miniSNV: accurate and fast single nucleotide variant calling from nanopore sequencing data.

Nanopore sequence technology has demonstrated a longer read length and enabled to potentially address the limitations of short-read sequencing including long-range haplotype phasing and accurate variant calling. However, there is still room for improvement in terms of the performance of single nucleotide variant (SNV) identification and computing resource usage for the state-of-the-art approaches. In this work, we introduce miniSNV, a lightweight SNV calling algorithm that simultaneously achieves high performance and yield. miniSNV utilizes known common variants in populations as variation backgrounds and leverages read pileup, read-based phasing, and consensus generation to identify and genotype SNVs for Oxford Nanopore Technologies (ONT) long reads. Benchmarks on real and simulated ONT data under various error profiles demonstrate that miniSNV has superior sensitivity and comparable accuracy on SNV detection and runs faster with outstanding scalability and lower memory than most state-of-the-art variant callers. miniSNV is available from https://github.com/CuiMiao-HIT/miniSNV.

Kled: an ultra-fast and sensitive structural variant detection tool for long-read sequencing data.

Structural Variants (SVs) are a crucial type of genetic variant that can significantly impact phenotypes. Therefore, the identification of SVs is an essential part of modern genomic analysis. In this article, we present kled, an ultra-fast and sensitive SV caller for long-read sequencing data given the specially designed approach with a novel signature-merging algorithm, custom refinement strategies and a high-performance program structure. The evaluation results demonstrate that kled can achieve optimal SV calling compared to several state-of-the-art methods on simulated and real long-read data for different platforms and sequencing depths. Furthermore, kled excels at rapid SV calling and can efficiently utilize multiple Central Processing Unit (CPU) cores while maintaining low memory usage. The source code for kled can be obtained from https://github.com/CoREse/kled.

MEHunter: transformer-based mobile element variant detection from long reads.

SUMMARY: Mobile genetic elements (MEs) are heritable mutagens that significantly contribute to genetic diseases. The advent of long-read sequencing technologies, capable of resolving large DNA fragments, offers promising prospects for the comprehensive detection of ME variants (MEVs). However, achieving high precision while maintaining recall performance remains challenging mainly brought by the variable length and similar content of MEV signatures, which are often obscured by the noise in long reads. Here, we propose MEHunter, a high-performance MEV detection approach utilizing a fine-tuned transformer model adept at identifying potential MEVs with fragmented features. Benchmark experiments on both simulated and real datasets demonstrate that MEHunter consistently achieves higher accuracy and sensitivity than the state-of-the-art tools. Furthermore, it is capable of detecting novel potentially individual-specific MEVs that have been overlooked in published population projects. AVAILABILITY AND IMPLEMENTATION: MEHunter is available from https://github.com/120L021101/MEHunter.

Role of interdependent self-construal in predicting acute salivary cortisol response, hair cortisol concentrations, and their associations.

Numerous studies have associated interdependent self-construal (InterSC) with heightened acute salivary cortisol stress responses in collectivist cultures. Hair cortisol concentration (HCC) is an important biomarker of chronic stress and is associated with acute salivary cortisol stress response. However, few studies have explored the association between InterSC and HCC. This study aimed to investigate the role of InterSC in the acute salivary cortisol stress response, HCC, and their associations. Seventy-seven healthy Chinese participants underwent assessments of InterSC, social anxiety, and HCC. The ScanSTRESS paradigm was used to induce an acute stress response and saliva samples were collected. These results replicated earlier findings showing that InterSC was associated with rapid salivary cortisol reactivity and recovery during acute stress. Additionally, InterSC was positively correlated with HCC, and social anxiety mediated this association. Importantly, InterSC moderated the HCC-acute salivary cortisol stress response association. Specifically, high HCC predicted a blunted acute salivary cortisol stress response in participants with low InterSC, including a slow salivary cortisol response during the acute stress reactivity phase and a small overall acute salivary cortisol response. However, this blunting effect was not observed with high InterSC participants, indicating that high InterSC buffered the blunting effect of HCC on the acute salivary cortisol stress response. In conclusion, this study provided new insights into how InterSC is associated with the hypothalamus-pituitary-adrenal axis stress system and revealed the dual-faceted role of InterSC for acute salivary cortisol stress and HCC.

