Growth factors with valproic acid restore injury-impaired hearing by promoting neuronal regeneration.

Spiral ganglion neurons (SGNs) are primary auditory neurons in the spiral ganglion that transmit sound information from the inner ear to the brain and play an important role in hearing. Impairment of SGNs causes sensorineural hearing loss (SNHL), and it has been thought until now that SGNs cannot be regenerated once lost. Furthermore, no fundamental therapeutic strategy for SNHL has been established other than inserting devices such as hearing aids and cochlear implants. Here we show that the mouse spiral ganglion contains cells that are able to proliferate and indeed differentiate into neurons in response to injury. We suggest that SRY-box transcription factor 2/SRY-box transcription factor 10-double-positive (Sox2/Sox10-double-positive) Schwann cells sequentially started to proliferate, lost Sox10 expression, and became neurons, although the number of new neurons generated spontaneously was very small. To increase the abundance of new neurons, we treated mice with 2 growth factors in combination with valproic acid, which is known to promote neuronal differentiation and survival. This treatment resulted in a dramatic increase in the number of SGNs, accompanied by a partial recovery of the hearing loss induced by injury. Taken together, our findings offer a step toward developing strategies for treatment of SNHL.

Triple-negative breast cancer on contrast-enhanced MRI and synthetic MRI: A comparison with non-triple-negative breast carcinoma.

PURPOSE: This study aimed to compare the characteristics of triple-negative breast cancer (TNBC) with non-TNBC on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and synthetic MRI. METHOD: This retrospective study included 79 patients with histopathologically proven breast cancer (TNBC: 16, non-TNBC: 63) who underwent synthetic MRI. Using synthetic MR images, we obtained T1 and T2 relaxation times in breast lesions before (Pre-T1, Pre-T2, Pre-PD) and after (Gd-T1, Gd-T2, Gd-PD) contrast agent injection. Subsequently, we calculated the ΔT1 (Pre-T1 - Gd-T1), ΔT2 (Pre-T2 - Gd-T2), Pre-T1/T2, and Gd-T1/T2. We compared the aforementioned quantitative values, as well as several morphologic features between TNBCs and non-TNBCs that were identified on DCE-MRI. RESULTS: The multivariate analyses revealed that the Pre-T2 (P = 0.037) and the presence of rim enhancement (P-RIM) (P = 0.034) were significant and independent predictors of TNBC. The area under the receiver operating characteristics curve for all breast cancers was greater when a combination of Pre-T2 and P-RIM (Pre-T2＋P-RIM; Method 3, AUC (area under the curve) = 0.858) was used to distinguish between TNBCs and non-TNBCs versus the use of either Pre-T2 alone (Method 1, AUC = 0.786) or P-RIM alone (Method 2, AUC = 0.747). CONCLUSIONS: Pre-T2 obtained using synthetic MRI and P-RIM identified on DCE-MRI allowed the differentiation between TNBCs and non-TNBCs. However, these results are preliminary and need to be verified by further studies.

MeCP2 controls neural stem cell fate specification through miR-199a-mediated inhibition of BMP-Smad signaling.

Rett syndrome (RTT) is a severe neurological disorder, with impaired brain development caused by mutations in MECP2; however, the underlying mechanism remains elusive. We know from previous work that MeCP2 facilitates the processing of a specific microRNA, miR-199a, by associating with the Drosha complex to regulate neuronal functions. Here, we show that the MeCP2/miR-199a axis regulates neural stem/precursor cell (NS/PC) differentiation. A shift occurs from neuronal to astrocytic differentiation of MeCP2- and miR-199a-deficient NS/PCs due to the upregulation of a miR-199a target, Smad1, a downstream transcription factor of bone morphogenetic protein (BMP) signaling. Moreover, miR-199a expression and treatment with BMP inhibitors rectify the differentiation of RTT patient-derived NS/PCs and development of brain organoids, respectively, suggesting that facilitation of BMP signaling accounts for the impaired RTT brain development. Our study illuminates the molecular pathology of RTT and reveals the MeCP2/miR-199a/Smad1 axis as a potential therapeutic target for RTT.

Enhanced Masses on Contrast-Enhanced Breast: Differentiation Using a Combination of Dynamic Contrast-Enhanced MRI and Quantitative Evaluation with Synthetic MRI.

BACKGROUND: The addition of synthetic MRI might improve the diagnostic performance of dynamic contrast-enhanced MRI (DCE-MRI) in patients with breast cancer. PURPOSE: To evaluate the diagnostic value of a combination of DCE-MRI and quantitative evaluation using synthetic MRI for differentiation between benign and malignant breast masses. STUDY TYPE: Retrospective, observational. POPULATION: In all, 121 patients with 131 breast masses who underwent DCE-MRI with additional synthetic MRI were enrolled. FIELD STRENGTH/SEQUENCE: 3.0 Tesla, T1 -weighted DCE-MRI and synthetic MRI acquired by a multiple-dynamic, multiple-echo sequence. ASSESSMENT: All lesions were differentiated as benign or malignant using the following three diagnostic methods: DCE-MRI type based on the Breast Imaging-Reporting and Data System; synthetic MRI type using quantitative evaluation values calculated by synthetic MRI; and a combination of the DCE-MRI + Synthetic MRI types. The diagnostic performance of the three methods were compared. STATISTICAL TESTS: Univariate (Mann-Whitney U-test) and multivariate (binomial logistic regression) analyses were performed, followed by receiver-operating characteristic curve (AUC) analysis. RESULTS: Univariate and multivariate analyses showed that the mean T1 relaxation time in a breast mass obtained by synthetic MRI prior to injection of contrast agent (pre-T1 ) was the only significant quantitative value acquired by synthetic MRI that could independently differentiate between malignant and benign breast masses. The AUC for all enrolled breast masses assessed by DCE-MRI + Synthetic MRI type (0.83) was significantly greater than that for the DCE-MRI type (0.70, P < 0.05) or synthetic MRI type (0.73, P < 0.05). The AUC for category 4 masses assessed by the DCE-MRI + Synthetic MRI type was significantly greater than that for those assessed by the DCE-MRI type (0.74 vs. 0.50, P < 0.05). DATA CONCLUSION: A combination of synthetic MRI and DCE-MRI improves the accuracy of diagnosis of benign and malignant breast masses, especially category 4 masses. Level of Evidence 4 Technical Efficacy Stage 2 J. MAGN. RESON. IMAGING 2021;53:381-391.

