Hand skeletal features of children and adolescents with different growth statuses and periods.

Background: The hand skeletal features of children and adolescents at different growth statuses and development periods, and the correlation between these skeletal features and hand asymmetric force are currently unclear. Thus, this study sought to investigate the hand skeletal features of children and adolescents at different growth statuses and at different periods of development, and the correlation between these skeletal features and asymmetric force in hands. Methods: A retrospective study was performed on subjects aged 4-20 years with good growth status (group A) or short stature (group B). Additional subjects aged 4-20, 21-40, and >40 years were enrolled in groups C, D, and E, respectively. All the subjects underwent left-hand posteroanterior X-ray radiography. Brachymesophalangia-V (BMP-V), conical epiphysis, epiphysis/metaphysis symmetry of the proximal phalanx (ESP), and the angle of the metacarpal-phalangeal axis were analyzed. Results: Of the 654 children and teenagers aged 4-20 years (median: 11 years) enrolled in the study, 432 were allocated to group A, of whom 237 (54.9%) were male and 195 (45.1%) were female, and 222 matched cases were allocated to group B, of whom 112 (50.5%) were male and 110 (49.5%) were female. The first to third ESPs were significantly (P<0.05) greater in group A than in group B, while the first to third angles of the metacarpal-phalangeal axis were significantly (P<0.05) smaller in group A than in group B. The correlation analysis revealed a highly significant (P<0.01) negative correlation between the ESP and angle of the metacarpal-phalangeal axis (r=-0.948, -0.926, -0.940, -0.885, and -0.848, respectively). The incidence of BMP-V was 15.4% in all patients, while that of conical epiphysis was 19.5%. The incidence of BMP-V and conical epiphysis was significantly (P<0.05) smaller in group A than in group B (11.1% vs. 23.8% for BMP-V and 16.6% vs. 25.2% for conical epiphysis, respectively). Additionally, 216 subjects were enrolled in group C (108 male and 108 female), 185 subjects were enrolled in in group D (93 male and 92 female), and 176 subjects were enrolled in in group E (104 male and 72 female). The second to fifth ESPs in group C were significantly (P<0.05) smaller than those in both groups D and E, while the second to fifth angles of the metacarpal-phalangeal axis were significantly (P<0.05) larger in group C than in both groups D and E. A BMP-V was present in 35 (16.2%) patients in group C, 8 (4.3%) in group D, and 2 (1.1%) in group E, and the difference among the three groups was statistically significant (P<0.05). Conclusions: The epiphyseal symmetry of the proximal phalanges is poor in short stature children and adolescents, and the angle between the metacarpal and phalangeal axes is larger in children and adolescents with short stature than those with normal height and good growth status. A negative correlation was found between the epiphyseal symmetry of the proximal phalanges and asymmetrical stress.

Targeting pro-inflammatory T cells as a novel therapeutic approach to potentially resolve atherosclerosis in humans.

Atherosclerosis (AS), a leading cause of cardio-cerebrovascular disease worldwide, is driven by the accumulation of lipid contents and chronic inflammation. Traditional strategies primarily focus on lipid reduction to control AS progression, leaving residual inflammatory risks for major adverse cardiovascular events (MACEs). While anti-inflammatory therapies targeting innate immunity have reduced MACEs, many patients continue to face significant risks. Another key component in AS progression is adaptive immunity, but its potential role in preventing AS remains unclear. To investigate this, we conducted a retrospective cohort study on tumor patients with AS plaques. We found that anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) significantly reduces AS plaque size. With multi-omics single-cell analyses, we comprehensively characterized AS plaque-specific PD-1+ T cells, which are activated and pro-inflammatory. We demonstrated that anti-PD-1 mAb, when captured by myeloid-expressed Fc gamma receptors (FcγRs), interacts with PD-1 expressed on T cells. This interaction turns the anti-PD-1 mAb into a substitute PD-1 ligand, suppressing T-cell functions in the PD-1 ligands-deficient context of AS plaques. Further, we conducted a prospective cohort study on tumor patients treated with anti-PD-1 mAb with or without Fc-binding capability. Our analysis shows that anti-PD-1 mAb with Fc-binding capability effectively reduces AS plaque size, while anti-PD-1 mAb without Fc-binding capability does not. Our work suggests that T cell-targeting immunotherapy can be an effective strategy to resolve AS in humans.