Hyperbranched Polymeric 19F MRI Contrast Agents with Long T2 Relaxation Time Based on ß-Cyclodextrin and Phosphorycholine.

19F magnetic resonance imaging (19F MRI) is gaining attention as an emerging diagnostic technology. Effective 19F MRI contrast agents (CAs) for in vivo applications require a long transverse (or spin-spin) relaxation time (T2), short longitudinal (or spin-lattice) relaxation time (T1), high fluorine content, and excellent biocompatibility. Here, we present a novel hyperbranched polymeric 19F MRI CA based on ß-cyclodextrin and phosphorylcholine. The influence of the branching degree and fluorine content on T2 was thoroughly investigated. Results demonstrated a maximum fluorine content of 11.85% and a T2 of 612 ms. This hyperbranched polymeric 19F MRI CA exhibited both great biocompatibility against cells and organs of mice and high-performance imaging capabilities both in vitro and in vivo. The research provides positive insights into the synthesis strategies, topological design, and selection of fluorine tags for 19F MRI CAs.

Quantitative label-free proteomic analysis of excretory-secretory proteins in different developmental stages of Trichinella spiralis.

Trichinella spiralis (T. spiralis) is a zoonotic parasitic nematode with a unique life cycle, as all developmental stages are contained within a single host. Excretory-secretory (ES) proteins are the main targets of the interactions between T. spiralis and the host at different stages of development and are essential for parasite survival. However, the ES protein profiles of T. spiralis at different developmental stages have not been characterized. The proteomes of ES proteins from different developmental stages, namely, muscle larvae (ML), intestinal infective larvae (IIL), preadult (PA) 6 h, PA 30 h, adult (Ad) 3 days post-infection (dpi) and Ad 6 dpi, were characterized via label-free mass spectrometry analysis in combination with bioinformatics. A total of 1217 proteins were identified from 9341 unique peptides in all developmental stages, 590 of which were quantified and differentially expressed. GO classification and KEGG pathway analysis revealed that these proteins were important for the growth of the larvae and involved in energy metabolism. Moreover, the heat shock cognate 71 kDa protein was the centre of protein interactions at different developmental stages. The results of this study provide comprehensive proteomic data on ES proteins and reveal that these ES proteins were differentially expressed at different developmental stages. Differential proteins are associated with parasite survival and the host immune response and may be potential early diagnostic antigen or antiparasitic vaccine candidates.

QTc prolongation after aneurysmal subarachnoid hemorrhage might be associated with worse neurologic outcome in patients receiving microsurgical clipping or embolization of the intracranial aneurysms: a retrospective observational study.

PURPOSE: QT interval prolongation is one of the most common electrocardiographic (ECG) abnormalities in patients with aneurysmal subarachnoid hemorrhage (aSAH). Whether corrected QT interval (QTc) prolongation is associated with perioperative cardiac events and dismal neurological outcome in mid to long-term follow-up in patients after aSAH is insufficiently studied and remains controversial. METHODS: We retrospectively studied the adult (≥ 18 years) patients admitted to our institution between Jan 2018 and Dec 2020 for aSAH who underwent intracranial aneurysm clipping or embolization. The patients were divided into 2 groups (normal and QTc prolongation groups) according to their QTc. To minimize the confounding bias, a propensity score matching (PSM) analysis was performed to compare the neurologic outcomes between patients with normal QTc and QTc prolongation. RESULTS: After screening, 908 patients were finally included. The patients were divided into 2 groups: normal QTc groups (n = 714) and long QTc group (n = 194). Female sex, hypokalemia, posterior circulation aneurysm, and higher Hunt-Hess grade were associated with QTc prolongation. In multiple regression analysis, older age, higher hemoglobin level, posterior circulation aneurysm, and higher Hunt-Hess grade were identified to be associated with worse outcome during 1-year follow-up. Before PSM, patients with QTc prolongation had higher rate of perioperative cardiac arrest or ventricular arrhythmias. After PSM, there was no statistical difference between normal and QTc prolongation groups in perioperative cardiac events. However, patients in the QTc prolongation group still had worse neurologic outcome during 1-year follow-up. CONCLUSIONS: QTc prolongation is associated with worse outcome in patients following SAH, which is independent of perioperative cardiac events.

