Updated review on analysis of long non-coding RNAs as emerging diagnostic and therapeutic targets in prostate cancers.

Despite advancements, prostate cancers (PCa) pose a significant global health challenge due to delayed diagnosis and therapeutic resistance. This review delves into the complex landscape of prostate cancer, with a focus on long-noncoding RNAs (lncRNAs). Also explores the influence of aberrant lncRNAs expression in progressive PCa stages, impacting traits like proliferation, invasion, metastasis and therapeutic resistance. The study elucidates how lncRNAs modulate crucial molecular effectors, including transcription factors and microRNAs, affecting signaling pathways such as androgen receptor signaling. Besides, this manuscript sheds light on novel concepts and mechanisms driving PCa progression through lncRNAs, providing a critical analysis of their impact on the disease's diverse characteristics. Besides, it discusses the potential of lncRNAs as diagnostics and therapeutic targets in PCa. Collectively, this work highlights state of art mechanistic comprehension and rigorous scientific approaches to advance our understanding of PCa and depict innovations in this evolving field of research.

Creating a novel multiparametric magnetic resonance imaging-based biopsy strategy for reducing unnecessary prostate biopsies: a retrospective cohort study.

Background: The overdiagnosis of prostate cancer (PCa) caused by unnecessary prostate biopsy has become a worldwide problem that urgently requires a solution. We aimed to reduce the unnecessary prostate biopsies and increase the detection rate of clinically significant PCa (csPCa) by creating a novel multiparametric magnetic resonance imaging (mpMRI)-based strategy. Methods: A total of 1,194 eligible patients who underwent transperineal prostate biopsies from January 2018 to December 2022 were included in this retrospective study. Of these patients, 1,080 who received prostate biopsies from January 2018 to July 2022 were regarded as cohort 1 for primary analysis, and 114 patients who received prostate biopsies from August 2022 to December 2022 were collected in cohort 2 for validation. All the mpMRI images were quantitatively evaluated by the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v. 2.1). The diagnostic performances were assessed through the receiver operating characteristic (ROC) curve and area under the curve (AUC) and were compared with the DeLong test. Cancer diagnosis-free survival analysis was performed using the Kaplan-Meier method and log-rank test. The primary endpoint of this study was clinically significant PCa with an International Society of Urological Pathology (ISUP) grade ≥2. Results: In cohort 1, the results of ROC curves demonstrated that the PI-RADS score had a higher diagnostic accuracy (AUC =0.898 for any-grade PCa; AUC =0.917 for csPCa) than did the other clinical variables (P<0.001). Under the novel mpMRI-based biopsy strategy, all patients with PI-RADS 1 can safely avoid prostate biopsy. For patients with PI-RADS 2, prostate biopsy should be considered for patients with prostate-specific antigen density (PSAD) ≥0.3 ng/mL2 and prostate volume <65 mL. As for patients with PI-RADS 3, structured surveillance programs can be a viable option if PSAD <0.3 ng/mL2 and prostate volume ≥65 mL. Finally, patients with a PI-RADS score of 4 and 5 should undergo prostate biopsy due to the high probability of clinically significant PCa. In the validation analysis of cohort 2, 48 patients were placed into a biopsy-spared group with no csPCa cases, while 66 patients were placed in a biopsy-needed group, with an csPCa detection rate of 50.0%. Overall, the novel strategy demonstrated a sensitivity, specificity, positive predictive value, and negative predictive value of 98.9%, 57.5%, 50.5%, and 99.2%, respectively, for diagnosing csPCa. Conclusions: An mpMRI-based biopsy strategy can effectively avoid about 40% of prostate biopsies and maintain a high detection rate for clinically significant PCa. It can further provide valuable guidance for patients and physicians in considering the necessity of prostate biopsy.

Comparison of physics-based deformable registration methods for image-guided neurosurgery.

This paper compares three finite element-based methods used in a physics-based non-rigid registration approach and reports on the progress made over the last 15 years. Large brain shifts caused by brain tumor removal affect registration accuracy by creating point and element outliers. A combination of approximation- and geometry-based point and element outlier rejection improves the rigid registration error by 2.5 mm and meets the real-time constraints (4 min). In addition, the paper raises several questions and presents two open problems for the robust estimation and improvement of registration error in the presence of outliers due to sparse, noisy, and incomplete data. It concludes with preliminary results on leveraging Quantum Computing, a promising new technology for computationally intensive problems like Feature Detection and Block Matching in addition to finite element solver; all three account for 75% of computing time in deformable registration.

