequency tracking is not required when the position and size of the receiver change. Even if the system deviates from the matching condition, an efficient WPT can be realized, thereby demonstrating the robustness of the level pinning. The experimental results show that when the size ratio of the transmitter coil to the receiver coil is 4.29 (which is in the weak coupling region), the transfer efficiency of the anti-PT-symmetric system is nearly 4.3 (3.2) times higher than that of the PT-symmetric system when the matching conditions are satisfied (deviated). With the miniaturization and integration of devices in mind, a synthetic anti-PT-symmetric system is used to realize a robust WPT. Anti-PT-symmetric WPT technology based on the synthetic dimension not only provides a good research platform for the study of abundant non-Hermitian physics, but also provides a means of going beyond traditional near-field applications with resonance mechanisms, such as resonance imaging, wireless sensing and photonic routing.

Laparoscopy and ureteroscopy cooperative surgery for high burden stones in solitary kidney and ureter in one stage: A case report.

Treatment of kidney and ureter multiple calculi is a difficult procedure in urology. It is especially difficult to eliminate the high burden stones in a one-stage operation. When a patient has had only one kidney since he/she was born (a condition termed 'solitary kidney'), the conservation of the renal function is especially important. A series of combined surgery techniques have been developed, including endoscopic combined intrarenal surgery, extracorporeal shock wave lithotripsy sandwich therapy and laparoscopy-assisted percutaneous nephrolithotomy, but not laparoscopy or endoscopy cooperative surgery. The present study described the case of a patient with a solitary kidney and ureter who developed multiple calculi. This condition led to hydronephrosis and severe anuria for 3 days. Urinary ultrasound indicated hydronephrosis of the left kidney and several stones were detected. The maximum renal stone was sized ~2.7x0.8 cm. In addition, a maximally sized stone of 2.9x0.9 cm was found in the left upper ureter. The patient had only one kidney, the right kidney was absent. Laboratory examinations revealed severe renal dysfunction. A percutaneous nephrostomy was immediately performed on the left kidney. Laparoscopy, flexible ureteroscopy, rigid ureteroscopy and ureteroscope pneumatic lithotripsy were used to eliminate all the stones in one stage. The patient recovered well and was discharged on the eighth day post-surgery. The present case report highlighted that the conservation of kidney function is critical in the treatment of anuria lasting for 3 days in a patient with calculus. When the situation arises, laparoscopy combined with ureteroscopy cooperative surgery was shown to be a good choice for one-stage clearance of complex stones in patients with a solitary kidney and ureter.

Layer-Number-Dependent Magnetism and Anomalous Hall Effect in van der Waals Ferromagnet Fe5GeTe2.

Realization of ferromagnetism in the two-dimensional (2D) van der Waals (vdW) crystals opens up a vital route to understand the magnetic ordering in the 2D limit and to design novel spintronics. Here, we report enriched layer-number-dependent magnetotransport properties in the vdW ferromagnet Fe5GeTe2. By studying the magnetoresistance and anomalous Hall effect (AHE) in nanoflakes with thicknesses down to monolayer, we demonstrate that while the bulk crystals exhibit soft ferromagnetism with an in-plane magnetic anisotropy, hard ferromagnetism develops upon thinning, and a perpendicular easy-axis anisotropy is realized in bilayer flakes, which is accompanied by a pronounced enhancement of AHE because of extrinsic mechanisms. For the monolayer flakes, the hard ferromagnetism is replaced by spin-glass-like behavior, in accordance with the localization effect in the 2D limit. Our results highlight the thickness-based tunability of the magnetotransport properties in the atomically thin vdW magnets that promises engineering of high-performance spintronic devices.

Urine and Tissue Bacterial Loads Correlate With Voiding Behaviors in a Murine Urinary Tract Infection Model.