Changes in the airway microbiome in patients with bronchiectasis.

This study used metagenomic next-generation sequencing (mNGS) technology to explore the changes of the microbial characteristics in the lower respiratory tract in patients with acute exacerbations of bronchiectasis (noncystic fibrosis) to guide clinical treatment and improve patients' quality of life and prognosis. This prospective study included 54 patients with acute exacerbation and 46 clinically stable patients admitted to the Respiratory and Critical Care Medicine Center of the People's Hospital of Xinjiang Uygur Autonomous Region from January 2020 to July 2022. Sputum was subjected to routine microbiological tests, and bronchoalveolar lavage fluid (BALF) samples were subjected to microbiological tests and mNGS of BALF before empirical antibiotic therapy. Serum inflammatory markers (white blood cell count, interleukin-6, procalcitonin, and C-reactive protein) were measured. In addition, we evaluated the pathogen of mNGS and compared the airway microbiome composition of patients with acute exacerbation and control patients. The mean age of our cohort was 56 ±â€…15.2 years. Eighty-nine patients had positive results by mNGS. There was a significant difference in the detection of viruses between the groups (χ2 = 6.954, P < .01). The fungal species Candida albicans, Pneumocystis jirovecii, and Aspergillus fumigatus were significantly more common in patients with acute exacerbations (χ2 = 5.98, P = .014). The bacterial species Acinetobacter baumannii, Mycobacterium tuberculosis, Haemophilus influenzae, Haemophilus parahaemolyticus, Abiotrophia defectiva, and Micromonas micros were significantly more prevalent in patients with acute exacerbations (χ2 = 4.065, P = .044). The most common bacterial species isolated from the sputum and BALF samples of patients with acute exacerbation was A. baumannii. Chlamydia psittaci was found in 4 patients. In addition, of 77 patients with negative sputum culture, 66 had positive results by mNGS, demonstrating the increased sensitivity and accuracy of mNGS. Patients with acute exacerbation of bronchiectasis tend to have mixed infections in the lower respiratory tract. The frequency of viruses, fungi, and Mycoplasma was higher in these patients. Our findings suggest that mNGS could be used to identify pathogenic microorganisms in these patients, increasing the effectiveness of antibiotic therapy.

Women with preeclampsia may have reduced risk of breast cancer: a meta-analysis of cohort studies with 7.8 million participants.

This review pooled data from the literature to examine the association between preeclampsia (PE) and subsequent risk of breast cancer in women. Cohort studies published in the databases of PubMed, Embase, Scopus, and Web of Science up to 18 July 2023 were searched. Adjusted data were pooled to obtain the risk ratio (RR). Eleven studies with 15 cohorts and a cumulative sample size of 7,838,693 women were included. Meta-analysis of all studies demonstrated a reduced risk of breast cancer in women with PE as compared to those without PE (RR: 0.89 95% CI: 0.83, 0.95 p < 0.001 I2 = 50%). Follow-up ranged from 8 to 29.2 years. Results did not change during sensitivity analysis. Outcomes varied on subgroup analysis based on location, study type, data extraction method, incidence of breast cancer, and follow-up. To conclude, women with PE may have a reduced risk of breast cancer later in life. However, the risk reduction is minimal and may not have much clinical significance. The evidence is also limited by high inter-study heterogeneity and lack of adjustment of all possible confounders.

Clinical application of modified hip joint lateral position in femoral neck fracture.