Association between MTHFR c.677C>T variant and erectile dysfunction among males attending fertility clinic.

ABSTRACT: Genetic risk factors have been shown to contribute to the development of sexual dysfunction. However, the role of methylenetetrahydrofolate reductase (MTHFR) gene variants in the risk of erectile dysfunction (ED) remains unclear. In this study, we recruited 1254 participants who underwent ED assessed by the International Index of Erectile Function-5. The MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction (PCR). No significant difference in the genotypic frequency of the MTHFR C677T polymorphism (CC, CT, and TT) was observed between men from the ED and non-ED groups. In addition, on binary logistic regression analysis, both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T polymorphism. Interestingly, a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED (P = 0.02). The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis, even after adjusting for potential confounders (odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.15-5.50, P = 0.02). These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe ED. Identification of MTHFR gene polymorphisms may provide complementary information for ED patients during routine clinical diagnosis.

Real-Time Dynamic Data Driven Deformable Registration for Image-Guided Neurosurgery: Computational Aspects.

Current neurosurgical procedures utilize medical images of various modalities to enable the precise location of tumors and critical brain structures to plan accurate brain tumor resection. The difficulty of using preoperative images during the surgery is caused by the intra-operative deformation of the brain tissue (brain shift), which introduces discrepancies concerning the preoperative configuration. Intra-operative imaging allows tracking such deformations but cannot fully substitute for the quality of the pre-operative data. Dynamic Data Driven Deformable Non-Rigid Registration (D4NRR) is a complex and time-consuming image processing operation that allows the dynamic adjustment of the pre-operative image data to account for intra-operative brain shift during the surgery. This paper summarizes the computational aspects of a specific adaptive numerical approximation method and its variations for registering brain MRIs. It outlines its evolution over the last 15 years and identifies new directions for the computational aspects of the technique.

[Research research on the use of melatonin in combination with therapeutic hypothermia for the treatment of neonatal hypoxic-ischemic encephalopathy]. / è¤ªé»‘ç´ è”åˆäºšä½Žæ¸©æ²»ç–—æ–°ç”Ÿå„¿ç¼ºæ°§ç¼ºè¡€æ€§è„‘ç— çš„ç ”ç©¶è¿›å±•.

Neonatal hypoxic-ischemic encephalopathy (HIE) remains one of the leading causes of death and long-term neurodevelopmental disorders in full-term neonates, and there is currently no curative treatment. Therapeutic hypothermia is now a standard therapy for HIE in the neonatal intensive care unit, but its safety and efficacy in remote areas remains unclear. Melatonin is an indole endocrine hormone mainly produced by the pineal gland and it has the ability to easily penetrate the blood-brain barrier. Through receptor and non-receptor mechanisms, melatonin exerts anti-oxidative and anti-inflammatory effects and participates in the regulation of organelle function and the inhibition of cell death. Melatonin is considered one of the most promising drugs for the treatment of HIE based on its reliable safety profile and clinical/preclinical results. This article reviews the recent research on the use of melatonin in combination with therapeutic hypothermia for the treatment of neonatal HIE.

Standardized measurement of mid-surface shift of brain based on deep Hough transform.

The measurement of mid-surface shift (MSS), the geometric displacement between the actual mid-surface and the ideal midsagittal plane (iMSP), is of great significance for accurate diagnosis, treatment and prognosis of patients with intracranial hemorrhage (ICH). Most previous studies are subject to inherent inaccuracy on account of calculating midline shift (MLS) based on 2D slices and ignoring pathological conditions. In this study, we propose a novel standardized measurement model to quantify the distance and the overall volume of mid-surface shift (MSS-D, MSS-V). Our work has four highlights. First, we develop an end-to-end network architecture with multiple sub-tasks including the actual mid-surface segmentation, hematoma segmentation and iMSP detection, which significantly improves the efficiency and accuracy of MSS measurement by taking advantage of the common properties among tasks. Second, an efficient iMSP detection scheme is proposed based on the differentiable deep Hough transform (DHT), which converts and simplifies the plane detection problem in the image space into a keypoint detection problem in the Hough space. Third, we devise a sparse DHT strategy and a weighted least square (WLS) method to increase the sparsity of features, improving inference speed and greatly reducing computation cost. Fourth, we design a joint loss function to comprehensively consider the correlation of features between multi-tasks and multi-domains. Extensive validation on our large in-house dataset (519 patients) and the public CQ500 dataset (491 patients), demonstrates the superiority of our method over the state-of-the-art methods.

