Hydrogen sulfide antagonizes cytokinin to change root system architecture through persulfidation of CKX2 in Arabidopsis.

Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule, which has been shown to play an important role in plant growth and development by coupling with various phytohormones. However, the relationship between H2S and cytokinin (CTK) and the mechanisms by which H2S and CTK affect root growth remain poorly understood. Endogenous CTK was analyzed by UHPLC-ESI-MS/MS. Persulfidation of cytokinin oxidase/dehydrogenases (CKXs) was analyzed by mass spectrometry (MS). ckx2/CKX2wild-type (WT), OE CKX2 and ckx2/CKX2Cys(C)62alanine(A) transgenic lines were isolated with the ckx2 background. H2S is linked to CTK content by CKX2, which regulates root system architecture (RSA). Persulfidation at cysteine (Cys)62 residue of CKX2 enhances CKX2 activity, resulting in reduced CTK content. We utilized 35S-LCD/oasa1 transgenic lines to investigate the effect of endogenous H2S on RSA, indicating that H2S reduces the gravitropic set-point angle (GSA), shortens root hairs, and increases the number of lateral roots (LRs). The persulfidation of CKX2Cys62 changes the elongation of cells on the upper and lower flanks of LR elongation zone, confirming that Cys62 of CKX2 is the specificity target of H2S to regulate RSA in vivo. In conclusion, this study demonstrated that H2S negatively regulates CTK content and affects RSA by persulfidation of CKX2Cys62 in Arabidopsis thaliana.

Risk factors affecting long-term efficacy of ultrasound-guided high-intensity focused ultrasound treatment for multiple uterine fibroids.

OBJECTIVES: To investigate the long-term efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for multiple uterine fibroids and the factors associated with recurrence. MATERIALS AND METHODS: Five hundred and forty-nine patients with multiple uterine fibroids treated with USgHIFU from June 2017 to June 2019 were retrospectively analyzed. The Pictorial Blood Loss Assessment Chart (PBAC) was used to assess menstrual blood loss. The patients were asked to undergo pre- and post-USgHIFU magnetic resonance imaging (MRI) and complete routine follow-up after USgHIFU. Cox regression analysis was used to investigate the risk factors associated with recurrence. RESULTS: The median number of fibroids per patient was 3 (interquartile range: 3-4), and a total of 1371 fibroids were treated. Among them, 446 patients completed 3 years follow-up. Recurrence, defined as PBAC score above or equal to 100 and/or the residual fibroid volume increased by 10%, was detected in 90 patients within 3 years after USgHIFU, with a cumulative recurrence rate of 20.2% (90/446). The multi-factor Cox analysis showed that age was a protective factor for recurrence. Younger patients have a greater chance of recurrence than older patients. Mixed hyperintensity of fibroids on T2WI and treatment intensity were risk factors for recurrence. Patients with hyperintense uterine fibroids and treated with lower treatment intensity were more likely to experience recurrence than other patients after USgHIFU. No major adverse effects occurred. CONCLUSIONS: USgHIFU can be used to treat multiple uterine fibroids safely and effectively. The age, T2WI signal intensity and treatment intensity are factors related to recurrence.

Ginsenosides Rg1 and Rg2 Activate Autophagy and Attenuate Oxidative Stress in Neuroblastoma Cells Overexpressing Aß(1-42).