Construction of BaTiO3-TiO2 hollow sphere heterojunctions for enhanced microwave dynamic therapy in cancer treatment.

Cancer is one of the primary health concerns among humans due to its high incidence rate and lack of effective treatment. Currently, medical techniques to achieve the precise elimination of local cancer lesions with negligible damage to normal tissues are still intensely desired. Herein, we synthesized BaTiO3-TiO2 hollow spheres (BTHSs) for use in microwave dynamic therapy (MWDT) for cancer. Under UV irradiation, BTHSs can mediate the production of multiple reactive oxygen species (ROS), mainly 1O2, which results in a rapid photocatalytic degradation rate (97%), 1.6-fold that of commercial P25. Importantly, the ROS production process can be triggered by microwaves to effectively execute MWDT for cancer. Under microwave irradiation, BTHSs exhibit a remarkable therapeutic effect and slight cytotoxicity. In terms of mechanism, the enhanced ROS production efficiency of BTHSs can be attributed to their unique hollow structure and the formation of a type-II heterojunction by the incorporation of BaTiO3. The hollow structure increases the availability of active sites and enhances light scattering, while the BaTiO3-TiO2 heterojunction enhances the photocatalytic activity of TiO2 through charge transfer and electron-hole separation. Overall, this study provides important insights into the design and optimization of sensitizers for MWDT applications.

Positive association between serum bilirubin within the physiological range and serum testosterone levels.

BACKGROUNDS: Research has demonstrated that elevated serum total bilirubin (STB) levels have a beneficial impact on various diseases, particularly metabolic syndrome. This study aims to investigate the association between STB levels and serum testosterone (STT) in order to determine if bilirubin plays a protective role in relation to testosterone deficiency (TD) risk. METHODS: In this study, a total of 6,526 eligible male participants aged 20 years or older were analyzed, all of whom took part in the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2016. To investigate the relationship between STB and STT levels, we employed weighted multivariate regression models along with restricted cubic splines (RCS). Additionally, a subgroup analysis was conducted to explore the heterogeneity of this relationship across different subpopulations. RESULTS: Among the participants, 1,832 individuals (28.07%) were identified as having testosterone deficiency (TD), defined as an STT level below 300 ng/dL. A significant positive correlation between STB and STT levels was observed in both crude and adjusted models (all P < 0.0001). The association between STB and STT levels was found to be statistically significant up to a threshold of 17.1 µmol/L, after which it became statistically insignificant(P for non-linearity = 0.0035). Weighted logistic regression analysis indicated that a 1 µmol/L increase in STB was associated with a 4% decrease in the likelihood of TD (odds ratio = 0.96, P < 0.0001). Subgroup analysis showed that the inverse relationship was limited to individuals aged 60 and over, non-smokers/drinkers, and obese individuals. CONCLUSION: STB within the physiological range(17.1 µmol/L) was positively associated with STT in adult males. The potential protective role of bilirubin regarding testosterone levels merits further exploration.

Analysis of adjacent vertebral fracture after percutaneous vertebroplasty: do radiological or surgical features matter?

