Freestanding Oxide Membranes for Epitaxial Ferroelectric Heterojunctions.

Since facile routes to fabricate freestanding oxide membranes were previously established, tremendous efforts have been made to further improve their crystallinity, and fascinating physical properties have been also reported in heterointegrated freestanding membranes. Here, we demonstrate our synthetic recipe to manufacture highly crystalline perovskite SrRuO3 freestanding membranes using new infinite-layer perovskite SrCuO2 sacrificial layers. To accomplish this, SrRuO3/SrCuO2 bilayer thin films are epitaxially grown on SrTiO3 (001) substrates, and the topmost SrRuO3 layer is chemically exfoliated by etching the SrCuO2 template layer. The as-exfoliated SrRuO3 membranes are mechanically transferred to various nonoxide substrates for the subsequent BaTiO3 film growth. Finally, freestanding heteroepitaxial junctions of ferroelectric BaTiO3 and metallic SrRuO3 are realized, exhibiting robust ferroelectricity. Intriguingly, the enhancement of piezoelectric responses is identified in freestanding BaTiO3/SrRuO3 heterojunctions with mixed ferroelectric domain states. Our approaches will offer more opportunities to develop heteroepitaxial freestanding oxide membranes with high crystallinity and enhanced functionality.

Identification of Candidate Genes for Salt Tolerance at the Seedling Stage Using Integrated Genome-Wide Association Study and Transcriptome Analysis in Rice.

Salt stress is a major constraint in rice production worldwide. Salt stress is estimated to cause annual losses of 30-50% in rice production. Discovering and deploying salt-resistance genes are the most effective ways to control salt stress. We performed a genome-wide association study (GWAS) to detect QTLs related to salt tolerance at the seedling stage using the japonica-multiparent advanced generation intercross (MAGIC) population. Four QTLs (qDTS1-1, qDTS1-2, qDTS2, and qDTS9) associated with salt tolerance were identified on chromosomes 1, 2, and 9. Among these QTLs, a novel QTL, qDTS1-2, was located between flanking SNPs (1354576 and id1028360) on chromosome 1, with the largest -log10(P) value of 5.81 and a total phenotypic variance of 15.2%. RNA-seq analysis revealed that among the seven differentially expressed genes (DEGs) commonly identified in both P6 and JM298 showing salt tolerance, two upregulated genes, Os01g0963600 (ASR transcription factor) and Os01g0975300 (OsMYB48), related to salt and drought tolerance, were also involved in the target region of qDTS1-2. The results of this study can provide insights into further understanding of salt tolerance mechanisms and developing DNA markers for marker-assisted selection (MAS) breeding to improve the salt tolerance of cultivars in rice breeding programs.

Ultrahigh dielectric permittivity in oxide ceramics by hydrogenation.

Boosting dielectric permittivity representing electrical polarizability of dielectric materials has been considered a keystone for achieving scientific breakthroughs as well as technological advances in various multifunctional devices. Here, we demonstrate sizable enhancements of low-frequency dielectric responses in oxygen-deficient oxide ceramics through specific treatments under humid environments. Ultrahigh dielectric permittivity (~5.2 × 106 at 1 Hz) is achieved by hydrogenation, when Ni-substituted BaTiO3 ceramics are exposed to high humidity. Intriguingly, thermal annealing can restore the dielectric on-state (exhibiting huge polarizability in the treated ceramics) to the initial dielectric off-state (displaying low polarizability of ~103 in the pristine ceramics after sintering). The conversion between these two dielectric states via the ambient environment-mediated treatments and the successive application of external stimuli allows us to realize reversible control of dielectric relaxation characteristics in oxide ceramics. Conceptually, our findings are of practical interest for applications to highly efficient dielectric-based humidity sensors.

A dual-center study of predictive factors for sperm retrieval through microdissection testicular sperm extraction and intracytoplasmic sperm injection outcomes in men with non-mosaic Klinefelter syndrome.

