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Most fungal viruses are RNA viruses and no double-stranded DNA virus that infects fungi is known to date. A recent study detected DNA polymerase genes that originated from large dsDNA viruses in the genomes of basal fungi, suggestive of the existence of dsDNA viruses capable of infecting fungi. In this study, we searched for viral infection signatures in chromosome-level genome assemblies of the arbuscular mycorrhizal fungusRhizophagus irregularis. We identified a continuous 1.5 Mb putative viral region on a chromosome inR. irregularisstrain 4401. Phylogenetic analyses revealed that the viral region is related to viruses in the familyAsfarviridaeof the phylumNucleocytoviricota. Single-copy marker genes fromNucleocytoviricotawere detected as single-copy genes in the viral region. Furthermore, this viral region was absent in the genomes of four otherR. irregularisstrains and had fewer signals of fungal transposable elements than the other genomic regions. These results suggest a recent and single insertion of a large dsDNA viral genome in the genome of this fungal strain, providing strong evidence of the recent infection of the fungus by a dsDNA virus.

Urological cancers are common malignancies worldwide. Several conventional models, for example, two-dimensional cell culture and animal models have been used for decades to study tumor genetics. Nonetheless, these methods have limitations in reflecting the real tumor microenvironment in vivo, thereby hindering the development of anti-cancer therapeutic agents. Recently, three-dimensional culture models have gained attention because they can overcome the drawbacks of traditional methods. Above all, three-dimensional organoid models are able to mimic the tumor microenvironment in human bodies more closely as they are able to demonstrate the interactions between cells and extracellular matrix. This type of model has therefore extended our understanding of urological cancers. Tumor cells in organoid models can also be co-cultured with other cellular components, such as peripheral blood lymphocytes, and allow further understanding of the effect of tumor microenvironments on tumor growth. Furthermore, organoid models allow a prolonged culturing period, therefore, tumor evolution, progression and maintenance can also be assessed. Organoid models can be derived from each specific patient, and this facilitates investigation of individual cancer-specific mutations and their subtypes. As a result, the development of personalized medication targeting the signaling pathways or biomolecules of interest will be possible. In the present review, we summarize the development and applications of three-dimensional organoid cultures in urological cancers, mainly focusing on prostate, urinary bladder and kidney cancers, and assess the future prospects of this model.

In this paper, indium tin oxide/silver indium/indium tin oxide (ITO/AgIn/ITO) composite films were deposited on glass substrates by magnetron sputtering. The effects of the sputtering temperature on the optical and electrical properties of the composite films were systematically investigated. The ITO/AgIn/ITO composite films deposited at sputtering temperatures of 25 °C and 100 °C demonstrated a high reflectivity of 95.3% at 550 nm and a resistivity of about 6.8–7.3 μΩ·cm. As the sputtering temperature increased, the reflectivity decreased and the resistivity increased slightly. The close connection between microstructure and surface morphology and the optical and electrical properties of the composite films was further illustrated by scanning electron microscopy imaging and atomic force microscopy imaging. It is shown that the ITO/AgIn/ITO thin films have a promising application for high-reflectivity anodes.

The interface between metal nanoparticles (NPs) and support plays a vital role in catalysis because both electron and atom exchanges occur across the metal-support interface. However, the rational design of interfacial structure facilitating the charge transfer between the neighboring parts remains a challenge. Herein, a guided nucleation strategy based on redox reaction between noble metal precursor and support-surface is introduced to construct epitaxial interfaces between Pt NPs and CeO2 support. The Pt/CeO2 catalyst exhibits near room temperature catalytic activity for CO oxidation that is benefited from the well-defined interface structure facilitating charge transfer from CeO2 support to Pt NPs. Meanwhile, this general approach based on support-surface-induced-nucleation was successfully extended to synthesize Pd and Cu nanocatalysts on CeO2, demonstrating its universal and feasible characteristics. This work is an important step towards developing highly active supported metal catalysts by engineering their interfaces.