OBJECTIVES: To describe associations between voiding behavior and bacterial loads in a murine model of urinary tract infection (UTI). METHODS: Fourteen female C57BL/6J mice were transurethrally inoculated with 108colony-forming unit uropathogenic E. coli (UPEC) UTI89 in 50 µL two times, 24 hours apart. Voiding spot assays were used to measure voiding behavior. Voiding spot assays and urine cultures were performed at various time points between 1 and 28 days postinfection (dpi). Bladder and kidney bacterial loads were measured at 28 dpi. Correlations were calculated between voiding spot assay variables and bacterial loads at different dpi. In a separate experiment, 3 female mice were infected with UPEC in the same manner for histology changes at 28-dpi in chronic UTI. RESULTS: During the 28 days, among 14 mice, 8 developed chronic cystitis and 11 developed chronic pyelonephritis based on a priori definitions. All infected mice showed increased urinary frequency, polyuria, and decreased bladder capacity. Tissue fibrosis was also observed in the infected bladder. At 1 dpi and 28 dpi, the urinary bacterial loads were positively associated with frequency and polyuria. Bladder and kidney bacterial loads at 28 dpi were positively with frequency and polyuria. CONCLUSIONS: Urine and tissue bacterial loads were associated with changes of voiding behavior at both 1 and 28 dpi.

Actively controlled asymmetric edge states for directional wireless power transfer.

Wireless power transfer (WPT) has triggered immense research interest in a range of practical applications, including mobile phones, logistic robots, medical-implanted devices and electric vehicles. With the development of WPT devices, efficient long-range and robust WPT is highly desirable but also challenging. In addition, it is also very important to actively control the transmission direction of long-range WPT. Recently, the rise of topological photonics provides a powerful tool for near-field robust control of WPT. Considering the technical requirements of robustness, long-range and directionality, in this work we design and fabricate a one-dimensional quasiperiodic Harper chain and realize the robust directional WPT using asymmetric topological edge states. Specially, by further introducing a power source into the system, we selectively light up two Chinese characters, which are composed of LED lamps at both ends of the chain, to intuitively show the long-range directional WPT. Moreover, by adding variable capacitance diodes into the topological quasiperiodic chain, we present an experimental demonstration of the actively controlled directional WPT based on electrically controllable coil resonators. With the increase in voltage, we measure the transmission at two ends of the chain and observe the change of transmission direction. The realization of an actively tuned topological edge states in the topological quasiperiodic chain will open up a new avenue in the dynamical control of robust long-range WPT.

Profiles of Immune Infiltration in Bladder Cancer and its Clinical Significance: an Integrative Genomic Analysis.

Tumor-infiltrating immune cells are closely related to the prognosis of bladder cancer. Analysis of tumor infiltrating immune cells is usually based on immunohistochemical analysis. Since many immune cell marker proteins are not specific for different immune cells, which may induce misleading or incomplete. CIBERSORT is an algorithm to estimate specific cell types in a mixed cell population using gene expression data. In this study, the CIBERSORT algorithm was used to identify the immune cell infiltration signatures. The gene expression profiles, mutation data, and clinical data were collected from The Cancer Genome Atlas (TCGA) database. Unsupervised consensus clustering was used to acquire the immune cell infiltration subtypes of bladder cancer based on the fractions of 22 immune cell types. Four immune cell clusters with different immune infiltrate and mutation characteristics were identified. In addition, this stratification has a prognostic relevance, with cluster 2 having the best outcome, cluster 1 the worst. These clusters showed distinct mRNA expression patterns. The characteristic genes in subtype cluster 1 were mainly involved in cell division, those in subtype cluster 2 were mainly related in antigen processing and presentation, those in subtype cluster 3 were mainly involved in epidermal cell differentiation, and those in subtype cluster 4 were mainly related in the humoral immune response. These differences may affect the development of the bladder cancer, the sensitivity to treatment as well as the prognosis. Through further validation, this study may contribute to the development of personalized therapy and precision medical treatments.

Early Increased Urinary IL-2 and IL-10 Levels Were Associated With Development of Chronic UTI in a Murine Model.