Alzheimer's disease is a neurodegeneration with protein deposits, altered proteolysis, and inflammatory and oxidative processes as major hallmarks. Despite the continuous search for potential therapeutic treatments, no cure is available to date. The use of natural molecules as adjuvants in the treatment of Alzheimer's disease is a very promising strategy. In this regard, ginsenosides from ginseng root show a variety of biological effects. Here, we dissected the role of ginsenosides Rg1 and Rg2 in modulating autophagy and oxidative stress in neuroblastoma cells overexpressing Aß(1-42). Key hallmarks of these cellular processes were detected through immunomethods and fluorometric assays. Our findings indicate that ginsenosides are able to upregulate autophagy in neuronal cells as demonstrated by increased levels of LC3II and Beclin-1 proteins and decreased amounts of p62. Simultaneously, an activation of lysosomal hydrolases was observed. Furthermore, autophagy activation promoted the clearance of Aß(1-42). Rg1 and Rg2 also reduced oxidative stress sources and macromolecule oxidation, promoting NRF2 nuclear translocation and the expression of antioxidant enzymes. Our data further clarify the mechanisms of action of Rg1 and Rg2, indicating new insights into their role in the management of disorders like Alzheimer's disease.

Non-contrast enhanced MRI for efficiency evaluation of high-intensity focused ultrasound in adenomyosis ablation.

OBJECTIVE: To investigate the value of T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) in evaluating the therapeutic effect of high-intensity focused ultrasound (HIFU) in adenomyosis ablation. MATERIAL AND METHODS: One hundred eighty-nine patients with adenomyosis were treated with HIFU. The ablation areas on T2WI and DWI sequences were classified into different types: type I, relatively ill-defined rim or unrecognizable; subtype IIa, well-defined rim with hyperintensity; subtype IIb, well-defined rim with hypointensity. The volume of ablation areas on T2WI (VT2WI) and DWI (VDWI) was measured and compared with the non-perfused volume (NPV), and linear regression was conducted to analyze their correlation with NPV. RESULTS: The VT2WI of type I and type II (subtype IIa and subtype IIb) were statistically different from the corresponding NPV (p = 0.004 and 0.024, respectively), while no significant difference was found between the VDWI of type I and type II with NPV (p = 0.478 and 0.561, respectively). In the linear regression analysis, both VT2WI and VDWI were positively correlated with NPV, with R2 reaching 0.96 and 0.97, respectively. CONCLUSIONS: Both T2WI and DWI have the potential for efficient evaluation of HIFU treatment in adenomyosis, and DWI can be a replacement for CE-T1WI to some extent.

Evaluation of the timing and safety of hysteroscopic myomectomy of large submucosal fibroids pretreated by high intensity focused ultrasound.

OBJECTIVES: To evaluate the timing and safety of hysteroscopic myomectomy for large submucosal fibroids pretreated with high intensity focused ultrasound (HIFU). MATERIALS AND METHODS: From June 2011 to December 2020, 74 patients with solitary submucousal fibroid with size larger than 4 cm who received HIFU treatment followed by hysteroscopic myomectomy were enrolled. RESULTS: The average age of patients was 40.2 ± 6.7 years. Among them, 1 had type 0, 18 had type I and 55 patients had type II submucosal fibroids. The mean diameter of fibroids was 5.7 ± 1.2 cm. All patients completed HIFU in one session, and the median non-perfused volume (NPV) ratio achieved in fibroids was 90.5%. Hysteroscopic myomectomy was performed in 0-1, 1-3, 3-6, and 6-12 months after HIFU. The mean shrinkage rate of fibroids post-HIFU was 68.19 ± 19.86%, 61.10 ± 16.89%, and 63.76 ± 26.68% in 1-3 months, 3-6 months and 6-12 months, respectively. All patients completed hysteroscopic myomectomy successfully, and no intrauterine adhesion after HIFU was observed. The complete resection of fibroids achieved in 69 patients in one session of the procedure. The mean operation time was 66.66 ± 31.61 min, the median blood loss was 20 ml, and the median distention medium deficit was 275 ml. No significant difference was observed in the operation time, blood loss and distention medium deficit among patients who received hysteroscopic myomectomy at different time points (p > 0.05). CONCLUSIONS: HIFU can be used as a pretreatment for large submucosal fibroids before hysteroscopic myomectomy. Based on our results, hysteroscopic myomectomy could be performed at any time point, even within 1 month after HIFU.

Successful pregnancies in women with diffuse uterine leiomyomatosis after high-intensity focused ultrasound ablation: report of three cases.