[Risk factors for neonatal asphyxia and establishment of a nomogram model for predicting neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture: a multicenter study]. / æ¹–åŒ—æ©æ–½åœŸå®¶æ—è‹—æ—è‡ªæ²»å·žæ–°ç”Ÿå„¿çª’æ¯å±é™©å› ç´ åˆ†æžåŠåˆ—çº¿å›¾é¢„æµ‹æ¨¡åž‹çš„æž„å»ºï¼šä¸€é¡¹å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS: The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.

Development and validation of a prognostic model incorporating tumor thrombus grading for nonmetastatic clear cell renal cell carcinoma with tumor thrombus: A multicohort study.

There is significant variability with respect to the prognosis of nonmetastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). By applying multiregion whole-exome sequencing on normal-tumor-thrombus-metastasis quadruples from 33 ccRCC patients, we showed that metastases were mainly seeded by VTT (81.8%) rather than primary tumors (PTs). A total of 706 nonmetastatic ccRCC patients with VTT from three independent cohorts were included in this study. C-index analysis revealed that pathological grading of VTT outperformed other indicators in risk assessment (OS: 0.663 versus 0.501-0.610, 0.667 versus 0.544-0.651, and 0.719 versus 0.511-0.700 for Training, China-Validation, and Poland-Validation cohorts, respectively). We constructed a risk predicting model, TT-GPS score, based on four independent variables: VTT height, VTT grading, perinephric fat invasion, and sarcomatoid differentiation in PT. The TT-GPS score displayed better discriminatory ability (OS, c-index: 0.706-0.840, AUC: 0.788-0.874; DFS, c-index: 0.691-0.717, AUC: 0.771-0.789) than previously reported models in risk assessment. In conclusion, we identified for the first-time pathological grading of VTT as an unheeded prognostic factor. By incorporating VTT grading, the TT-GPS score is a promising prognostic tool in predicting the survival of nonmetastatic ccRCC patients with VTT.

Empirical mode decomposition of the atmospheric flows and pollutant transport over real urban morphology.

The momentum transport and pollutant dispersion in the atmospheric surface layer (ASL) are governed by a broad spectrum of turbulence structures. Whereas, their contributions have not been explicitly investigated in the context of real urban morphology. This paper aims to elucidate the contributions from different types of eddies in the ASL over a dense city to provide the reference of urban planning, realizing more favorable ventilation and pollutant dispersion. The building-resolved large-eddy simulation dataset of winds and pollutants over the Kowloon downtown, Hong Kong, is decomposed into a few intrinsic mode functions (IMFs) via empirical mode decomposition (EMD). EMD is a data-driven algorithm that has been successfully implemented in many research fields. The results show that four IMFs are generally enough to capture most of the turbulence structures in real urban ASL. In particular, the first two IMFs, which are initiated by individual buildings, capture the small-scale vortex packets that populate within the irregular building clusters. On the other hand, the third and fourth IMFs capture the large-scale motions (LSMs) detached to the ground surface that are highly efficient in transport. They collectively contribute to nearly 40% of vertical momentum transport even with relatively low vertical turbulence kinetic energy (TKE). LSMs are long, streaky structures that mainly consist of streamwise TKE components. It is found that the open areas and regular streets promote the portion of streamwise TKE in LSMs, improving the vertical momentum transport and pollutant dispersion. In addition, these streaky LSMs are found to play a crucial role in pollutant dilution in the near field after the pollutant source, while the small-scale vortex packets are more efficient in transport in the mid-field and far-field.

Association of BMI with erectile dysfunction: A cross-sectional study of men from an andrology clinic.