BACKGROUND: To show the femoral neck better in hip lateral view of X-ray, we design a modified hip lateral view and then investigate the value in femoral neck fractures. METHODS: CT images of 10 normal hip joints for 3D reconstruction were selected, the Mimics Medical 21.0 was used, and rotating the proximal femur was to find the most suitable angle for showing the femoral neck well, designed the modified lateral view according to this angle. We collected 35 healthy cases and 35 femoral neck fractures as the normal and fracture group. And two groups were all taken hip anteroposterior view, cross-table lateral view and modified lateral view, which were analyzed by two radiologists to score the anatomical structures of the articular surface, femoral head, head neck junction, femoral neck, basal region and intertrochanteric region. Friedman test was used to analyze the score of femoral neck at different angles. T test and Wilcoxon signed-rank test were to compare inter-groups. RESULTS: The modified lateral view was designed as follows: The subjects were supine, with the sagittal axis biased toward the healthy side at an angle of approximately 20° to the long axis of the examination table, the hip joint flexed at 45°, the lower extremity abducted at 40°, the centerline inclined 45° toward the head and the centerline aligned with the center of the groin. The modified lateral view showed the femoral head, head neck junction and femoral neck more clearly than the cross-table lateral view, but the cross-table lateral view showed the femoral neck basal and intertrochanteric region better. In addition, the time of taking the modified lateral view was significantly less than the cross-table lateral view (normal group: 0.789 min ± 0.223 vs 0.623 min ± 0.207, P < 0.001; fracture group: 1.131 min ± 0.362 vs 0.946 min ± 0.390, P < 0.001). CONCLUSIONS: The modified lateral view can obtain a standard sagittal image of femoral neck, which can show the dislocation and angulation of the sagittal femoral neck fracture clearly, and improve the accuracy of diagnosis. And it is more convenient and easier for patients to cooperate, which is worthy promoting and applying in clinical work.

Development of a prognostic model for anoikis and identifies hub genes in hepatocellular carcinoma.

Considering the high fatality of hepatocellular carcinoma (HCC), current prognostic systems are insufficient to accurately forecast HCC patients' outcomes. In our study, nine anoikis­related genes (PTRH2, ITGAV, ANXA5, BIRC5, BDNF, BSG, DAP3, SKP2, and EGF) were determined to establish a risk scoring model using LASSO regression, which could be validated in ICGC dataset. Kaplan-Meier curves and time-dependent receiver operating characteristic (ROC) curve analysis confirmed the risk score possessed an accurate predictive value for the prognosis of HCC patients. The high-risk group showed a higher infiltration of aDCs, macrophages, T-follicular helper cells, and Th2 cells. Besides, PD-L1 was significantly higher in the high-risk group compared to the low-risk group. Several anoikis­related genes, such as ANX5, ITGAV, BDNF and SKP2, were associated with drug sensitivity in HCC. Finally, we identified BIRC5 and SKP2 as hub genes among the nine model genes using WGCNA analysis. BIRC5 and SKP2 were over-expressed in HCC tissues, and their over-expression was associated with poor prognosis, no matter in our cohort by immunohistochemical staining or in the TCGA cohort by mRNA-Seq. In our cohort, BIRC5 expression was highly associated with the T stage, pathologic stage, histologic grade and AFP of HCC patients. In general, our anoikis-related risk model can enhance the ability to predict the survival outcomes of HCC patients and provide a feasible therapeutic strategy for immunotherapy and drug resistance in HCC. BIRC5 and SKP2 are hub genes of anoikis­related genes in HCC.

Images of giant cell tumor and chondroblastoma around the knee: retrospective analysis of 99 cases.

Background: It is difficult to differentiate giant cell tumors of the bone (GCTB) from chondroblastoma around the knee based on imaging findings. This study analyzed the imaging features of these 2 diseases for better differentiation. Methods: This retrospective cross-sectional cohort study reviewed data of patients with pathologically confirmed GCTB (n=81; age 15-75 years; median age 33 years) and chondroblastoma (n=18; age 12-34 years; median age 14 years). In all, 18 imaging signs were analyzed. Results: Patients with chondroblastoma were relatively younger than those with GCTB. On imaging, lesion length was significantly (P<0.00001) smaller in chondroblastoma [range, 15.80-78.30 mm; mean ± standard deviation (SD) 34.15±18.24 mm; 95% confidence interval (CI): 24.05-44.25 mm] than in GCTB [range, 30.10-117.50 mm; mean ± SD 59.73±15.28 mm; 95% CI: 56.24-63.22 mm]. Significantly more (P<0.05) chondroblastoma lesions had calcification (76.5% vs. 1.3%), lobulation (77.8% vs. 32.1%), and swelling range >15 mm (84.6% vs. 41.1%) than did GCTB lesions, whereas significantly more (P<0.05) GCTB lesions were greater than half the host bone diameter (74.1% vs. 16.7%) and had a lesion long axis that was consistent with that of the host bone (98.8% vs. 27.8%). There were no significant differences (P>0.05) between the 2 tumors in the remaining 11 imaging signs. Conclusions: A narrow zone of transition, intratumor calcification, lobulation, tumor transverse diameter greater than the bone diameter, maximum lesion length, consistency between the tumor and bone long axes, and edema range around the lesion >15 mm are parameters that can be used to differentiate GCTB from chondroblastoma around the knee.