PURPOSE: To report the incidence and risk factors of adjacent vertebral fracture (AVF) after percutaneous vertebroplasty (PVP) in patients with osteoporotic vertebral compression fractures (OVCFs). We focused to investigate effect of radiological or surgical features on AVF. METHODS: All patients with OVCFs who were treated with PVP between January 2016 and December 2019 were retrospectively reviewed. Patients were followed up at least 12 months after procedure according to treatment protocol. AVF was defined as postoperatively recurrent intractable back pain and subsequently presence of fracture on magnetic resonance imaging (MRI) in adjacent levels. Clinical, radiological, and surgical factors potentially affecting occurrence of AVF were recorded and analyzed using univariate and multivariate analysis. RESULTS: Totally, 1077 patients with 1077 fractured vertebrae who underwent PVP were enrolled in the study, after inclusion and exclusion criteria were met. Mean follow-up time was 24.3 ± 11.9 months (range, 12-59 months). AVF was identified in 98 (9.1%) patients. Univariate analysis showed that seven significant factors related to AVF were older age, non-traumatic fracture, cortical disruption on anterior wall, cortical disruption on lateral wall, basivertebral foramen, type-B leakage and type-C leakage. In multivariate analysis, two clinical factors, older age (P = 0.031) and non-traumatic fracture (P = 0.002), were significantly associated with AVF. However, any radiological or surgical factor did not reach significance in final model analysis. CONCLUSIONS: Incidence of AVF after PVP in patients with OVCFs was 9.1% (98/1077). Older age and non-traumatic fracture were two clinical risk factors for AVF. Neither radiological nor surgical feature was significantly correlated with AVF.

Whole-genome resequencing reveals new mutations in candidate genes for Beichuan-white goat prolificacya.

In this study, we evaluated the copy number variation in the genomes of two groups of Beichuan-white goat populations with large differences in litter size by FST method, and identified 1739 genes and 485 missense mutations in the genes subject to positive selection. Through functional enrichment, ITGAV, LRP4, CDH23, TPRN, RYR2 and CELSR1 genes, involved in embryonic morphogenesis, were essential for litter size trait, which received intensive attention. In addition, some mutation sites of these genes have been proposed (ITGAV: c.38C > T; TPRN: c.133A > T, c.1192A > G, c.1250A > C; CELSR1: c.7640T > C), whose allele frequencies were significantly changed in the high fecundity goat group. Besides, we found that new mutations at these sites altered the hydrophilicity and 3D structure of the protein. Candidate genes related to litter size in this study and their missense mutation sites were identified. These candidate genes are helpful to understand the genetic mechanism of fecundity in Beichuan white goat, and have important significance for future goat breeding.

Adaptive physiological and metabolic alterations in Staphylococcus aureus evolution under vancomycin exposure.

Staphylococcus aureus can develop antibiotic resistance and evade immune responses, causing infections in different body sites. However, the metabolic changes underlying this process are poorly understood. A variant strain, C1V, was derived from the parental strain C1 by exposing it to increasing concentrations of vancomycin in vitro. C1V exhibited a vancomycin-intermediate phenotype and physiological changes compared to C1. It showed higher survival rates than C1 when phagocytosed by Raw264.7 cells. Metabolomics analysis identified significant metabolic differences pre- and post-induction (C1 + SC1 vs. C1V + SC1V: 201 metabolites) as well as pre- and post-phagocytosis (C1 vs. SC1: 50 metabolites; C1V vs. SC1V: 95 metabolites). The variant strain had distinct morphological characteristics, decreased adhesion ability, impaired virulence, and enhanced resistance to phagocytosis compared to the parental strain. Differential metabolites may contribute to S. aureus ' resistance to antibiotics and phagocytosis, offering insights into potential strategies for altering vancomycin nonsusceptibility and enhancing phagocyte killing by manipulating bacterial metabolism.

Facet Engineering and Pore Design Boost Dynamic Fe Exchange in Oxygen Evolution Catalysis to Break the Activity-Stability Trade-Off.