OBJECTIVE: To describe the reproductive outcomes of patients with diffuse uterine leiomyomatosis (DUL) treated with high-intensity focused ultrasound (HIFU) ablation. MATERIALS AND METHODS: Three patients of reproductive age with DUL who underwent HIFU treatment were enrolled, all of whom had a strong desire to become pregnant. All patients underwent routine laboratory tests, electrocardiography (ECG), chest X-ray radiography, ultrasound, and magnetic resonance imaging (MRI) examinations after routine medical history collection and physical examination. The treatment time, treatment power, sonication time, and adverse events were recorded. One day after HIFU, MRI was performed to evaluate treatment efficacy. The patients were scheduled for follow-up at 3-, 6-, 12-, and 24-month after HIFU treatment. RESULTS: All the three patients completed HIFU treatment successfully without any major complication. Uterine size and menstrual volume significantly decreased with the combination of medical and HIFU treatments. The shrinkage rate of uterine volume was 31-44% and the menstrual volume reduced by 1/2 or returned to normal at 3 months post-HIFU. Three patients had successful conceptions between 3 and 11 months after HIFU with healthy deliveries. No uterine rupture occurred during pregnancy and delivery. CONCLUSION: HIFU ablation may help achieve a successful pregnancy in patients with DUL.

Comparison of high-intensity focused ultrasound for the treatment of internal and external adenomyosis based on magnetic resonance imaging classification.

OBJECTIVE: To compare the safety and efficacy of high-intensity focused ultrasound (HIFU) treatment for patients with internal or external adenomyosis based on magnetic resonance imaging (MRI) classification. MATERIALS AND METHODS: A total of 238 patients with internal adenomyosis and 167 patients with external adenomyosis who received HIFU treatment were enrolled. HIFU treatment results and adverse effects between patients with internal and external adenomyosis were compared. RESULTS: The treatment time and sonication time for patients with external adenomyosis were significantly longer than that for patients with internal adenomyosis. The total energy used and EEF for patients with external adenomyosis were higher than that for patients with internal adenomyosis (p < 0.05). The pre-HIFU median dysmenorrhea score in patients with internal or external adenomyosis was 5 or 8 points, the median score decreased to 1 or 3 points in these two groups at 18-month post-HIFU (p < 0.05). The relief rate of dysmenorrhea was 79.5% in patients with internal adenomyosis, and it was 80.8% in patients with external adenomyosis. The pre-HIFU median menorrhagia score in patients with internal or external adenomyosis was 4 or 3 points, the median score decreased to 1 point in both groups at 18-month post-HIFU with a relief rate of 86.2% and 77.1%, respectively (p = 0.030). No serious complication occurred in any of these patients. CONCLUSIONS: HIFU is a safe and effective treatment either for patients with internal adenomyosis or external adenomyosis. It seemed that internal adenomyosis is easier to be treated with HIFU and with a higher relief rate of menorrhagia than external adenomyosis.

A point mutation in the gene encoding magnesium chelatase I subunit influences strawberry leaf color and metabolism.