A novel adaptive cubic quasi-Newton optimizer for deep learning based medical image analysis tasks, validated on detection of COVID-19 and segmentation for COVID-19 lung infection, liver tumor, and optic disc/cup.

BACKGROUND: Most of existing deep learning research in medical image analysis is focused on networks with stronger performance. These networks have achieved success, while their architectures are complex and even contain massive parameters ranging from thousands to millions in numbers. The nature of high dimension and nonconvex makes it easy to train a suboptimal model through the popular stochastic first-order optimizers, which only use gradient information. PURPOSE: Our purpose is to design an adaptive cubic quasi-Newton optimizer, which could help to escape from suboptimal solution and improve the performance of deep neural networks on four medical image analysis tasks including: detection of COVID-19, COVID-19 lung infection segmentation, liver tumor segmentation, optic disc/cup segmentation. METHODS: In this work, we introduce a novel adaptive cubic quasi-Newton optimizer with high-order moment (termed ACQN-H) for medical image analysis. The optimizer dynamically captures the curvature of the loss function by diagonally approximated Hessian and the norm of difference between previous two estimates, which helps to escape from saddle points more efficiently. In addition, to reduce the variance introduced by the stochastic nature of the problem, ACQN-H hires high-order moment through exponential moving average on iteratively calculated approximated Hessian matrix. Extensive experiments are performed to access the performance of ACQN-H. These include detection of COVID-19 using COVID-Net on dataset COVID-chestxray, which contains 16 565 training samples and 1841 test samples; COVID-19 lung infection segmentation using Inf-Net on COVID-CT, which contains 45, 5, and 5 computer tomography (CT) images for training, validation, and testing, respectively; liver tumor segmentation using ResUNet on LiTS2017, which consists of 50 622 abdominal scan images for training and 26 608 images for testing; optic disc/cup segmentation using MRNet on RIGA, which has 655 color fundus images for training and 95 for testing. The results are compared with commonly used stochastic first-order optimizers such as Adam, SGD, and AdaBound, and recently proposed stochastic quasi-Newton optimizer Apollo. In task detection of COVID-19, we use classification accuracy as the evaluation metric. For the other three medical image segmentation tasks, seven commonly used evaluation metrics are utilized, that is, Dice, structure measure, enhanced-alignment measure (EM), mean absolute error (MAE), intersection over union (IoU), true positive rate (TPR), and true negative rate. RESULTS: Experiments on four tasks show that ACQN-H achieves improvements over other stochastic optimizers: (1) comparing with AdaBound, ACQN-H achieves 0.49%, 0.11%, and 0.70% higher accuracy on the COVID-chestxray dataset using network COVID-Net with VGG16, ResNet50 and DenseNet121 as backbones, respectively; (2) ACQN-H has the best scores in terms of evaluation metrics Dice, TPR, EM, and MAE on COVID-CT dataset using network Inf-Net. Particularly, ACQN-H achieves 1.0% better Dice as compared to Apollo; (3) ACQN-H achieves the best results on LiTS2017 dataset using network ResUNet, and outperforms Adam in terms of Dice by 2.3%; (4) ACQN-H improves the performance of network MRNet on RIGA dataset, and achieves 0.5% and 1.0% better scores on cup segmentation for Dice and IoU, respectively, compared with SGD. We also present fivefold validation results of four tasks. It can be found that the results on detection of COVID-19, liver tumor segmentation and optic disc/cup segmentation can achieve high performance with low variance. For COVID-19 lung infection segmentation, the variance on test set is much larger than on validation set, which may due to small size of dataset. CONCLUSIONS: The proposed optimizer ACQN-H has been validated on four medical image analysis tasks including: detection of COVID-19 using COVID-Net on COVID-chestxray, COVID-19 lung infection segmentation using Inf-Net on COVID-CT, liver tumor segmentation using ResUNet on LiTS2017, optic disc/cup segmentation using MRNet on RIGA. Experiments show that ACQN-H can achieve some performance improvement. Moreover, the work is expected to boost the performance of existing deep learning networks in medical image analysis.