During the launching of spacecraft, the on-board devices will undergo a series of pyroshock environments. In order to verify the reliability of these devices under these pyroshock environments, all of them are needed to take the shock test before launching. This paper has carried out an in-depth research on the simulation method of the pyroshock based on the true explosive excitation. In this study, a simulator containing multiple adjustment parameters is presented and the safety is considered by the design of the protective cover. And the working process of this setup is simulated with the explicit dynamic codes LS-DYNA. What’s more, the effects of the adjustment parameters on the three factors of shock Response Spectrum (SRS) of the resonant board are explored carefully. The rules achieved in this paper are verified by a typical example. The results indicate that the improved simulator can avoid the danger of explosive and make full use of the advantage of actual explosive excitation. And the test condition can be quickly realized at the simulator according to the effect rules of the three adjustable parameters. Keywords: Adjustable parameters, Maximum Expected Flight Environment (MEFE), Protective cover, Pyroshock, Shock Response Spectrum (SRS)

© 2022 Editorial Office of Asian Journal of UrologyObjective: To scrutinize the definitions of minimal invasive surgical therapy (MIST) and to investigate urologists’ knowledge, attitude, and practices for benign prostatic obstruction surgeries. Methods: A 36-item survey was developed with a Delphi method. Questions on definitions of MIST and attitude and practices of benign prostatic obstruction surgeries were included. Urologists were invited globally to complete the online survey. Consensus was achieved when more than or equal to 70% responses were \"agree or strongly agree\" and less than or equal to 15% responses were \"disagree or strongly disagree\" (consensus agree), or when more than or equal to 70% responses were \"disagree or strongly disagree\" and less than or equal to 15% responses were \"agree or strongly agree\" (consensus disagree). Results: The top three qualities for defining MIST were minimal blood loss (n=466, 80.3%), fast post-operative recovery (n=431, 74.3%), and short hospital stay (n=425, 73.3%). The top three surgeries that were regarded as MIST were Urolift® (n=361, 62.2%), Rezum® (n=351, 60.5%), and endoscopic enucleation of the prostate (EEP) (n=332, 57.2%). Consensus in the knowledge section was achieved for the superiority of Urolift®, Rezum®, and iTIND® over transurethral resection of the prostate with regards to blood loss, recovery, day surgery feasibility, and post-operative continence. Consensus in the attitudes section was achieved for the superiority of Urolift®, Rezum®, and iTIND® over transurethral resection of the prostate with regards to blood loss, recovery, and day surgery feasibility. Consensus on both sections was achieved for EEP as the option with the better symptoms and flow improvement, lower retreatment rate, and better suitable for prostate more than 80 mL. Conclusion: Minimal blood loss, fast post-operative recovery, and short hospital stay were the most important qualities for defining MIST. Urolift®, Rezum®, and EEP were regarded as MIST by most urologists.

The 2D scanning reflector (2DSR) has been widely used in various important opto-mechanical systems. The pointing error of the mirror normal of the 2DSR will greatly affect the optical axis pointing accuracy. In this work, a digital calibration method for the pointing error of the mirror normal of the 2DSR is researched and verified. At first, the error calibration method is proposed based on the datum, which consists of a high-precision two-axis turntable and the photoelectric autocollimator. All the error sources, including the assembly errors and the datum errors in the calibration are analyzed comprehensively. Then the pointing models of the mirror normal are derived from the 2DSR path and the datum path by using the quaternion mathematical method. Additionally, the pointing models are linearized by the Taylor series first-order approximation of the error parameter trigonometric function items. The solution model of the error parameters is further established by using the least square fitting method. In addition, the procedure of the datum establishment is introduced in detail to strictly control the datum error to be small enough, and the calibration experiment is carried out subsequently. At last, the errors of the 2DSR are calibrated and discussed. The results show that the pointing error of the mirror normal of the 2DSR decreases from 365.68 to 6.46 arc seconds after the error compensation. The consistency of the error parameters of the 2DSR calibrated by digital calibration and physical calibration verifies the effectiveness of the digital calibration method proposed in this paper.

Carbon–selenium composite positive electrode (CSs@Se) is engineered in this project using a melt diffusion approach with glucose as a precursor, and it demonstrates good electrochemical performance for lithium–selenium batteries. X-ray diffraction (XRD) and scanning electron microscopy (SEM) with EDS analysis are used to characterize the newly designed CSs@Se electrode. To complete the evaluation, electrochemical characterization such as charge–discharge (rate performance and cycle stability), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) tests are done. The findings show that selenium particles are distributed uniformly in mono-sized carbon spheres with enormous surface areas. Furthermore, the charge–discharge test demonstrates that the CSs@Se cathode has a rate performance of 104 mA h g−1 even at current density of 2500 mA g−1 and can sustain stable cycling for 70 cycles with a specific capacity of 270 mA h g−1 at current density of 25 mA g−1. The homogeneous diffusion of selenium particles in the produced spheres is credited with an improved electrochemical performance.