Abnormal body mass index (BMI) is associated with an increased risk of erectile dysfunction (ED). However, the relationship between different BMI categories and the levels of ED severity remains unclear. In the current study, 878 men from the andrology clinic in Central China were recruited. Erectile function was assessed by the International Index of Erectile Function (IIEF) scores. Questionnaires included questions about demographic characteristics (age, height, weight, educational status), lifestyle habits (drinking, smoking, sleep time), and medical history. Logistic regression was used to examine the association between ED risk and BMI. The incidence of ED was 53.1%. BMI was significantly higher in men from the ED group than in those from the non-ED group (P = 0.01). Compared with the normal weight group, obese men had a higher risk of ED (OR = 1.97, 95% CI = 1.25-3.14, P = 0.004), even after adjustment for potential confounders (OR = 1.78, 95% CI = 1.10-2.90, P = 0.02). Moreover, the positive correlation between obesity and moderate/severe ED severity was confirmed by logistic regression analysis (moderate/severe ED, OR = 2.71, 95% CI = 1.44-5.04, P = 0.002), even after adjusting for potential confounders (OR = 2.51 95% CI = 1.24-5.09, P = 0.01). Collectively, our findings indicate a positive correlation between obesity and the risk of moderate/severe ED. Clinicians could pay more attention to moderate/severe ED patients to maintain a healthy body weight to improve erectile function.

5-aminolevulinic acid photodynamic therapy combined with wart curettage treatment for intractable urethral condylomata acuminata. A case report.

Condylomata acuminata (CA) is caused by human papillomavirus (HPV). It is one of the most common sexually transmitted diseases (STD). The lesions mainly occur in the external genitalia and perianal areas, rarely involves in urethral and usually localized at the distal 3 cm of the urethral orifice. Because of the special anatomical site, treating urethral CA is challenging and it has high recurrence rate after treatment. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) can successfully treat urethral CA, however, the experience of using ALA-PDT combined with wart curettage to treat intractable urethral CA is still very limited. In here, we reported an intractable urethral CA case with effective remission after receiving combination therapy. Wart curettage combine with ALA-PDT is an expeditious, economical, and well-tolerated treatment method.

Association between semen collection time and semen parameters: an observational study.

The process of semen collection plays a key role in the quality of semen specimens. However, the association between semen collection time and semen quality is still unclear. In this study, ejaculates by masturbation from 746 subfertile men or healthy men who underwent semen analysis were examined. The median (interquartile range) semen collection time for all participants was 7.0 (5.0-11.0) min, and the median time taken for semen collection was lower in healthy men than that in subfertile men (6.0 min vs 7.0 min). An increase in the time required to produce semen samples was associated with poorer semen quality. Among those undergoing assisted reproductive technology (ART), the miscarriage rate was positively correlated with the semen collection time. After adjusting for confounders, the highest quartile (Q4) of collection time was negatively associated with semen volume and sperm concentration. A longer time to produce semen samples (Q3 and Q4) was negatively correlated with progressive and total sperm motility. In addition, there was a significant negative linear association between the semen collection time and the sperm morphology. Higher risks of asthenozoospermia (adjusted odds ratio [OR] = 2.06, 95% confidence interval [CI]: 1.31-3.25, P = 0.002) and teratozoospermia (adjusted OR = 1.98, 95% CI: 1.10-3.55, P = 0.02) were observed in Q3 than those in Q1. Our results indicate that a higher risk of abnormal semen parameter values was associated with an increase in time for semen collection, which may be related to male fertility through its association with semen quality.

Wavelet analysis of the atmospheric flows over real urban morphology.

Winds are the basic forces for atmospheric transport such as pollutant removal and pedestrian thermal comfort. The transport capability is commonly measured in terms of length and velocity scales. In this connection, the flows in the atmospheric surface layer (ASL) over the Kowloon Peninsula, Hong Kong (HK) are scrutinized by the large-eddy simulation (LES) to characterize the motion scales over real urban morphology. Apart from statistical analysis, the streamwise fluctuating velocity u' is examined by both wavelet and energy spectrum in which a primary peak is consistently shown at streamwise wavelength 70 m ≤ λx ≤ 300 m. A secondary peak at a longer wavelength 800 m ≤ λx ≤ 3000 m, however, is unveiled by wavelet only. It denotes the existence of intermittent turbulence structures whose sizes are much larger than those of buildings. Further wavelet analysis reveals that majority energy-carrying eddies are enlarging (tens to hundreds of meters) from the roughness sublayer (RSL) to the inertial sublayer (ISL). Analogous to its smooth-wall and schematic rough-wall counterparts, the turbulence kinetic energy (TKE) over urban areas is peaked in the ISL which is carried by eddies of size 50 m ≤ λx ≤ 1000 m. The (horizontal) spatial distribution of energy-carrying eddies is further visualized to compare the crucial motion scales in the RSL and ISL. Finally, conditional sampling is used to demystify the contribution to vertical momentum flux u'w' in terms of streamwise wavelength and quadrants. The results advance our fundamental understanding of ASL transport processes, fostering sustainable environmental policy.