PURPOSE: This study evaluated the predictors of sperm retrieval (SR) in non-mosaic Klinefelter syndrome (KS) patients undergoing microsurgical testicular sperm extraction (mTESE). The cutoff values of the predictors of SR and overall pregnancy rates after intracytoplasmic sperm injection (ICSI) were analyzed for the positive SR (PSR) cases. MATERIALS AND METHODS: The study was a dual-center retrospective study. Overall 118 patients with KS underwent mTESE between January 2011 and July 2021. Clinicopathological factors including comorbidities, endocrine profiles, and testicular volumes were analyzed. RESULTS: A total of 58 patients showed PSR (49.2%) and 60 patients (50.8%) had negative SR (NSR). The mean overall age of the patients was 32.5 years. The NSR patients had a significantly greater prevalence of obesity, diabetes mellitus, and cerebrovascular disease. The PSR group had a significantly higher left testis mean volume (p=0.039). The differences between the two study groups regarding follicular-stimulating hormone, luteinizing hormone, and testosterone variations at 1 and 3 months after mTESE were insignificant. Preoperative mean neutrophil-to-lymphocyte ratio was significantly greater in the NSR group (p=0.011), but the platelet-to-lymphocyte ratio showed no significant difference between the two study groups. A live child birth was achieved in 53.4% of the PSR patients. Multivariate logistic analysis showed that total testicular volume >3.93 mL, left testis volume >1.79 mL, and neutrophil-to-lymphocyte ratio ≤1.82 were significantly associated with PSR. CONCLUSIONS: mTESE-ICSI is a feasible method for KS patients to have a child, and total testicular volume, left testis volume, and neutrophil-to-lymphocyte ratio might be predictors of successful SR.

Reversibly Controlled Ternary Polar States and Ferroelectric Bias Promoted by Boosting Square-Tensile-Strain.

Interaction between dipoles often emerges intriguing physical phenomena, such as exchange bias in the magnetic heterostructures and magnetoelectric effect in multiferroics, which lead to advances in multifunctional heterostructures. However, the defect-dipole tends to be considered the undesired to deteriorate the electronic functionality. Here, deterministic switching between the ferroelectric and the pinched states by exploiting a new substrate of cubic perovskite, BaZrO3 is reported, which boosts the square-tensile-strain to BaTiO3 and promotes four-variants in-plane spontaneous polarization with oxygen vacancy creation. First-principles calculations propose a complex of an oxygen vacancy and two Ti3+ ions coins a charge-neutral defect-dipole. Cooperative control of the defect-dipole and the spontaneous polarization reveals ternary in-plane polar states characterized by biased/pinched hysteresis loops. Furthermore, it is experimentally demonstrated that three electrically controlled polar-ordering states lead to switchable and nonvolatile dielectric states for application of nondestructive electro-dielectric memory. This discovery opens a new route to develop functional materials via manipulating defect-dipoles and offers a novel platform to advance heteroepitaxy beyond the prevalent perovskite substrates.

Expression of Piezo1 in the Trigeminal Neurons and in the Axons That Innervate the Dental Pulp.