Introduction Traditional intravesical chemotherapy instillations under room temperature post trans-urethral resection (TUR) of non-muscle invasive bladder cancer (NMIBC) have lower efficacies than maintenance BCG installations. Intravesical chemo-hyperthermia (CHT) at higher temperatures is developed to improve the efficacy of chemotherapy instillation. This systematic review aims to compare the use of CHT and BCG instillation post-TUR. Method The protocol of this review is registered on PROSPERO(CRD42020223277). A comprehensive literature search was performed on Medline, EMBASE, and Cochrane CENTRAL to identify studies comparing CHT and BCG post-TUR for intermediate- or high-risk NMIBC. Primary outcomes include recurrence-free survival (RFS) and progression-free survival (PFS). Secondary outcomes include adverse events (AE). Results From 2,375 identified records, four randomised control trials incorporating 327 patients were included for meta-analysis. The use of CHT was found to be non-inferior to BCG in RFS, PFS and AEs (Grades 1-3) (p > 0.05). Sensitivity analysis, excluding patients with BCG failures, show 24-36 months recurrence rate to be significantly lower in CHT group (RR 0.64, 95% CI 0.42-0.98, p = 0.04) compared to the BCG group. In patients without carcinoma in situ (CIS), RFS is also significantly better in CHT patients (HR 0.52, 95% CI 0.32- 0.85, p Conclusions In well-selected patients, intravesical CHT has superior oncological outcomes and non-inferior safety profile when compared to BCG maintenance therapy for patients with intermediate- and high-risk NMIBC. CHT is a possible alternative treatment during BCG shortage.

In order to solve the failure of traditional methods in the response prediction for the complex spacecraft under the wide frequency shock load, this paper provides the FE-SEA (Finite Element-Statistical Energy Analysis) hybrid modeling technique to improve the virtual mode synthesis and simulation (VMSS). Taking the L-shape typical structure as an example, the research is developed through the numerical analysis and experiment verification. In the FE-SEA hybrid model of the typical structure, the two honeycomb boards which have a higher modal density are built as the SEA model, while the connection beam that has a larger stiffness is established as FE model. And then the hybrid model is computed with the VMSS code, giving the transient response results. A shock experiment for the typical structure is carried out to verify the correctness of the methodology above. The results indicate that the numerical results have the similar trend and magnitudes with the ones of the experiment in time domain, and the shock response spectrum (SRS) of the numerical results can realize the ±6 dB tolerance limit compared with the experiment results. This paper finds that the FE-SEA hybrid modeling techniques for the typical structure can effectively overcome the problem of the dynamic differences between the substructures under the excitation of shock load, and the combination of FE-SEA and VMSS has the ability to predict the shock responses of the typical structure accurately. The research methods and conclusions achieved in this paper are expected to further extend to the shock response calculation of the complex spacecraft structures.

This paper mainly discusses the shock environment prediction of the satellite in the process of satellite-rocket separation. At first, the field near to the shock source (near-field) that contains the pyrotechnic separation nut, satellite joint and rocket joint is researched with separation shock experiment and explicit dynamic code LS-DYNA. And then, the satellite model (far-field) is introduced. The force curve at the interface of satellite joint and the adjacent angle steel in vertical direction is extracted and used as the input of shock environment of satellite. Furthermore, the shock environment of the bottom panel and the side panel of the satellite in the flexure direction are computed by Virtual Mode Synthesis Simulation (VMSS). The results are compared with the ones of Finite Element Method (FEM). At last, the deficiencies of VMSS on the shock environment prediction of the satellite panel in the extension and shear directions are revealed since they do not contain enough modal number. The completed shock environment prediction method proposed in this paper is expected to provide a reference for the rapid and accurate computation of the shock environment at the initial stage of satellite structure design.