Homeodomain protein HOMEZ is dispensable for male fertility in mice.

Background: Homeodomain (HD) proteins contain an evolutionarily conserved helix-turn-helix (HTH) DNA-binding motif and act as transcription factors to control gene expression. A previous study showed that the HD gene Homez is highly enriched in adult testes. However, the role of HOMEZ in spermatogenesis and male fertility remains unknown. Methods: Using CRISPR/Cas9 technology, Homez mutant mice were generated and performed histological, immunofluorescence, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot and mating assays to analyze the phenotype of Homez mutants. Results: Molecular phylogenetic analyses indicated that the HOMEZ is evolutionarily conserved among mammalian species. qRT-PCR and Western blot analyses showed that Homez is highly expressed in the testis, with a relatively increased expression trend during spermatogenesis. Homez mutant males were viable and showed no differences in body and testis weight compared to their wild-type. In addition, mating between Homez mutant males and wild-type females produced normal litter sizes. Moreover, histopathology detected complete spermatogenesis in the seminiferous tubules and mature spermatozoa in the epididymides from Homez knockout males. Furthermore, significantly increased transcription of three Zhx genes were found in Homez mutatnt testes compared with wild-type testes. Conclusions: Homez knockout mice are fertile and are not essential for germ cell development. These findings could prevent unnecessary duplicative work by other groups.

Cyanidin-3-Ο-glucoside supplementation in cryopreservation medium improves human sperm quality.

Currently, the cryopreservation of human spermatozoa must overcome the adverse effects of excessive oxidation. In this study, we aimed to evaluate the effect of supplementation of cryopreservation medium with cyanidin-3-Ο-glucoside (C3G) on sperm quality. Semen samples were obtained from men with normozoospermia according to WHO criteria (n = 39). The sperm parameter values were compared after cryopreservation in medium supplemented with and without C3G.Compared with the control group (without additive), low doses (50 µM and 100 µM) of C3G improved sperm viability and motility and decreased the reactive oxygen species (ROS) of spermatozoa, while high doses (200 µM) of C3G did not obviously enhance sperm quality. The amount of DNA fragmentation index (DFI) and high DNA stainability (HDS) after freezing were higher in the control group than in the C3G supplementation groups. Low-concentration C3G supplementation (50 µM) was negatively correlated with sperm ROS levels (r = -0.2, p = 0.03). Collectively, our findings suggest that C3G could be an efficient semen cryoprotectant that ameliorates oxidative stress in human sperm during cryopreservation.

Defining Delayed Perihematomal Edema Expansion in Intracerebral Hemorrhage: Segmentation, Time Course, Risk Factors and Clinical Outcome.

We attempt to generate a definition of delayed perihematomal edema expansion (DPE) and analyze its time course, risk factors, and clinical outcomes. A multi-cohort data was derived from the Chinese Intracranial Hemorrhage Image Database (CICHID). A non-contrast computed tomography (NCCT) -based deep learning model was constructed for fully automated segmentation hematoma and perihematomal edema (PHE). Time course of hematoma and PHE evolution correlated to initial hematoma volume was volumetrically assessed. Predictive values for DPE were calculated through receiver operating characteristic curve analysis and were tested in an independent cohort. Logistic regression analysis was utilized to identify risk factors for DPE formation and poor outcomes. The test cohort's Dice scores of lesion segmentation were 0.877 and 0.642 for hematoma and PHE, respectively. Overall, 1201 patients were enrolled for time-course analysis of ICH evolution. A total of 312 patients were further selected for DPE analysis. Time course analysis showed the growth peak of PHE approximately concentrates in 14 days after onset. The best cutoff for DPE to predict poor outcome was 3.34 mL of absolute PHE expansion from 4-7 days to 8-14 days (AUC=0.784, sensitivity=72.2%, specificity=81.2%), and 3.78 mL of absolute PHE expansion from 8-14 days to 15-21 days (AUC=0.682, sensitivity=59.3%, specificity=92.1%) in the derivation sample. Patients with DPE was associated with worse outcome (OR: 12.340, 95%CI: 6.378-23.873, P<0.01), and the larger initial hematoma volume (OR: 1.021, 95%CI: 1.000-1.043, P=0.049) was the significant risk factor for DPE formation. This study constructed a well-performance deep learning model for automatic segmentations of hematoma and PHE. A new definition of DPE was generated and is confirmed to be related to poor outcomes in ICH. Patients with larger initial hematoma volume have a higher risk of developing DPE formation.