Information on the neurons and axons that express the mechanosensitive channel Piezo1 and its expression in axons innervating the dental pulp may help understand the nature of the Piezo1-mediated mechanosensation and the underlying mechanism of dentin sensitivity elicited by mechanical stimuli. For this, we here investigated the neurochemical properties of the neurons in the rat trigeminal ganglion (TG) and their axons in its sensory root that express Piezo1 and the expression of Piezo1 in the rat and human dental pulp by light and electron microscopic immunohistochemistry and quantitative analysis. Piezo1 was expressed mainly in medium-sized and large TG neurons. Piezo1-immunopositive (+) neurons frequently coexpressed the marker for neurons with myelinated axons, NF200, but rarely the markers for neurons with unmyelinated axons, CGRP or IB4. In the sensory root of TG, Piezo1 was expressed primarily in small myelinated axons (Aδ, 60.2%) but also in large myelinated (Aß, 24.3%) and unmyelinated (C, 15.5%) axons. In the human dental pulp, Piezo1 was expressed in numerous NF200+ axons, which formed a network in the peripheral pulp and often "ascended" toward the dentin. Most Piezo1+ myelinated axons in the radicular pulp became unmyelinated in the peripheral pulp, where Piezo1 immunoreaction product was associated with the axonal plasma membrane, suggesting a functional role of Piezo1 in the peripheral pulp. These findings suggest that Piezo1 is involved primarily in mediating the acute pain elicited by high-threshold mechanical stimuli, and that the Piezo1-mediated dental mechanotransduction occurs primarily in the axons in the peripheral pulp.

Controlling Spin-Orbit Coupling to Tailor Type-II Dirac Bands.

NiTe2, a type-II Dirac semimetal with a strongly tilted Dirac band, has been explored extensively to understand its intriguing topological properties. Here, using density functional theory calculations, we report that the strength of the spin-orbit coupling (SOC) in NiTe2 can be tuned by Se substitution. This results in negative shifts of the bulk Dirac point (BDP) while preserving the type-II Dirac band. Indeed, combined studies using scanning tunneling spectroscopy and angle-resolved photoemission spectroscopy confirm that the BDP in the NiTe2-xSex alloy moves from +0.1 eV (NiTe2) to -0.3 eV (NiTeSe) depending on the Se concentrations, indicating the effective tunability of type-II Dirac Fermions. Our results demonstrate an approach to tailor the type-II Dirac band in NiTe2 by controlling the SOC strength via chalcogen substitution. This approach can be applicable to different types of topological materials.

Clinical Implication of Preoperative Renal Function on Oncological Outcomes in Patients with Upper Tract Urothelial Carcinoma after Radical Nephroureterectomy.

This study aims to evaluate the impact of preoperative renal function on oncological outcomes in patients with upper tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy (RNU). We performed a retrospective analysis of patients who underwent RNU between 2000 and 2012 at six academic centers. The patients were stratified into two groups based on preoperative renal function: eGFR < 60 mL/min/1.73 m2 (chronic kidney disease; CKD) and eGFR ≥ 60 mL/min/1.73 m2 (non-CKD). We investigated oncological outcomes, including overall survival, cancer-specific survival, and progression-free survival dichotomized by preoperative renal function. Multivariable Cox proportional hazards regression was used to determine if preoperative CKD was associated with oncological outcomes. In total, 1733 patients were eligible for the present study (CKD = 707 and non-CKD = 1026). Significant differences were noted in the clinical and pathologic features among the two groups, including age, sex, tumor localization, pathological T stage, tumor grade, and number of patients who received adjuvant chemotherapy. The estimated five-year overall survival (79.4 vs. 67.5%, log-rank p < 0.001), cancer-specific survival (83.5 vs. 73.6%, log-rank p < 0.001), and progression-free survival (74.6 vs. 61.5%, log-rank p < 0.001) were significantly different between the two groups, longer in the non-CKD group. Upon multivariable analysis, preoperative CKD status was associated with increased risk of overall mortality, cancer-specific mortality, and progression (p = 0.010, p = 0.016, and p = 0.008, respectively). UTUC patients with preoperative CKD had a higher risk of poor overall survival, cancer-specific survival, and progression-free survival after RNU than those without CKD.

miR-22-3p and miR-30e-5p Are Associated with Prognosis in Cervical Squamous Cell Carcinoma.