Although the silicon oxide (SiO2) as an anode material shows potential and promise for lithium-ion batteries (LIBs), owing to its high capacity, low cost, abundance, and safety, severe capacity decay and sluggish charge transfer during the discharge–charge process has caused a serious challenge for available applications. Herein, a novel 3D porous silicon oxide@Pourous Carbon@Tin (SiO2@Pc@Sn) composite anode material was firstly designed and synthesized by freeze-drying and thermal-melting self-assembly, in which SiO2 microparticles were encapsulated in the porous carbon as well as Sn nanoballs being uniformly dispersed in the SiO2@Pc-like sesame seeds, effectively constructing a robust and conductive 3D porous Jujube cake-like architecture that is beneficial for fast ion transfer and high structural stability. Such a SiO2@Pc@Sn micro-nano hierarchical structure as a LIBs anode exhibits a large reversible specific capacity ~520 mAh·g−1, initial coulombic efficiency (ICE) ~52%, outstanding rate capability, and excellent cycling stability over 100 cycles. Furthermore, the phase evolution and underlying electrochemical mechanism during the charge–discharge process were further uncovered by cyclic voltammetry (CV) investigation.

The broadband perfect absorption of visible light is of great significance for solar cells and photodetectors. The realization of a two-dimensional broadband perfect absorber in the visible range poses a formidable challenge with regard to improving the integration of optical systems. In this paper, we numerically demonstrate a broadband perfect absorber in the visible range from 400 nm to 700 nm based on metasurface composite structures. Simulation results show that the average absorptance is ~95.7% due to the combination of the intrinsic absorption of the lossy metallic material (Au) and the coupling resonances of the multi-sized resonators. The proposed perfect absorber may find potential applications in photovoltaics and photodetection.

To evaluate and compare the incidences of post-operative pelvic pain (PPP) in patients undergoing ablation, enucleation and conventional transurethral resection of the prostate (TURP). A systematic review and meta-analysis was conducted according to the PRISMA guidelines. Using MEDLINE via PubMed and Cochrane CENTRAL, randomised control trials (RCTs) and observational studies reporting PPP rates post-ablation, enucleation or TURP were identified. The risk of biases (RoB) in RCTs and observation studies were assessed using the Cochrane RoB1.0 tool and the Newcastle–Ottawa Scale, respectively. 62 studies were included for qualitative analysis, while 51 of them reported number of patients with PPP post-intervention. Three observational studies and 13 RCTs compared the rates of PPP in patients undergoing ablation, enucleation or TURP. The most reported types of PPP are dysuria, abdominal pain and irritative symptoms. The pooled incidence of PPP at 1-month follow-up in patients undergoing ablation, enucleation and TURP were 0.15 (95% CI 0.10–0.22), 0.09 (95% CI 0.04–0.19 and 0.10 (95% CI 0.06–0.15), respectively. PPP is no longer prevalent at 3-months and onwards post-operatively. Ablation is associated with a higher risk of PPP than enucleation (RR 2.19, 95% CI 1.04–4.62) and TURP (RR 2.40, 95% CI 1.03–5.62) in observational studies but not RCTs; and there were no significant differences in the rates of PPP upon comparison of other modalities. PPP is common after transurethral benign prostatic hyperplasia surgery. Patients undergoing ablation had a higher rate of post-intervention PPP than those undergoing enucleation and TURP in observational studies.

This paper establishes a finite element model of pyrotechnic separation nuts and simulates the whole separation process based on the explicit dynamic codes LS-dyna with Arbitrary Lagrange-Euler (ALE) algorithm. The separation shock generated in the unlocking process is analyzed in detail and the results reveal that the pyrotechnic explosion shock and strain energy shock are two sources for the whole separation shock. Besides that, the influence of prestress on the separation shock and its two shock sources is also researched. The results show that the prestress could strengthen all three shocks, especially the strain energy release shock. This paper also compares the shock response spectrum (SRS) of the three shocks and finds that the SRS of separation shock is equal to the envelope of the SRS of pyrotechnic explosion shock and strain energy release shock. In the model of this paper, the pyrotechnic explosion shock plays a dominant role in the frequency range of 100 Hz to 10 KHz. The conclusions got in this work are helpful to insight the mechanism of separation shock and can provide a reference for the design of separation nuts.

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.