OBJECTIVES: To analyze factors during early stage of urinary tract infection (UTI) that are associated with development of chronic UTI. METHODS: Mice were inoculated with Uropathogenic Escherichia coli (UPEC) 2 times 24 hours apart. At 1, 3, 7, 10, 14, 21 and 28 days post infection (dpi), urine bacterial loads and voiding behavior (voiding spot assay, VSA) were measured. At 1 and 28 dpi, 32 urine inflammatory cytokines/chemokines were measured using enzyme-linked immunosorbent assay (ELISA). Bladder and kidney cytokines/chemokines were measured on 28 dpi. Mice that had no more than 1 episode of urine bacterial load < 104 colony forming unit/ml during the entire 4 weeks were defined as susceptible to chronic UTI, otherwise, mice were considered resistant. RESULTS: At 28 dpi, 64.3% mice developed chronic UTI (susceptible group) and 35.7% mice did not (resistant group). Factors at 1 dpi that were predictive of chronic UTI included increased urine IL-2 (OR 11.9, 95%CI 1.1-130.8, P = .043) and increased urine IL-10 (OR 14.0, 95%CI 1.0-201.2, P = .052). At 28 dpi, there were several significant differences between the susceptible vs resistant groups including urine/tissue bacterial loads and certain urine/tissue cytokines/chemokines. CONCLUSIONS: Higher urine IL-2 and IL-10 at 1 dpi predicted chronic UTI infection in this model. There have been recent publications associating both of these cytokines to UTI susceptibility. Further explorations into IL-2 and IL-10 mediated pathways could shed light on the biology of recurrent and chronic UTI which are difficult to treat.

Identification of gene expression profiles and immune cell infiltration signatures between low and high tumor mutation burden groups in bladder cancer.

Bladder cancer is one of the most commonly diagnosed tumors and is results from the accumulation of somatic mutations in the DNA. Tumor mutation burden (TMB) has been associated with cancer immunotherapeutic response. In this study, we attempted to explore the correlation between TMB and cancer prognosis. Identify the different expressed genes and immune cell infiltration signatures between low and high TMB group. Mutation data, gene expression profiles and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. Patients were divided into high and low TMB groups, allowing differentially expressed genes (DEGs) to be identified. Functional enrichment and protein-protein interaction (PPI) network analysis were used to identify the functions of the DEGs. And immune cell infiltration signatures were evaluated by CIBERSORT algorithm. These results shown that high TMB was significantly associated with prognosis. We obtained a list of TMB related genes which may influence the infiltrations of immune cells. We also found a higher proportion of CD8 T cells, CD4 T cells and NK cells in the high TMB group. Our data suggest that higher TMB tends to promote the infiltrations of T cells and NK cells and patients with higher TMB may achieve a more favorable prognosis in bladder cancer.

Cigarette smoke induces the pyroptosis of urothelial cells through ROS/NLRP3/caspase-1 signaling pathway.

AIMS: Cell death and inflammation are involved in the development of bladder dysfunction. Pyroptosis is programmed cell death, causing cytotoxic effects and local inflammation. As one of the biggest health threats in the world, smoking is also closely related to urinary system diseases. The aims of this study were to investigate the role of NLRP3 inflammasome-mediated pyroptosis in the bladder after cigarette smoke exposure. METHODS: The expression of NLRP3 inflammasome and the activity of caspase-1 in bladder tissue was investigated after cigarette smoke exposure. In vitro, bladder urothelial cells were stimulated by cigarette smoke extract and then the activity of caspase-1 and the expression of NLRP3 inflammasome were measured. The role of oxidative stress was also assessed. RESULTS: The activity of caspase-1 in bladder tissue increased by 50% after cigarette smoke exposure. Cigarette smoke caused oxidative stress injury and the activation of NLRP3 inflammasome. In addition, reactive oxygen species (ROS) inhibitor N-acetyl-cysteine alleviated the pyroptosis of urothelial cells. CONCLUSIONS: Cigarette smoke-induced pyroptosis of bladder tissue by activating ROS/NLRP3/caspase-1 signaling pathway. Inhibition of bladder urothelial cell pyroptosis may be a new approach to alleviate bladder damage caused by smoking.

Ultra-thin NiS nanosheets as advanced electrode for high energy density supercapacitors.

Low energy density of supercapacitors is one of the major downsides for their practical applications. Here, a simple hydrothermal method was developed to synthesize NiS nanosheets on Ni foam. NiS nanosheets with a rough surface promise large electroactive surface area for energy storage, and show an ultra-high capacitance of 2587 F g-1 at a scan rate of 0.2 A g-1 (corresponding to the discharge time of 5563 s). The NiS nanosheets also present an outstanding cycling stability of 95.8% after 4000 cycles. As a positive electrode material for hybrid supercapacitors (HSC), NiS nanostructures provide a broad voltage window of 1.7 V. Our device also shows a high energy density of 38 W h kg-1 at a power density of 1.5 kW kg-1.