Alteration in expression of miRNAs can cause various malignant changes and the metastatic process. Our aim was to identify the miRNAs involved in cervical squamous cell carcinoma (SqCC) and metastasis, and to test their utility as indicators of metastasis and survival. Using microarray technology, we performed miRNA expression profiling on primary cervical SqCC tissue (n = 6) compared with normal control (NC) tissue and compared SqCC that had (SqC-M; n = 3) and had not (SqC-NM; n = 3) metastasized. Four miRNAs were selected for validation by qRT-PCR on 29 SqC-NM and 27 SqC-M samples, and nine metastatic lesions (ML-SqC), from a total of 56 patients. Correlation of miRNA expression and clinicopathological parameters was analyzed to evaluate the clinical impact of candidate miRNAs. We found 40 miRNAs differentially altered in cervical SqCC tissue: 21 miRNAs were upregulated and 19 were downregulated (≥2-fold, p < 0.05). Eight were differentially altered in SqC-M compared with SqC-NM samples: four were upregulated (miR-494, miR-92a-3p, miR-205-5p, and miR-221-3p), and four were downregulated (miR-574-3p, miR-4769-3p, miR-1281, and miR-1825) (≥1.5-fold, p < 0.05). MiR-22-3p might be a metastamiR, which was gradually further downregulated in SqC-NM > SqC-M > ML-SqC. Downregulation of miR-30e-5p significantly correlated with high stage, lymph node metastasis, and low survival rate, suggesting an independent poor prognostic factor.

Acoustic Anomalies and the Critical Slowing-Down Behavior of MAPbCl3 Single Crystals Studied by Brillouin Light Scattering.

Inelastic light scattering spectra of organic-inorganic halide perovskite MAPbCl3 single crystals were investigated by using Brillouin spectroscopy. Sound velocities and acoustic absorption coefficients of longitudinal and transverse acoustic modes propagating along the cubic [100] direction were determined in a wide temperature range. The sound velocities exhibited softening upon cooling in the cubic phase, which was accompanied by the increasing acoustic damping. The obtained relaxation time showed a critical slowing-down behavior, revealing the order-disorder nature of the phase transition, which is consistent with the growth of strong central peaks upon cooling toward the phase transition point. The temperature dependences of the two elastic constants C11 and C44 were obtained in the cubic phase for the first time. The comparison of C11 and C44 with those of other halide perovskites showed that C11 of MAPbCl3 is larger and C44 is slightly smaller compared to the values of MAPbBr3 and MAPbI3. It suggests that MAPbCl3 has a more compact structure (smaller lattice constant) along with stronger binding forces, causing larger C11 and bulk modulus in this compound, and that the shear rigidity is exceedingly small similar to other halide perovskites. The reported elastic constants in this study may serve as a testbed for theoretical and calculational approaches for MAPbCl3.

Template Engineering of Metal-to-Insulator Transitions in Epitaxial Bilayer Nickelate Thin Films.

Understanding metal-to-insulator phase transitions in solids has been a keystone not only for discovering novel physical phenomena in condensed matter physics but also for achieving scientific breakthroughs in materials science. In this work, we demonstrate that the transport properties (i.e., resistivity and transition temperature) in the metal-to-insulator transitions of perovskite nickelates are tunable via the epitaxial heterojunctions of LaNiO3 and NdNiO3 thin films. A mismatch in the oxygen coordination environment and interfacial octahedral coupling at the oxide heterointerface allows us to realize an exotic phase that is unattainable in the parent compound. With oxygen vacancy formation for strain accommodation, the topmost LaNiO3 layer in LaNiO3/NdNiO3 bilayer thin films is structurally engineered and it electrically undergoes a metal-to-insulator transition that does not appear in metallic LaNiO3. Modification of the NdNiO3 template layer thickness provides an additional knob for tailoring the tilting angles of corner-connected NiO6 octahedra and the linked transport characteristics further. Our approaches can be harnessed to tune physical properties in complex oxides and to realize exotic physical phenomena through oxide thin-film heterostructuring.

Effect of low protein diets added with protease on growth performance, nutrient digestibility of weaned piglets and growing-finishing pigs.