Knockout of cyclin B1 in granulosa cells causes female subfertility.

In mammalian cells, cyclin B1 plays a pivotal role in mitotic and meiotic progression. It has been reported that infertility occurs after disruption of cyclin B1 (Ccnb1) in male germ cells and oocytes. However, it remains to be elucidated whether the specific disruption of Ccnb1 in granulosa cells influences the reproductive activity of female mice. Amhr2 is expressed in granulosa cells (GCs) of the ovary. Here, we mated Ccnb1Flox/Flox mice with a transgenic mouse strain expressing Amhr2-Cre to generate GC-specific Ccnb1 knockout mice. The results showed that Ccnb1 Flox/Flox, Amhr2-Cre (Ccnb1 cKO) mice were subfertile but had normal oocyte meiotic progress, spindle shape and protein levels of cohesin subunits REC8 and SMC3 on arm chromosomes during meiosis I. A further study found that 32.4% of oocytes from Ccnb1 cKO mice exhibited chromosome condensation and spindle disassembly after the first polar body extrusion and failed to undergo second meiosis, which was never found in oocytes from Ccnb1Flox/Flox mice. In addition, the percentages of 2-cell embryos, morulas, and blastocysts in the Ccnb1 mutant group were all dramatically decreased compared to those in the Ccnb1Flox/Flox group (39.2% vs. 86.8%, 26.0% vs. 85.0%, 19.1% vs. 85.8%, respectively). Therefore, GC-specific Ccnb1 deletion in mice could cause fewer and poor-quality blastocysts and subsequent subfertility, which plays an important role in understanding the function of cyclin B1 in reproduction.

Extracellular HSPs: The Potential Target for Human Disease Therapy.

Heat shock proteins (HSPs) are highly conserved stress proteins known as molecular chaperones, which are considered to be cytoplasmic proteins with functions restricted to the intracellular compartment, such as the cytoplasm or cellular organelles. However, an increasing number of observations have shown that HSPs can also be released into the extracellular matrix and can play important roles in the modulation of inflammation and immune responses. Recent studies have demonstrated that extracellular HSPs (eHSPs) were involved in many human diseases, such as cancers, neurodegenerative diseases, and kidney diseases, which are all diseases that are closely linked to inflammation and immunity. In this review, we describe the types of eHSPs, discuss the mechanisms of eHSPs secretion, and then highlight their functions in the modulation of inflammation and immune responses. Finally, we take cancer as an example and discuss the possibility of targeting eHSPs for human disease therapy. A broader understanding of the function of eHSPs in development and progression of human disease is essential for developing new strategies to treat many human diseases that are critically related to inflammation and immunity.

Automatic Brain Midline Surface Delineation on 3D CT Images With Intracranial Hemorrhage.

Brain midline delineation plays an important role in guiding intracranial hemorrhage surgery, which still remains a challenging task since hemorrhage shifts the normal brain configuration. Most previous studies detected brain midline on 2D plane and did not handle hemorrhage cases well. We propose a novel and efficient hemisphere-segmentation framework (HSF) for 3D brain midline surface delineation. Specifically, we formulate the brain midline delineation as a 3D hemisphere segmentation task, and employ an edge detector and a smooth regularization loss to generate the midline surface. We also introduce a distance-weighted map to keep the attention on the midline. Furthermore, we adopt rectification learning to handle various head poses. Finally, considering the complex situation of ventricle break-in for hemorrhages in bilateral intraventricular (B-IVH) cases, we identify those cases via a classification model and design a midline correction strategy to locally adjust the midline. To our best knowledge, it is the first study focusing on delineating the brain midline surface on 3D CT images of hemorrhage patients and handling the situation of ventricle break-in. Extensive validation on our large in-house datasets (519 patients) and the public CQ500 dataset (491 patients), demonstrates that our method outperforms state-of-the-art methods on brain midline delineation.