Magnesium chelatase (MgCh) catalyzes the insertion of magnesium into protoporphyrin IX, a vital step in chlorophyll (Chl) biogenesis. The enzyme consists of 3 subunits, MgCh I subunit (CHLI), MgCh D subunit (CHLD), and MgCh H subunit (CHLH). The CHLI subunit is an ATPase that mediates catalysis. Previous studies on CHLI have mainly focused on model plant species, and its functions in other species have not been well described, especially with regard to leaf coloration and metabolism. In this study, we identified and characterized a CHLI mutant in strawberry species Fragaria pentaphylla. The mutant, noted as p240, exhibits yellow-green leaves and a low Chl level. RNA-Seq identified a mutation in the 186th amino acid of the CHLI subunit, a base conserved in most photosynthetic organisms. Transient transformation of wild-type CHLI into p240 leaves complemented the mutant phenotype. Further mutants generated from RNA-interference (RNAi) and CRISPR/Cas9 gene editing recapitulated the mutant phenotype. Notably, heterozygous chli mutants accumulated more Chl under low light conditions compared with high light conditions. Metabolite analysis of null mutants under high light conditions revealed substantial changes in both nitrogen and carbon metabolism. Further analysis indicated that mutation in Glu186 of CHLI does not affect its subcellular localization nor the interaction between CHLI and CHLD. However, intramolecular interactions were impaired, leading to reduced ATPase and MgCh activity. These findings demonstrate that Glu186 plays a key role in enzyme function, affecting leaf coloration via the formation of the hexameric ring itself, and that manipulation of CHLI may be a means to improve strawberry plant fitness and photosynthetic efficiency under low light conditions.

Therapeutic dose and long-term efficacy of high-intensity focused ultrasound ablation for different types of uterine fibroids based on signal intensity on T2-weighted MR images.

OBJECTIVE: To investigate the therapeutic dose and long-term efficacy of high-intensity focused ultrasound (HIFU) ablation for different types of uterine fibroids based on signal intensity on T2-weighted MR images (T2WI). MATERIALS AND METHODS: Four hundred and one patients with a solitary uterine fibroid treated with HIFU were classified into four groups consisting of extremely hypointense, hypointense, isointense and hyperintense fibroids. Each group was further classified into two subtypes: homogeneous and heterogeneous, based on signal homogeneity of fibroids. The therapeutic dose and long-term follow-up results were compared. RESULTS: There were significant differences in treatment time, sonication time, treatment intensity, total treatment dosage, treatment efficiency, energy-efficiency factor (EEF) and non-perfused volume (NPV) ratio among the four groups (p<.05). The average NPV ratio achieved in patients with extremely hypointense, hypointense, isointense and hyperintense fibroids was 75.2 ± 14.6%, 71.1 ± 15.6%, 68.2 ± 17.3% and 67.8 ± 16.6%, respectively; the re-intervention rates at 36 months after HIFU were 8.4%, 10.3%, 12.5% and 6.1%, respectively. Sonication time, treatment intensity and total energy for heterogeneous fibroids were greater than that for homogeneous fibroids in patients with extremely hypointense fibroids (p<.05). The treatment time for heterogeneous fibroids was significantly longer than that for homogeneous fibroids in patients with isointense fibroids (p<.05). Multivariate ordered logistic regression analysis showed that the ablation volume of fibroids and treatment time were related to NPV ratio (p<.05). CONCLUSION: Every group of patients obtained satisfactory long-term results. Hyperintense fibroids are difficult to treat by HIFU. Heterogeneous fibroids are more difficult to treat with HIFU than homogeneity fibroids.

Multitarget-Directed Gallium(III) Tris(acyl-pyrazolonate) Complexes Induce Ferroptosis in Cancer Cells via Dysregulation of Cell Redox Homeostasis and Inhibition of the Mevalonate Pathway.

A series of Ga(Qn)3 coordination compounds have been synthesized, where HQn is 1-phenyl-3-methyl-4-RC(═O)-pyrazolo-5-one. The complexes have been characterized through analytical data, NMR and IR spectroscopy, ESI mass spectrometry, elemental analysis, X-ray crystallography, and density functional theory (DFT) studies. Cytotoxic activity against a panel of human cancer cell lines was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, with interesting results in terms of both cell line selectivity and toxicity values compared with cisplatin. The mechanism of action was explored by spectrophotometric, fluorometric, chromatographic, immunometric, and cytofluorimetric assays, SPR biosensor binding studies, and cell-based experiments. Cell treatment with gallium(III) complexes promoted several cell death triggering signals (accumulation of p27, PCNA, PARP fragments, activation of the caspase cascade, and inhibition of the mevalonate pathway) and induced changes in cell redox homeostasis (decreased levels of GSH/GPX4 and NADP(H), increased reactive oxygen species (ROS) and 4-hydroxynonenal (HNE), mitochondrial damage, and increased activity of CPR and CcO), identifying ferroptosis as the mechanism responsible for cancer cell death.