The objective of this study was to evaluate the effects of low protein diets added with protease on growth performance, nutrient digestibility, and blood profiles of weaned piglets and growing-finishing pigs. A total of 96 weaned pigs ([Yorkshire × Landrace] × Duroc) with average body weight (BW) of 6.99 ± 0.21 kg were used in a 20-week experiment. The dietary treatments were arranged in a 2 × 3 factorial design. Treatments were as follows: In phase 1 (1-2 weeks), two protein levels as high protein (HP; 19.0%), low protein (LP; 17.0%), and three protease (PT) levels (PT0, 0%; PT1, 0.3%; and PT2, 0.5%); in phase 2 (3-4 weeks), protein levels (HP, 18.05%; LP, 16.15%) and protease levels (0%, 0.3%, and 0.5%); in phase 3 (5-12 weeks), protein levels (HP, 17.1%; LP, 15.3%) and protease level (0%, 0.15%, and 0.3%); in phase 4 (13-20 weeks), protein levels (HP, 16.15%; LP, 14.45%) and protease level (0%, 0.15%, and 0.3%). At 4 weeks and 20 weeks after treatment, BW was higher (p < 0.050) in the PT2 group than PT0 group. From weeks 0 to 4, average daily gain (ADG) and feed efficiency (G/F) were higher (p = 0.006 and p = 0.014; p = 0.014 and p = 0.044, respectively) in the PT2 group than PT0 and PT1 groups. From weeks 16 to 20, ADG and G/F were higher (p < 0.001 and p = 0.009; p = 0.004 and p = 0.033, respectively) in the PT2 group than PT0 and PT1 groups. Crude protein (CP) digestibility was higher (p = 0.013, p = 0.014, and p = 0.035, respectively) in the low protein (LP) group than high protein (HP) group at weeks 4, 12, and 20. At weeks 4 and 20, the LP diet group had lower (p < 0.001 and p = 0.001, respectively) blood urea nitrogen (BUN) levels than the HP diet group. Therefore, a low CP diet added with protease could increase growth performance and CP digestibility of weaned piglets and growing-finishing pigs.

Effects of microencapsulated organic acids on growth performance, nutrient digestibility, fecal microbial counts, and blood profiles in weaning pigs.

This study was conducted to investigate the efficiency of a microencapsulated mixture of organic acids (MOA) with low protein in piglet feed on growth performance, diarrhea score, nutrient digestibility, fecal microbial counts, and blood profiles in weaning pigs. A total of 80 pigs [(Landrace × Yorkshire) × Duroc; 6.8 ± 0.48 kg] were randomly assigned to four dietary treatment groups: high protein (HP); low protein (LP); MOA1, LP + 0.2% MOA; and MOA2, LP + 0.3% MOA. The MOA2 group had higher average daily weight gains (during days 0-14 and days 0-28), diarrhea score (during days 0-14, during days 14-28 and days 0-28) and greater digestibility of dry matter (days 14 and 28) compared to the LP group (p < 0.05). However, there were no significant differences (p > 0.05) between the pigs fed diets with the MOA1 and MOA2 in blood profiles and fecal microflora. In conclusion, this study indicates that piglets fed 0.3% MOA in low protein diets maintained similar growth performance and nutrient digestibility, but alleviated the incidence of diarrhea compared to piglets fed high protein diets.

Comparison of oncologic and functional outcomes between radical nephroureterectomy and segmental ureterectomy for upper urinary tract urothelial carcinoma.