The oxygen evolution reaction (OER) plays a vital role in renewable energy technologies, including in fuel cells, metal-air batteries, and water splitting; however, the currently available catalysts still suffer from unsatisfactory performance due to the sluggish OER kinetics. Herein, we developed a new catalyst with high efficiency in which the dynamic exchange mechanism of active Fe sites in the OER was regulated by crystal plane engineering and pore structure design. High-density nanoholes were created on cobalt hydroxide as the catalyst host, and then Fe species were filled inside the nanoholes. During the OER, the dynamic Fe was selectively and strongly adsorbed by the (101̅0) sites on the nanohole walls rather than the (0001) basal plane, and at the same time the space-confining effect of the nanohole slowed down the Fe diffusion from catalyst to electrolyte. As a result, a local high-flux Fe dynamic equilibrium inside the nanoholes for OER was achieved, as demonstrated by the Fe57 isotope labeled mass spectrometry, thereby delivering a high OER activity. The catalyst showed a remarkably low overpotential of 228 mV at a current density of 10 mA cm-2, which is among the best cobalt-based catalysts reported so far. This special protection strategy for Fe also greatly improved the catalytic stability, reducing the Fe leaching amount by 2 orders of magnitude compared with the pure Fe hydroxide catalyst and thus delivering a long-term stability of 130 h. An assembled Zn-air battery was stably cycled for 170 h with a low discharge/charge voltage difference of 0.72 V.

Reversible Iron Oxyfluoride (FeOF)-Graphene Composites as Sustainable Cathodes for High Energy Density Lithium Batteries.

Two large barriers are impeding the wide implementation of electric vehicles, namely driving-range and cost, primarily due to the low specific energy and high cost of mono-valence cathodes used in lithium-ion batteries. Iron is the ideal element for cathode materials considering its abundance, low cost and toxicity. However, the poor reversibility of (de)lithiation and low electronic conductivity prevent iron-based high specific energy multi-valence conversion cathodes from practical applications. In this work, a sustainable FeOF nanocomposite is developed with extraordinary performance. The specific capacity and energy reach 621 mAh g-1 and 1124 Wh kg-1 with more than 100 cycles, which triples the specific capacity, and doubles the specific energy of current mono-valence intercalation LiCoO2 . This is the result of an effective approach, combing the nanostructured FeOF with graphene, realized by making the (de)lithiation reversible by immobilizing FeOF nanoparticles and the discharge products over the graphene surface and providing the interparticle electric conduction. Importantly, it demonstrates that introducing small amount of graphene can create new materials with desired properties, opening a new avenue for altering the (de)lithiation process. Such extraordinary performance represents a significant breakthrough in developing sustainable conversion materials, eventually overcoming the driving range and cost barriers.

Biomedical Application of Porphyrin-Based Amphiphiles and Their Self-Assembled Nanomaterials.

Porphyrins have been vastly explored and applied in many cutting-edge fields with plenty of encouraging achievements because of their excellent properties. As important derivatives of porphyrins, porphyrin-based amphiphiles (PBAs) not only maintain the advanced properties of porphyrins (catalysis, imaging, and energy transfer) but also possess self-assembly and encapsulation capability in aqueous solution. Accordingly, PBAs and their self-assembles have had important roles in diagnosing and treating tumors and inflammation lesions in vivo, but not limited to these. In this article, we introduce the research progress of PBAs, including their constitution, structure design strategies, and performances in tumor and inflammation lesion diagnosis and treatments. On that basis, the defects of synthesized PBAs during their application and the possible effective strategies to overcome the limitations are also proposed. Finally, perspectives on PBAs exploration are updated based on our knowledge. We hope this review will bring researchers from various domains insights about PBAs.

Neural habituation during acute stress signals a blunted endocrine response and poor resilience.