Targeting Proteolysis with Cyanogenic Glycoside Amygdalin Induces Apoptosis in Breast Cancer Cells.

BACKGROUND: Breast cancer is the most diagnosed cancer among women, and its incidence and mortality are rapidly growing worldwide. In this regard, plant-derived natural compounds have been shown to be effective as chemotherapeutic and preventative agents. Apricot kernels are a rich source of nutrients including proteins, lipids, fibers, and phenolic compounds and contain the aromatic cyanogenic glycoside amygdalin that has been shown to exert a cytotoxic effect on cancer cells by affecting the cell cycle, inducing apoptosis, and regulating the immune function. METHODS: Here, we describe a previously unexplored proapoptotic mechanism of action of amygdalin in breast cancer (MCF7) cells that involves the modulation of intracellular proteolysis. For comparative purposes, the same investigations were also conducted upon cell treatment with two apricot kernel aqueous extracts from Prunus armeniaca L. RESULTS: We observed that both the 20S and 26S proteasome activities were downregulated in the MCF7 cells upon 24 h treatments. Simultaneously, the autophagy cascade resulted in being impaired due to cathepsin B and L inhibition that also contributed to a reduction in cancer cell migration. The inhibition of these proteolytic systems finally promoted the activation of apoptotic events in the MCF7 cells. CONCLUSION: Collectively, our data unveil a novel mechanism of the anticancer activity of amygdalin, prompting further investigations for potential application in cancer preventative strategies.

miR2119, a Novel Transcriptional Regulator, Plays a Positive Role in Woody Plant Drought Tolerance by Mediating the Degradation of the CkBI-1 Gene Associated with Apoptosis.

Caragana korshinskii, an important vegetation restoration species with economic and ecological benefits in the arid region of northwest China, is characterized by significant drought tolerance. However, the underlying molecular mechanisms by which miRNAs confer this trait in C. korshinskii are unclear. Here, we investigate the effect of CkmiR2119 on drought tolerance and identified its target gene, CkBI-1. A negative correlation of CkmiR2119 and CkBI-1 in both stems and leaves in a drought gradient treatment followed by target gene validation suggest that CkmiR2119 might negatively regulate CkBI-1. Consistently, a decrease in the expression of the CkBI-1 gene was observed after both transient transformation and stable transformation of CkamiR2119 in tobacco (Nicotiana tabacum). Moreover, the physiological analysis of CkamiR2119 and CkBI-1 transgenic plants further indicate that CkmiR2119 can enhance the drought tolerance of C. korshinskii in two aspects: (i) downregulating CkBI-1 expression to accelerate vessel maturation in stems; (ii) contributing to a higher level of CkBI-1 in mesophyll cells to inhibit programmed cell death (PCD). This work reveals that CkmiR2119 can increase plants' drought tolerance by downregulating the expression of CkBI-1, providing a theoretical basis to improve plants' ability to withstand stress tolerance by manipulating miRNAs.

Magnetic resonance imaging parameter-based machine learning for prognosis prediction of high-intensity focused ultrasound ablation of uterine fibroids.