Cannabinoid receptor 2 activation decreases severity of cyclophosphamide-induced cystitis via regulating autophagy.

PURPOSE: Cannabinoids have been shown to exert analgesic and anti-inflammatory effects, and the effects of cannabinoids are mediated primarily by cannabinoid receptors 1 and 2 (CB1 and CB2). The objective of this study was to determine efficacy and mechanism of CB2 activation on cyclophosphamide (CYP)-induced cystitis in vivo. METHODS: Cystitis was induced by intraperitoneal (IP) injection of CYP in female C57BL/6J mice. Mice were pretreated with CB2 agonist JWH-133 (1 mg/kg, intraperitoneally), CB2 antagonist AM-630 (1 mg/kg, intraperitoneally) or autophagy inhibitor 3-methyladenine (3-MA) (50 mM, intraperitoneally) before IP injection of CYP. Peripheral nociception and spontaneous voiding were investigated in these mice. Bladders were collected, weighed, and processed for real-time polymerase chain reaction, immunoblotting analysis, histological and immunohistochemical analysis. RESULTS: Twenty-four hours after IP injection of CYP, the bladder of CYP-treated mice showed histological evidence of inflammation. The expression of CB2 in bladder was significantly increased in CYP-treated mice. Mechanical sensitivity was significantly increased in CYP-treated mice and CB2 agonist JWH-133 attenuated this effect (P < .05). The number of urine spots was significantly increased after CYP treatment and it was decreased in JWH-133 treated mice (P < .05). Activating CB2 with JWH-133 significantly alleviated bladder tissue inflammatory responses and oxidative stress induced by CYP. Activation of CB2 by JWH-133 increased the expression of LC3-II/LC3-I ratio, and decreased the expression of SQSTM1/p62 in the bladder of cystitis mice, whereas AM-630 induced inverse effects. Further study indicated that JWH-133 could promote autophagy and blocking autophagy by 3-MA dismissed the effort of CB2 in alleviating bladder tissue inflammatory responses and oxidative stress injury. Furthermore, treatment with 3-MA decreased the expression of p-AMPK and induced the phosphorylation of mTOR in the presence of JWH-133 stimulation in cystitis model. CONCLUSIONS: Activation of CB2 decreased severity of CYP-induced cystitis and ameliorated bladder inflammation. CB2 activation is protective in cystitis through the activation of autophagy and AMPK-mTOR pathway may be involved in the initiation of autophagy.

The Core-Shell Heterostructure CNT@Li2FeSiO4@C as a Highly Stable Cathode Material for Lithium-Ion Batteries.

The reasonable design of nanostructure is the key to solving the inherent defects and realizing a high performance of Li2FeSiO4 cathode materials. In this work, a novel heterostructure CNT@Li2FeSiO4@C has been designed and synthesized and used as a cathode material for lithium-ion battery. It is revealed that the product has a uniform core-shell structure, and the thickness of the Li2FeSiO4 layer and the outer carbon layer is about 19 nm and 2 nm, respectively. The rational design effectively accelerates the diffusion of lithium ions, improves the electric conductivity, and relieves the volume change during the charging/discharging process. With the advantages of its specific structure, CNT@Li2FeSiO4@C has successfully overcome the inherent shortcomings of Li2FeSiO4 and shown good reversible capacity and cycle properties.

Pyroptosis engagement and bladder urothelial cell-derived exosomes recruit mast cells and induce barrier dysfunction of bladder urothelium after uropathogenic E. coli infection.