Enhanced Catalytic Soot Oxidation over Co-Based Metal Oxides: Effects of Transition Metal Doping.

A series of Co-M (M = Fe, Cr, and Mn) catalysts were synthesized by the sol-gel method for soot oxidation in a loose contact mode. The Co-Fe catalyst exhibited the best catalytic activity among the tested samples, with the characteristic temperatures (T10, T50, and T90) of 470 °C, 557 °C, and 602 °C, respectively, which were 57 °C, 51 °C, and 51 °C lower than those of the CoOx catalyst. Catalyst characterizations of N2 adsorption-desorption, X-ray diffraction (XRD), X-ray photo-electron spectrometry (XPS), and the temperature programmed desorption of O2 (O2-TPD) were performed to gain insights into the relationships between the activity of catalytic soot oxidation and the catalyst properties. The content of Co2+ (68.6%) increased due to the interactions between Co and Fe, while the redox properties and the relative concentration of surface oxygen adsorption (51.7%) were all improved, which could significantly boost the activity of catalytic soot oxidation. The effects of NO and contact mode on soot oxidation were investigated over the Co-Fe catalyst. The addition of 1000 ppm of NO led to significant reductions in T10, T50, and T90 by 92 °C, 106 °C, and 104 °C, respectively, compared to the case without the NO addition. In the tight contact mode, the soot oxidation was accelerated over the Co-Fe catalyst, resulting in 46 °C, 50 °C, and 50 °C reductions in T10, T50, and T90 compared to the loose contact mode. The comparison between real soot and model Printex-U showed that the T50 value of real soot (455 °C) was 102 °C lower than the model Printex-U soot.

A novel prognostic 7-methylguanosine signature reflects immune microenvironment and alternative splicing in glioma based on multi-omics analysis.

Glioma is the most common type of central nervous system tumor with increasing incidence. 7-methylguanosine (m7G) is one of the diverse RNA modifications that is known to regulate RNA metabolism and its dysregulation was associated with various cancers. However, the expression pattern of m7G regulators and their roles in regulating tumor immune microenvironments (TIMEs) as well as alternative splicing events (ASEs) in glioma has not been reported. In this study, we showed that m7G regulators displayed a close correlation with each other and most of them were differentially expressed between normal and glioma tissues. Two m7G signatures were then constructed to predict the overall survival of both GBM and LGG patients with moderate predictive performance. The risk score calculated from the regression coefficient and expression level of signature genes was proved to be an independent prognostic factor for patients with LGG, thus, a nomogram was established on the risk score and other independent clinical parameters to predict the survival probability of LGG patients. We also investigated the correlation of m7G signatures with TIMEs in terms of immune scores, expression levels of HLA and immune checkpoint genes, immune cell composition, and immune-related functions. While exploring the correlation between signature genes and the ASEs in glioma, we found that EIF4E1B was a key regulator and might play dual roles depending on glioma grade. By incorporating spatial transcriptomic data, we found a cluster of cells featured by high expression of PTN exhibited the highest m7G score and may communicate with adjacent cancer cells via SPP1 and PTN signaling pathways. In conclusion, our work brought novel insights into the roles of m7G modification in TIMEs and ASEs in glioma, suggesting that evaluation of m7G in glioma could predict prognosis. Moreover, our data suggested that blocking SPP1 and PTN pathways might be a strategy for combating glioma.