Dual-energy computed tomography for evaluation of breast cancer: value of virtual monoenergetic images reconstructed with a noise-reduced monoenergetic reconstruction algorithm.

PURPOSE: To evaluate the image quality and lesion visibility of virtual monoenergetic images (VMIs) reconstructed using a new monoenergetic reconstruction algorithm (nMERA) for evaluation of breast cancer. MATERIALS AND METHODS: Forty-two patients with 46 breast cancers who underwent 4-phasic breast contrast-enhanced computed tomography (CT) using dual-energy CT (DECT) were enrolled. We selected the peak enhancement phase of the lesion in each patient. The selected phase images were generated by 120-kVp-equivalent linear blended (M120) and monoenergetic reconstructions from 40 to 80 keV using the standard reconstruction algorithm (sMERA: 40, 50, 60, 70, 80) and nMERA (40 +, 50 +, 60 +, 70 +, 80 +). The contrast-to-noise ratio (CNR) was calculated and objectively analyzed. Two independent readers subjectively scored tumor visibility and image quality each on a 5-point scale. RESULTS: The CNR at 40 + and tumor visibility scores at 40 + and 50 + were significantly higher than those on M120. The CNR at 50 + was not significantly different from that on M120. However, the overall image quality score at 40 + was significantly lower than that at 50 + and on M120 (40 + vs M120, P < 0.0001 and 40 + vs 50 +, P = 0.0001). CONCLUSIONS: VMI reconstructed with nMERA at 50 keV is preferable for evaluation of patients with breast cancer.

DELLA-dependent and -independent gibberellin signaling.

DELLA proteins act as negative regulators in gibberellin (GA) signal transduction. GA-induced DELLA degradation is a central regulatory system in GA signaling pathway. Intensive studies have revealed the degradation mechanism of DELLA and the functions of DELLA as a transcriptional regulator. Meanwhile, recent studies suggest the existence of a DELLA-independent GA signaling pathway. In this review, we summarized the DELLA-independent GA signaling pathway together with the well-analyzed DELLA-dependent pathway.

Gibberellin Induces an Increase in Cytosolic Ca2+ via a DELLA-Independent Signaling Pathway.

DELLA proteins play a central role in gibberellin (GA) signaling. GA triggers DELLA degradation via the ubiquitin-proteasome pathway, thereby promoting plant growth. An increase in cytosolic Ca2+ ([Ca2+]cyt) was observed previously after several hours of GA application. Recent studies also suggest the existence of a DELLA-independent GA response. However, the effect of DELLA on the GA-induced increase in [Ca2+]cyt remains unknown. This study reexamined the effects of GAs on [Ca2+]cyt using the Ca2+ sensor protein aequorin in Arabidopsis (Arabidopsis thaliana). [Ca2+]cyt increased within a few minutes of GA treatment, even in transgenic plants expressing a mutated degradation-resistant version of REPRESSOR OF ga1-3 and in della pentuple mutant plants. In addition, it was also revealed that Ca2+ is not involved in DELLA degradation. These results suggest that the GA-induced increase in [Ca2+]cyt occurs via a DELLA-independent pathway, providing important information on the GA signaling network.

Effect of stone Spa bathing and hot-spring bathing on pulse wave velocity in healthy, late middle-aged females.

OBJECTIVES: The purpose of this study was to clarify the effect of stone spa bathing (Ganban-yoku) and hot-spring bathing on brachial-ankle pulse wave velocity (baPWV) in healthy, late middle-aged females. METHODS: The subjects were 13 females (mean age, 47.3 years). The skin and tympanic temperatures, blood pressure, and baPWV were measured before and after stone spa bathing and hot-spring bathing. For the stone spa bathing, the subjects lay down three times for approximately 10 min each time over warm stone beds. RESULTS: Although body weight showed no change after the hot-spring bathing, it significantly increased after the stone spa bathing. The increase was significantly related to the amount of water intake. The skin and tympanic temperatures increased to a smaller degree after the stone spa bathing than after the hot-spring bathing. The diastolic blood pressure decreased to a smaller degree after the stone spa bathing. BaPWV showed no significant change after bathing both in the stone spa and in the hot-spring. The results of multiple regression analysis showed that the factors significantly related to the change in baPWV after the stone spa bathing were the changes in skin and tympanic temperatures and habit of smoking, and that after the hot-spring bathing was the change in skin temperature. CONCLUSIONS: The results suggest that, compared with the hot-spring bathing, stone spa bathing causes less strain on the body. The stone spa bathing and hot-spring bathing showed no marked effect on baPWV. However, there is a possibility that the stone spa bathing may be used as a load for investigating arterial stiffness.