Objectives: To develop and apply magnetic resonance imaging (MRI) parameter-based machine learning (ML) models to predict non-perfused volume (NPV) reduction and residual regrowth of uterine fibroids after high-intensity focused ultrasound (HIFU) ablation.Methods: MRI data of 573 uterine fibroids in 410 women who underwent HIFU ablation from the Chongqing Haifu Hospital (training set, N = 405) and the First Affiliated Hospital of Chongqing Medical University (testing set, N = 168) were retrospectively analyzed. Fourteen MRI parameters were screened for important predictors using the Boruta algorithm. Multiple ML models were constructed to predict NPV reduction and residual fibroid regrowth in a median of 203.0 (interquartile range: 122.5-367.5) days. Furthermore, optimal models were used to plot prognostic prediction curves.Results: Fourteen features, including postoperative NPV, indicated predictive ability for NPV reduction. Based on the 10-fold cross-validation, the best average performance of multilayer perceptron achieved with R2 was 0.907. In the testing set, the best model was linear regression (R2 =0.851). Ten features, including the maximum thickness of residual fibroids, revealed predictive power for residual fibroid regrowth. Random forest model achieved the best performance with an average area under the curve (AUC) of 0.904 (95% confidence interval (CI), 0.869-0.939), which was maintained in the testing set with an AUC of 0.891 (95% CI, 0.850-0.929).Conclusions: ML models based on MRI parameters can be used for prognostic prediction of uterine fibroids after HIFU ablation. They can potentially serve as a new method for learning more about ablated fibroids.

Evaluation of high intensity focused ultrasound treatment for different types of adenomyosis based on magnetic resonance imaging classification.

OBJECTIVE: To evaluate the mid-term symptom improvement of patients with different types of adenomyosis based on magnetic resonance imaging (MRI) classification after ultrasound-guided high intensity focused ultrasound (USgHIFU) treatment. MATERIALS AND METHODS: A total of 321 patients with adenomyosis who underwent HIFU and completed 18-month follow-up were retrospectively reviewed. Based on the relationship between the adenomyotic lesion and the uterine structural components on T2-weighted imaging (T2WI), adenomyotic lesions were classified as internal, external, full thickness and intramural adenomyosis. Based on the extent of the myometrial involvement, these lesions were further subclassified as asymmetric and symmetric adenomyosis. RESULTS: All patients completed HIFU ablation in one session. The range of median menstrual pain score in patients with asymmetric internal, symmetric internal, asymmetric external, asymmetric full thickness, symmetric full thickness, and intramural adenomyosis was between 6 and 8 points before HIFU, the median menstrual pain score decreased to 2-4 points 18-month post-HIFU (p < .005). The menstrual pain relief rate was 68.3%, 62.1%, 54.7%, 64.1%, 60%, and 100%, respectively. The median menstrual blood volume score range was between 2 and 4 points in the different groups of patients before HIFU, it decreased to 1-3 points 18-month after HIFU with a relief rate of 68.3%, 51.6%, 51.0%, 55.5%, 57.2%, and 100%, respectively. No serious complication occurred in any of these patients. CONCLUSIONS: Based on our results, USgHIFU is safe and effective in the treatment of patients with different subtypes of adenomyosis with mid-term sustained improvement in symptoms of menstrual pain and menstrual blood volume.

Overexpression of γ-glutamylcysteine synthetase gene from Caragana korshinskii decreases stomatal density and enhances drought tolerance.

BACKGROUND: Gamma-glutamylcysteine synthetase (γ-ECS) is a rate-limiting enzyme in glutathione biosynthesis and plays a key role in plant stress responses. In this study, the endogenous expression of the Caragana korshinskii γ-ECS (Ckγ-ECS) gene was induced by PEG 6000-mediated drought stress in the leaves of C. korshinskii. and the Ckγ-ECS overexpressing transgenic Arabidopsis thaliana plants was constructed using the C. korshinskii. isolated γ-ECS. RESULTS: Compared with the wildtype, the Ckγ-ECS overexpressing plants enhanced the γ-ECS activity, reduced the stomatal density and aperture sizes; they also had higher relative water content, lower water loss, and lower malondialdehyde content. At the same time, the mRNA expression of stomatal development-related gene EPF1 was increased and FAMA and STOMAGEN were decreased. Besides, the expression of auxin-relative signaling genes AXR3 and ARF5 were upregulated. CONCLUSIONS: These changes suggest that transgenic Arabidopsis improved drought tolerance, and Ckγ-ECS may act as a negative regulator in stomatal development by regulating the mRNA expression of EPF1 and STOMAGEN through auxin signaling.