This study aims to compare oncologic and functional outcomes after radical nephroureterectomy (RNU) and segmental ureterectomy (SU) in patients with upper urinary tract urothelial carcinoma (UTUC). We retrospectively collected data on patients who underwent either RNU or SU of UTUC. Propensity score matching was performed among 394 cases to yield a final cohort of 40 RNU and 40 SU cases. Kaplan-Meier analysis and the log-rank test were used to compare overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), and intravesical recurrence-free survival (IVRFS) between the groups. We also compared the change in postoperative estimated glomerular filtration rate (eGFR). There was no significant difference in terms of CSS, PFS, and IVRFS between the RNU and SU groups, but the RNU group had a better OS than the SU group (p = 0.032). Postoperative eGFR was better preserved in the SU group than in the RNU group (p < 0.001). SU provides comparable CSS, PFS, and IVRFS for patients with UTUC compared to RNU, even in patients with advanced-stage and/or high-grade cancer. Further, SU achieves better preservation of renal function.

Development and Validation of a Method for Determining the Quercetin-3-O-glucuronide and Ellagic Acid Content of Common Evening Primrose (Oenothera biennis) by HPLC-UVD.

Toward the standardization of common evening primrose (Oenothera biennis) sprout extract (OBS-E), we aimed to obtain indicator compounds and use a validated method. HPLC-UVD allowed simultaneous quantification of the indicator compounds quercetin-3-O-glucuronide and ellagic acid. The method was validated in terms of specificity, linearity, precision, accuracy, and limit of detection/limit of quantification (LOD/LOQ). High specificity and linearity was demonstrated, with correlation coefficients of 1.0000 for quercetin-3-O-glucuronide and 0.9998 for ellagic acid. The LOD/LOQ values were 0.486/1.472 µg/mL for quercetin-3-O-glucuronide and 1.003/3.039 µg/mL for ellagic acid. Intra-day and inter-day variability tests produced relative standard deviation for each compound of <2%, a generally accepted precision criterion. High recovery rate were also obtained, indicating accuracy validation. The OBS-E prepared using various concentrations of ethanol were then analyzed. The 50% ethanol extract had highest content of quercetin-3-O-glucuronide, whereas the 70% ethanol extract possessed the lowest. However, the ellagic acid content was highest in the 70% ethanol extract and lowest in the 90% ethanol extract. Thus, quercetin-3-O-glucuronide and ellagic acid can be used industrially as indicator compounds for O. biennis sprout products, and our validated method can be used to establish indicator compounds for other natural products.

Synergism of AZD6738, an ATR Inhibitor, in Combination with Belotecan, a Camptothecin Analogue, in Chemotherapy-Resistant Ovarian Cancer.

Epithelial ovarian cancer remains the leading cause of mortality among all gynecologic malignancies owing to recurrence and ultimate development of chemotherapy resistance in the majority of patients. In the chemotherapy-resistant ovarian cancer preclinical model, we investigated whether AZD6738 (an ataxia telangiectasia and Rad3-related (ATR) inhibitor) could synergize with belotecan (a camptothecin analog and topoisomerase I inhibitor). In vitro, both chemotherapy-resistant and chemotherapy-sensitive ovarian cancer cell lines showed synergistic anti-proliferative activity with a combination treatment of belotecan and AZD6738. The combination also demonstrated synergistic tumor inhibition in mice with a chemotherapy-resistant cell line xenograft. Mechanistically, belotecan, a DNA-damaging agent, increased phospho-ATR (pATR) and phospho-Chk1 (pChk1) in consecutive order, indicating the activation of the DNA repair system. This consequently induced G2/M arrest in the cell cycle analysis. However, when AZD6738 was added to belotecan, pATR and pChk1 induced by belotecan alone were suppressed again. A cell cycle analysis in betotecan showed a sub-G1 increase as well as a G2/M decrease, representing the release of G2/M arrest and the induction of apoptosis. In ascites-derived primary cancer cells from both chemotherapy-sensitive and -resistant ovarian cancer patients, this combination was also synergistic, providing further support for our hypothesis. The combined administration of ATR inhibitor and belotecan proved to be synergistic in our preclinical model. This combination warrants further investigation in a clinical trial, with a particular aim of overcoming chemotherapy resistance in ovarian cancer.

Percutaneous Trans-splenic Obliteration for Duodenal Variceal bleeding: A Case Report.