BACKGROUND: A blunted hypothalamic-pituitary-adrenal (HPA) axis response to acute stress is associated with psychiatric symptoms. Although the prefrontal cortex and limbic areas are important regulators of the HPA axis, whether the neural habituation of these regions during stress signals both blunted HPA axis responses and psychiatric symptoms remains unclear. In this study, neural habituation during acute stress and its associations with the stress cortisol response, resilience, and depression were evaluated. METHODS: Seventy-seven participants (17-22 years old, 37 women) were recruited for a ScanSTRESS brain imaging study, and the activation changes between the first and last stress blocks were used as the neural habituation index. Meanwhile, participants' salivary cortisol during test was collected. Individual-level resilience and depression were measured using questionnaires. Correlation and moderation analyses were conducted to investigate the association between neural habituation and endocrine data and mental symptoms. Validated analyses were conducted using a Montreal Image Stress Test dataset in another independent sample (48 participants; 17-22 years old, 24 women). RESULTS: Neural habituation of the prefrontal cortex and limbic area was negatively correlated with cortisol responses in both datasets. In the ScanSTRESS paradigm, neural habituation was both positively correlated with depression and negatively correlated with resilience. Moreover, resilience moderated the relationship between neural habituation in the ventromedial prefrontal cortex and cortisol response. CONCLUSIONS: This study suggested that neural habituation of the prefrontal cortex and limbic area could reflect motivation dysregulation during repeated failures and negative feedback, which might further lead to maladaptive mental states.

Exosomal miR-93-5p from cancer-associated fibroblasts confers malignant phenotypes on bladder cancer cells by targeting PAFAH1B1.

BACKGROUND: Dysregulation of cancer-associated fibroblasts (CAFs) still greatly challenges the treatments for bladder cancer (BC), where exosomal miRNAs derived from CAFs are one of the essential effectors for tumor progression. miR-93-5p is reported to be upregulated in BC, however, it is barely investigated in BC-derived CAFs. METHOD: The CAF markers were immunofluorescent-labeled and examined by western blotting assay in CAFs and normal fibroblasts (NFs). CAFs- and NFs-derived exosomes (CAFs-exo/NFs-exo) were authenticated by transmission electron microscope and nanoparticle tracking analysis. Cell viability was determined by cell counting kit-8 assay, and cell mobility was evaluated by wound healing and transwell assays. Real-time quantitative PCR was used to quantify the RNA expressions, and a western blotting assay was used for protein expression. Interaction between miR-93-5p and Platelet-Activating Factor Acetylhydrolase IB Subunit Beta (PAFAH1B1) was verified by luciferase reporter assay. HE staining assay was applied to assess the histological changes of xenografts. RESULTS: CAFs-exo notably enhanced cell mobility and the expression levels of miR-93-5p of BC cells compared to NFs-exo. However, inhibition of miR-93-5p in CAFs-exo exhibited attenuated pro-metastatic ability on BC cells. PAFAH1B1 was one of the predicted targets of miR-93-5p, whose mRNA level was most significantly downregulated after miR-93-5p transfection. The interaction between PAFAH1B1 and miR-93-5p was verified, and miR-93-5p negatively regulated the protein level of PAFAH1B1. Overexpression of PAFAH1B1 could efficiently reverse the effects of miR-93-5p mimic on BC cell mobility. Finally, inhibition of miR-93-5p was proved to impair the carcinogenic function of CAFs-exo in vivo . CONCLUSION: Exosomal miR-93-5p derived from CAFs confers oncogenicity on BC cells via sponging PAFAH1B1, suggesting a novel therapeutic strategy for BC.

EEG-based emergency braking intention detection during simulated driving.

BACKGROUND: Current research related to electroencephalogram (EEG)-based driver's emergency braking intention detection focuses on recognizing emergency braking from normal driving, with little attention to differentiating emergency braking from normal braking. Moreover, the classification algorithms used are mainly traditional machine learning methods, and the inputs to the algorithms are manually extracted features. METHODS: To this end, a novel EEG-based driver's emergency braking intention detection strategy is proposed in this paper. The experiment was conducted on a simulated driving platform with three different scenarios: normal driving, normal braking and emergency braking. We compared and analyzed the EEG feature maps of the two braking modes, and explored the use of traditional methods, Riemannian geometry-based methods, and deep learning-based methods to predict the emergency braking intention, all using the raw EEG signals rather than manually extracted features as input. RESULTS: We recruited 10 subjects for the experiment and used the area under the receiver operating characteristic curve (AUC) and F1 score as evaluation metrics. The results showed that both the Riemannian geometry-based method and the deep learning-based method outperform the traditional method. At 200 ms before the start of real braking, the AUC and F1 score of the deep learning-based EEGNet algorithm were 0.94 and 0.65 for emergency braking vs. normal driving, and 0.91 and 0.85 for emergency braking vs. normal braking, respectively. The EEG feature maps also showed a significant difference between emergency braking and normal braking. Overall, based on EEG signals, it was feasible to detect emergency braking from normal driving and normal braking. CONCLUSIONS: The study provides a user-centered framework for human-vehicle co-driving. If the driver's intention to brake in an emergency can be accurately identified, the vehicle's automatic braking system can be activated hundreds of milliseconds earlier than the driver's real braking action, potentially avoiding some serious collisions.