The specific regulatory mechanism of bladder urothelial barrier dysfunction after infection with uropathogenic Escherichia coli (UPEC) is still unclear. The cross talk between bladder urothelial cells and mast cells may play an important role during UPEC infection. In this study, the pyroptosis of urothelial cells was investigated after UPEC infection both in vivo and in vitro. The levels of IL-1ß and IL-18 in exosomes derived from bladder urothelial cells after UPEC infection were detected. The role of these processes in the recruitment and activation of mast cells was measured. The mechanism of mast cell-induced disruption of bladder epithelial barrier function was also assessed. We found that UPEC infection induced pyroptosis of bladder urothelial cells and led to the release of IL-1ß and IL-18 in the form of exosomes, which promoted the migration of mast cells. Tryptase secreted by mast cells aggravated the damage to the barrier function of the bladder urothelium by acting on protease-activated receptor 2 (PAR2). Inhibition of pyroptosis or the tryptase-PAR2 axis reduced the disruption of bladder urothelial barrier function and decreased the bacterial burden. The present study supports a novel mechanism by which pyroptosis-dependent release of exosomes from bladder urothelial cells activates mast cells and regulates bladder urothelial barrier function during UPEC infection.

Role of GM-CSF in a mouse model of experimental autoimmune prostatitis.

The etiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is still unknown. Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to play an important role in the development of autoimmune and inflammatory diseases. Here, we investigated the expression and function of GM-CSF in patients with CP/CPPS and in a mouse model of experimental autoimmune prostatitis (EAP). GM-CSF mRNA levels were detected in expressed prostatic secretions samples from patients with CP/CPPS and in prostate tissue from a mouse model of EAP. The expression of GM-CSF receptor in mouse prostate and dorsal root ganglia were determined using PCR and immunohistochemistry. Behavioral testing and inflammation scoring were performed to evaluate the role of GM-CSF in disease development and symptom severity of EAP using GM-CSF knockout mice. mRNA levels of putative nociceptive and inflammatory markers were measured in the prostate after the induction of EAP. Elevated GM-CSF mRNA levels were observed in expressed prostatic secretions samples from patients with CP/CPPS compared with healthy volunteers. GM-CSF mRNA was also significantly increased in prostate tissue of the EAP mice model. The expression of GM-CSF receptors was confirmed in mouse prostate and dorsal root ganglia. GM-CSF knockout mice showed fewer Infiltrating leukocytes and pain symptoms after the induction of EAP. Deletion of GM-CSF significantly diminished EAP-induced increases of chemokine (C-C motif) ligand 2, chemokine (C-C motif) ligand 3, and nerve growth factor mRNA expression. The results indicated that GM-CSF plays a functional role in the pathogenesis of EAP. GM-CSF may function as a signaling mediator for both inflammation and pain transduction in CP/CPPS.

A non-enzymatic method for dissection of mouse bladder urothelial tissue.

Urothelial cells contribute to bladder functions, including urine storage, urine emptying, and innate immune response. Functional studies of urothelial cells usually use either freshly isolated cells or cultured cells. Most methods of isolating urothelial cells require enzymes; however, these techniques remove proteins that connect the cells and disrupt the orientation of the cells within the multilayered urothelium. In addition, PCR or immunoblot results obtained from homogenates of bladder mucosa or whole bladder do not represent pure urothelial cells. We describe a dissection process that does not require enzymes and is able to obtain pure urothelial tissues from mice and humans. This method can isolate single urothelial cells for electrophysiology in situ and can also isolate pure urothelial tissue for PCR, microarray, and immunoblot procedures. The time required to obtain urothelial tissue from one mouse bladder is 15-20 min. This method is simple and time efficient as compared with alternative methods and therefore facilitates our understanding of urothelial biology.

CCL17-CCR4 axis promotes metastasis via ERK/MMP13 pathway in bladder cancer.

As an important chemokine receptor, the role of CCR4 in the progression of bladder cancer (BC) remains unknown. In this study, we have shown that CCR4 expression was upregulated in bladder carcinoma tissues compared with adjacent nontumor tissues. Kaplan-Meier survival analysis revealed that CCR4 expression was an independent prognostic risk factor in BC patients, and the addition of CCL17 induced CCR4 production and promoted migration and invasion of BC cells. In addition, CCR4 knockdown significantly attenuated the migratory and invasive capabilities of BC cells. Mechanistically, CCL17-CCR4 axis is involved in ERK1/2 signaling and could mediate the migration and invasion of BC cells by regulating MMP13 activation. This study suggests that CCR4 might represent a promising prognostic biomarker and a potential therapeutic option for BC.