Bladder pain is a prominent symptom of interstitial cystitis/painful bladder syndrome. Hydrogen sulfide (H2S) generated by cystathionine β-synthase (CBS) or cystathionine γ-lyase (CSE) facilitates bladder hypersensitivity. We assessed involvement of the H2S pathway in protease-activated receptor 4 (PAR4)-induced bladder pain. A bladder pain model was induced by intravesical instillation of PAR4-activating peptide in mice. The role of H2S in this model was evaluated by intraperitoneal preadministration of d,l-propargylglycine (PAG), aminooxyacetic acid (AOAA), or S-adenosylmethionine or the preintravesical administration of NaHS. SV-HUC-1 cells were treated in similar manners. Assessments of CBS, CSE, and macrophage migration inhibitory factor (MIF) expression, bladder voiding function, bladder inflammation, H2S production, and referred bladder pain were performed. The CSE and CBS pathways existed in both mouse bladders and SV-HUC-1 cells. H2S signaling was upregulated in PAR4-induced bladder pain models, and H2S-generating enzyme activity was upregulated in human bladders, mouse bladders, and SV-HUC-1 cells. Pretreatment with AOAA or NaHS inhibited or promoted PAR4-induced mechanical hyperalgesia, respectively; however, PAG only partially inhibited PAR4-induced bladder pain. Treatment with PAG or AOAA decreased H2S production in both mouse bladders and SV-HUC-1 cells. Pretreatment with AOAA increased MIF protein levels in bladder tissues and cells, whereas pretreatment with NaHS lowered MIF protein levels. Bladder pain triggered by the H2S pathway was not accompanied by inflammation or altered micturition behavior. Thus endogenous H2S generated by CBS or CSE caused referred hyperalgesia mediated through MIF in mice with PAR4-induced bladder pain, without causing bladder injury or altering micturition behavior.

Although silicon oxide (SiO) as an anode material shows significant potential for application in lithium-ion batteries (LIBs) due to its high capacity, low cost, abundance, and adequate safety characteristics, severe capacity decay and sluggish charge transfer during discharge-charge processes limit its application. Herein, a novel strategy for preparing a ternary SiO@Pc@Ge composite has been developed using self-assembly via freeze drying and thermal melting. A robust and interconnected SiO@Pc frame provides sufficient channels for charge transfer and adequate number of pores for electrolyte infiltration. The in-situ assembled Ge nanoparticles are evenly dispersed in the SiO@Pc matrix like sesame seeds, augmenting the electrochemical activity of SiO. The SiO@Pc@Ge composite with a significant mass ratio delivers a high discharge capacity of 980.5 mA h g−1 in the initial 100 cycles at 100 mA g−1 and an excellent capacity retention of 90%, while exhibiting a superior rate capability of 627.8 mA h g−1 at 1400 mA g−1. Furthermore, the phase evolution and underlying Li storage mechanism during the charge-discharge process are further revealed via XPS and CV investigations, which indicate that the Li-ion kinetics is enhanced in the optimized samples. Our method provides novel insights into the utilization of low-cost and environmentally benign materials for fabricating high-performance energy devices through a simple and feasible procedure.

This study is to clarify the prognostic value of preoperative plasma fibrinogen and serum albumin level, as known as FA score, in a cohort of Chinese patients with upper urinary tract urothelial carcinoma (UTUC). We retrospectively evaluated clinicopathological data on 169 patients who underwent surgery between 2006 and 2013. The FA score was calculated based on cutoff values of 3.53g/L for fibrinogen and 43.56 g/L for albumin. Overall survival and cancer specific survival was assessed using the Kaplan-Meier method and the equivalences of the curves were tested by log-rank tests. The Cox proportional hazards regression model was applied in univariate and multivariate analyses. In univariate analysis, tumor size, tumor grade, pathological T stage and FA score were significantly associated with overall survival and cancer specific survival, and multivariate Cox proportional hazards regression analysis identified FA score (score 1: HR=3.486, 95%CI 1.358-8.948, p=0.009; HR=3.485, 95%CI 1.363-8.913, p=0.009, respectively; score 2: HR=5.509, 95%CI 2.144-14.158, p

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

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.

Background Bladder cancer (BC) is the most common cancer of the urinary tract and invariably predicts a poor prognosis. In this study, we found a reliable gene signature and potential biomarker for predicting clinical prognosis. Methods The gene expression profiles were obtained from the GEO database. By performing GEO2R analysis, numerous differentially expressed genes (DEGs) were found. Three different microarray datasets were integrated in order to more precisely identify up-expression genes. Functional analysis revealed that these genes were mainly involved in cell cycle, DNA replication and metabolic pathways. Results Based on protein-protein interactome (PPI) networks that were identified in the current study and previous studies, we focused on KIF15 for further study. The results showed that KIF15 promotes BC cell proliferation via the MEK -ERK pathway, and Kaplan‐Meier survival analysis revealed that KIF15 expression was an independent prognostic risk factor in BC patients. Conclusion KIF15 may represent a promising prognostic biomarker and a potential therapeutic option for BC.