Upconversion nanoparticles regulated drug & gas dual-effective nanoplatform for the targeting cooperated therapy of thrombus and anticoagulation.

Thromboembolism is the leading cause of cardiovascular mortality. Currently, for the lack of targeting, short half-life, low bioavailability and high bleeding risk of the classical thrombolytic drugs, pharmacological thrombolysis is usually a slow process based on micro-pumping. In addition, frequently monitoring and regulating coagulation functions are also required during (and after) the process of thrombolysis. To address these issues, a targeted thrombolytic and anticoagulation nanoplatform (UCATS-UK) is developed based on upconversion nanoparticles (UCNPs) that can convert 808 or 980 nm near-infrared (NIR) light into UV/blue light. This nanoplatform can target and enrich in the thrombus site. Synergistic thrombolysis and anticoagulation therapy thus could be realized through the controlled release of urokinase (UK) and nitric oxide (NO). Both in vitro and in vivo experiments have confirmed the excellent thrombolytic and anticoagulative capabilities of this multifunctional nanoplatform. Combined with the unique fluorescent imaging capability of UCNPs, this work is expected to contribute to the development of clinical thrombolysis therapy towards an integrated system of imaging, diagnosis and treatment.

Structural basis of tethered agonism of the adhesion GPCRs ADGRD1 and ADGRF1.

Adhesion G protein-coupled receptors (aGPCRs) are essential for a variety of physiological processes such as immune responses, organ development, cellular communication, proliferation and homeostasis1-7. An intrinsic manner of activation that involves a tethered agonist in the N-terminal region of the receptor has been proposed for the aGPCRs8,9, but its molecular mechanism remains elusive. Here we report the G protein-bound structures of ADGRD1 and ADGRF1, which exhibit many unique features with regard to the tethered agonism. The stalk region that proceeds the first transmembrane helix acts as the tethered agonist by forming extensive interactions with the transmembrane domain; these interactions are mostly conserved in ADGRD1 and ADGRF1, suggesting that a common stalk-transmembrane domain interaction pattern is shared by members of the aGPCR family. A similar stalk binding mode is observed in the structure of autoproteolysis-deficient ADGRF1, supporting a cleavage-independent manner of receptor activation. The stalk-induced activation is facilitated by a cascade of inter-helix interaction cores that are conserved in positions but show sequence variability in these two aGPCRs. Furthermore, the intracellular region of ADGRF1 contains a specific lipid-binding site, which proves to be functionally important and may serve as the recognition site for the previously discovered endogenous ADGRF1 ligand synaptamide. These findings highlight the diversity and complexity of the signal transduction mechanisms of the aGPCRs.

Clinical and Imaging Features of Desmoplastic Fibroma of Bone for Correct Diagnosis and Differentiation.

OBJECTIVE: The objective of this study is to analyze the clinical and imaging features of desmoplastic fibroma of bone (DFB) for correct diagnosis. MATERIALS AND METHODS: Twenty patients with DFB confirmed by pathology were enrolled, and the imaging presentations were analyzed. Among 20 patients, plain X-ray was performed in all patients, computed tomography (CT) was performed in 12, and magnetic resonance imaging (MRI) was conducted on eight. The clinical and imaging presentations were analyzed and classified to assist in correct diagnosis. RESULTS: Twenty patients with DFB were retrieved, including eleven males and nine females with an age range of 2-52 years (median 27). The DFB involved the femur in six patients, ilium in five, tibia in four, humerus in two, lumbar vertebra in one, radius in one, and calcaneus in the remaining one. DFB was common in the metaphysis of long bones and could involve the diaphysis and epiphysis. The imaging presentations were divided into four types: the cystic expansile destruction in ten patients, osteolytic destruction in five, mixed destruction in four, and paraosseous destruction in one. CT value was 30 -60 Hu in the lesion area (6 cases CT value45Hu). In eight patients with MRI scanning, the lesion in five patients presented with unevenly equal or low signal on T1WI and unevenly equal or high signal on T2WI, with irregular stripes or patches of low signal on both T1WI and T2WI. In the rest three patients, the lesion was evenly equal or low signal on T1WI and evenly high signal on T2WI. MRI more clearly showed a mass in the adjacent soft tissue and the range of edema in the DFB lesion. CONCLUSION: DFB is a rare tumor with strong local aggressiveness, cystic bone destruction, formation of tumor bone trabeculae, soft tissue masses on imaging presentations, low signals on T1WI and T2WI in the lesion, but no periosteal reaction or calcification, which are helpful for diagnosis of the disease and differentiation from other ones.