Exosomal miR-105-5p derived from bladder cancer stem cells targets for GPR12 to promote the malignancy of bladder cancer.

Bladder cancer stem cells (BCSCs) are considered as the root cause of BC initiation and recurrence, and exosomes derived from BCSCs (CSCs-exo) are the vital tool for establishing a stable tumor microenvironment. miR-105-5p has been revealed to promote tumor growth in a variety of cancers, but the effects on BC are still not included.Characteristics of CSCs-exo were examined by transmission electron microscope and nanoparticle tracking analysis. PKH67 dye was used to observe the cellular uptake of exosomes. Cell viability, migration and invasion were detected by CCK-8, wound healing and transwell invasion assays, respectively. The interaction between miR-105-5p and GPR12 was verified by luciferase activity assay. Xenografts were induced in the nude mice, and H&E staining method was applied to analyze the histological changes of xenografts. CSCs-exo efficiently promoted BC cell viability, migration and invasion. miR-105-5p was highly expressed in CSCs and CSCs-exo treatment significantly upregulated the expression of miR-105-5p in BC cells.GPR12 was subsequently verified to be the target gene of miR-105-5p, and overexpression of GPR12 abrogated the effects of miR-105-5p on BC cell growth and metastasis. Reversely, the anti-tumor function of miR-105-5p antagomir was observed in the xenograft mice.CSCs aggravated the malignancy of BC partly through transmitting exosomal miR-105-5p to BC cells to inhibit the expression of GPR12, which developed a novel aspect for CSC-targeted therapies.

Perineal ultrasound to assess the urethral spatial movement in stress urinary incontinence in women.

BACKGROUND: Perineal ultrasound as a non-invasive method for the diagnosis of female stress urinary incontinence has attracted more and more attention. However, the criteria for stress urinary incontinence in women using perineal ultrasound have not been fully established. Our study aimed to evaluate characteristics of the urethral spatial movement with perineal ultrasonography. METHODS: A total of 136 female patients with stress urinary incontinence and 44 controls were enrolled. Stress urinary incontinence was diagnosed using the International Consultation on Incontinence Questionnaire Short Form, medical history and physical examination, and severity was assessed using a 1 h pad test. We described the mobility of four equidistant points (A-D) located along the urethra length. The retrovesical and urethral rotation angles were measured using perineal ultrasonography at rest and during the maximal Valsalva maneuver. RESULTS: Patients with stress urinary incontinence showed a more significant vertical movement at Points A, B and C than controls. The mean variations in the retrovesical angle were significantly larger in patients with stress urinary incontinence at rest and during the Valsalva maneuver than in controls (21.0 ± 16.5° vs. 14.7 ± 20.1°, respectively). The cut-off value for the retrovesical angle variation was 10.7° with 72% sensitivity and 54% specificity. There was a receiver-operating characteristic curve area of 0.73 and 0.72 for Points A and B, respectively. A cut-off of 10.8 mm, and 9.4 mm provided 71% sensitivity and 68% specificity and 67% sensitivity and 75% specificity, respectively. CONCLUSIONS: The spatial movement of the bladder neck and proximal urethra, and variations in the retrovesical angle may be correlated with clinical symptoms and facilitate to the assessment of SUI.