Duodenal varices are a serious complication of portal hypertension. Bleeding from duodenal varices is rare, but when bleeding does occur, it is massive and can be fatal. Unfortunately, the optimal therapeutic modality for duodenal variceal bleeding is unclear. This paper presents a patient with duodenal variceal bleeding that was managed successfully using percutaneous trans-splenic variceal obliteration (PTVO). A 56-year-old man with a history of alcoholic cirrhosis presented with a 6-day history of melena. Emergency esophagogastroduodenoscopy revealed a large, bluish mass with a nipple sign in the second portion of the duodenum. Coil embolization of the duodenal varix was performed via a trans-splenic approach (i.e., PTVO). The patient no longer complained of melena after treatment. The duodenal varix was no longer visible at the follow-up esophagogastroduodenoscopy performed three months after PTVO. The use of PTVO might be a viable option for the treatment of duodenal variceal bleeding.

Feasibility and early toxicity of focal or partial brachytherapy in prostate cancer patients.

PURPOSE: The aim of this study was to compare short-term oncologic outcomes and toxicity of focal or partial low-dose-rate brachytherapy (focal/partial LDR-BT) with whole gland low-dose-rate brachytherapy (whole LDR-BT) in localized prostate cancer patients. MATERIAL AND METHODS: Medical records of eligible patients who underwent focal/partial LDR-BT and whole LDR-BT between 2015 and 2017 at our institution were reviewed retrospectively. Clinical characteristics and pathologic outcomes were compared between focal/partial LDR-BT group and whole LDR-BT group. Biochemical recurrence-free survival was analyzed using Kaplan-Meier method and difference between two groups was assessed with log-rank test. Genitourinary and rectal toxicity were also evaluated between the two groups. RESULTS: Of the 60 patients analyzed, 30 focal/partial LDR-BT patients and 30 whole LDR-BT brachytherapy patients were included. Relative to the whole LDR-BT group, the focal/partial LDR-BT group had significantly higher initial PSA level (p = 0.002), smaller number of implanted seeds (p < 0.001), and shorter follow-up duration (p < 0.001). There was no significant difference between the two groups with regard to prostate volume, biopsy Gleason score, and risk group stratification. The 3-year biochemical recurrence-free survival estimates for focal/partial LDR-BT group and whole LDR-BT group were 91.8% and 89.6%, respectively, which was not significantly different (p = 0.554). Genitourinary symptoms were significantly worse in whole LDR-BT group than in focal/partial LDR-BT group. The incidence of rectal toxicity was similar between two groups. CONCLUSIONS: Our findings indicate that the focal/partial LDR-BT is comparable to the whole LDR-BT with respect to short-term biochemical recurrence and toxicities.

An alternative miRISC targets a cancer-associated coding sequence mutation in FOXL2.

Recent evidence suggests that animal microRNAs (miRNAs) can target coding sequences (CDSs); however, the pathophysiological importance of such targeting remains unknown. Here, we show that a somatic heterozygous missense mutation (c.402C>G; p.C134W) in FOXL2, a feature shared by virtually all adult-type granulosa cell tumors (AGCTs), introduces a target site for miR-1236, which causes haploinsufficiency of the tumor-suppressor FOXL2. This miR-1236-mediated selective degradation of the variant FOXL2 mRNA is preferentially conducted by a distinct miRNA-loaded RNA-induced silencing complex (miRISC) directed by the Argonaute3 (AGO3) and DHX9 proteins. In both patients and a mouse model of AGCT, abundance of the inversely regulated variant FOXL2 with miR-1236 levels is highly correlated with malignant features of AGCT. Our study provides a molecular basis for understanding the conserved FOXL2 CDS mutation-mediated etiology of AGCT, revealing the existence of a previously unidentified mechanism of miRNA-targeting disease-associated mutations in the CDS by forming a non-canonical miRISC.