Ultrasound-guided high intensity focused ultrasound ablation for uterine fibroids: long-term outcomes and factors affecting local recurrence.

OBJECTIVE: To assess the long-term outcomes and the factors affecting local recurrence of uterine fibroids after ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation. MATERIALS AND METHODS: 629 patients with a solitary uterine fibroid smaller than 10 cm in diameter treated with USgHIFU at our institutes between January 2011 and December 2016 were retrospectively analyzed. The patients were requested to take pre-HIFU and one day post-HIFU MRI. The patients were asked to return to the hospital every 3 months until January 2020, for imaging evaluation and to check on improvement in symptoms. RESULTS: Five hundred and thirty-six patients completed follow-up according to our protocol. The median follow-up time was 69 (interquartile range: 48 to 89) months. Among them, local recurrence was detected in 110 patients. 18 (16.4%) patients required additional treatment between 12 and 24 months after USgHIFU treatment, 59 (53.6%) patients required additional treatment 24 months after USgHIFU. Therefore, in total, 77 patients required additional treatment, of which 32 received USgHIFU and 45 underwent myomectomy. The median non-perfused volume (NPV) ratio in patients with recurrence was 73%, compared to 89% among patients without recurrence. Multivariate analysis showed that NPV ratio, maximum fibroid diameter and fibroid enhancement type were the independent factors affecting the recurrence of fibroids after USgHIFU treatment. CONCLUSIONS: Achievement of NPV ratio higher than 70% has led to acceptable re-intervention rate during the follow-up period after USgHIFU. NPV ratio, maximum fibroid diameter, and fibroid enhancement type were the independent factors affecting the recurrence of fibroids after USgHIFU treatment.

MRI features and clinical outcomes of unexpected uterine sarcomas in patients who underwent high-intensity focused ultrasound ablation for presumed uterine fibroids.

OBJECTIVE: To investigate the MRI features and clinical outcomes of unexpected uterine sarcomas in patients after high-intensity focused ultrasound (HIFU) ablation for presumed uterine fibroids. MATERIALS AND METHODS: 15,759 consecutive patients who came for HIFU treatment, from November 2008 to September 2019, for presumed uterine fibroids were retrospectively reviewed. All the patients had completed a pre-HIFU MRI. All MRI images were independently analyzed and interpreted by two radiologists in every center. RESULTS: According to the T2WI MRI features of hyperintensity, accompanied by irregular margins, necrosis or cystic degeneration, multi-lobulated lesion with internal septation, 46 patients were suspected to be uterine sarcomas before HIFU. Eleven patients were histologically diagnosed as uterine sarcomas after laparotomy. Among the 15713 patients who received HIFU treatment for presumed uterine fibroids, 8 patients were found to have occult recurrence during the follow-up period, and 6 were confirmed histologically as uterine sarcomas after laparotomy. The incidence rate of uterine sarcomas was 0.108% (17/15759). Among them, 12 cases were low-grade endometrial stromal sarcoma (LG-ESS) and 5 cases were uterine leiomyosarcoma (LMS). No histological dissemination of the sarcoma was detected in patients with unexpected uterine sarcomas. CONCLUSION: Although some MRI features of uterine sarcomas and uterine fibroids overlapped, MRI is valuable in distinguishing between uterine fibroids and uterine sarcomas. HIFU does not seem to cause histological dissemination of the sarcoma, but follow-up visits should be strictly adhered to in order to detect unexpected uterine sarcomas at an early stage and to treat them in a timely manner.

Flavan-3-ol Microbial Metabolites Modulate Proteolysis in Neuronal Cells Reducing Amyloid-beta (1-42) Levels.

INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegeneration characterized by extensive protein aggregation and deposition in the brain, associated with defective proteasomal and autophagic-lysosomal proteolytic pathways. Since current drugs can only reduce specific symptoms, the identification of novel treatments is a major concern in AD research. Among natural compounds, (poly)phenols and their derivatives/metabolites are emerging as candidates in AD prevention due to their multiple beneficial effects. This study aims to investigate the ability of a selection of phenyl-γ-valerolactones, gut microbiota-derived metabolites of flavan-3-ols, to modulate the functionality of cellular proteolytic pathways. METHODS AND RESULTS: Neuronal SH-SY5Y cells transfected with either the wild-type or the 717 valine-to-glycine amyloid precursor protein mutated gene are used as an AD model and treated with 5-(4'-hydroxyphenyl)-γ-valerolactone, 5-(3',4'-dihydroxyphenyl)-γ-valerolactone and 5-(3'-hydroxyphenyl)-γ-valerolactone-4'-sulfate. Combining in vitro and in silico studies, it is observed that the phenyl-γ-valerolactones of interest modulated cellular proteolysis via proteasome inhibition and consequent autophagy upregulation and inhibited cathepsin B activity, eventually reducing the amount of intra- and extracellular amyloid-beta (1-42) peptides. CONCLUSION: The findings of this study establish, for the first time, that these metabolites exert a neuroprotective activity by regulating intracellular proteolysis and confirm the role of autophagy and cathepsin B as possible targets of AD preventive/therapeutic strategies.

Association between CASC16 rs4784227 polymorphism and breast cancer susceptibility: A meta-analysis.

OBJECTIVE: To explore whether rs4784227 polymorphism of CASC16 is correlated with risk of breast cancer. METHODS: Relevant studies up to December 24, 2020 were searched in PubMed, Embase, Web of Science, CNKI, VIP, and WANFANG databases. Data were analyzed by using Stata 12.0. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and country-based subgroup analyses were conducted. Sensitivity analysis was conducted to assess the stability of the results. Publication bias was assessed by using the Egger regression asymmetry test and visualization of funnel plots. RESULTS: Seven case-control studies enrolling 4055 breast cancer cases and 4229 controls were included. rs4784227 was found significantly associated with increased risk of breast cancer in a dominant (OR = 1.301, 95% CI = 1.190-1.423, P < .001), a recessive (OR = 1.431, 95% CI = 1.216-1.685, P < .001), and an allele model (OR = 1.257, 95% CI = 1.172-1.348, P < .001), while an over-dominant model showed that rs4784227 was correlated with decreased breast cancer risk (OR = 0.852, 95% CI = 0.778-0.933, P = .001). CONCLUSION: The rs4784227 polymorphism of CASC16 gene is correlated with breast cancer susceptibility.

A comparison of results following the treatment of placenta accreta and placenta increta using high-intensity focused ultrasound followed by hysteroscopic resection.

OBJECTIVE: To compare the safety and efficacy of high-intensity focused ultrasound (HIFU) followed by hysteroscopic resection for different placenta accreta spectrum disorders. MATERIALS AND METHODS: Thirty-four patients with placenta accreta, placenta increta, or placenta percreta were treated with USgHIFU from January 2016 to December 2019 and were retrospectively reviewed. The patients were classified into three categories according to the relationship between the trophoblastic villi and the myometrium, based on magnetic resonance imaging (MRI). Fifteen patients were classified as placenta accreta, 17 patients were classified as placenta increta, and 2 were classified as placenta percreta. All patients completed follow-up. Treatment efficacy and safety were evaluated. RESULTS: No significant differences in baseline characteristics and results of HIFU ablation were observed between the patients with placenta accreta and those with placenta increta. The return of HCG levels to normal was longer in patients with placenta accreta compared with patients with placenta increta, while no significant difference was observed in the amount of intraoperative blood loss, the return of normal menstruation and the length of hospital stay. CONCLUSIONS: HIFU treatment followed by hysteroscopic resection is safe and effective in the treatment of patients with placenta accreta and placenta increta.