Long noncoding RNA LUCAT1 enhances the survival and therapeutic effects of mesenchymal stromal cells post-myocardial infarction.

Mesenchymal stromal cell (MSC) transplantation has been a promising therapeutic strategy for repairing heart tissues post-myocardial infarction (MI). Nevertheless, its therapeutic efficacy remains low, which is mainly ascribed to the low viability of transplanted MSCs. Recently, long noncoding RNAs (lncRNAs) have been reported to participate in diverse physiological and pathological processes, but little is known about their role in MSC survival. Using unbiased transcriptome profiling of hypoxia-preconditioned MSCs (HP-MSCs) and normoxic MSCs (N-MSCs), we identified a lncRNA named lung cancer-associated transcript 1 (LUCAT1) under hypoxia. LUCAT1 knockdown reduced the survival of engrafted MSCs and decreased the MSC-based therapeutic potency, as shown by impaired cardiac function, reduced cardiomyocyte survival, and increased fibrosis post-MI. Conversely, LUCAT1 overexpression had the opposite results. Mechanistically, LUCAT1 bound with and recruited jumonji domain-containing 6 (JMJD6) to the promoter of forkhead box Q1 (FOXQ1), which demethylated FOXQ1 at H4R3me2(s) and H3R2me2(a), thus downregulating Bax expression and upregulating Bcl-2 expression to attenuate MSC apoptosis. Therefore, our findings revealed the protective effects of LUCAT1 on MSC apoptosis and demonstrated that the LUCAT1-mediated JMJD6-FOXQ1 pathway might represent a novel target to potentiate the therapeutic effect of MSC-based therapy for ischemic cardiovascular diseases.

Two new pyrone derivatives from the mangrove-derived endophytic fungus Aspergillus sydowii #2B.

Two new pyrone derivatives, 2-(12S-hydroxypropyl)-3-hydroxy-methyl-6-hydroxy-7-methoxychromone (1), and (±)-pyrenocine S (5), together with five known compounds xanthoradone A (2), (+)-3,3',7,7',8,8'-hexahydroxy-5,5'-dimethyl-bianthra-quinone (3), butyrolactone-I (4), pyrenocine A (6), and (±)-pyrenocine E (7) were obtained from the mangrove endophytic fungus Aspergillus sydowii #2B. Their structures were elucidated on the basis of spectroscopic methods, single-crystal X-ray diffraction analysis and comparison data with of literatures. Compounds 2, 3, 4, 5, 6 and 7 showed cytotoxicities against prostate cancer VCaP cells with IC50 values of 4.19 ± 1.02, 33.36 ± 1.42, 1.92 ± 0.82, 20.06 ± 2.01, 7.92 ± 0.86, and 10.13 ± 0.88 µM respectively, while compound 1 showed no cytotoxic activity. Compounds 1, 3, 6, and 7 exhibited weak inhibition effects against the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW 246.7 cells with IC50 values of 40.15, 28.69, 25.25 and 43.08 µM respectively.

Clinical and Imaging Features of Tumors in the Scapula.

BACKGROUND: The scapula is a small irregular-shaped flat bone, which may suffer from a variety of tumors or tumor-like lesions. As the imaging manifestations are complex and changeable, correct imaging diagnosis is difficult. INTRODUCTION: At present, there are few related radiology literatures, and it is necessary to fully analyze the imaging signs of different types of benign and malignant tumors in scapula to guide clinical treatment. This study was to investigate clinical and imaging presentations of tumors and tumor- like lesions in the scapula so as to increase the diagnostic accuracy of diseases in the scapula. METHODS: Patients with scapular tumors confirmed by pathology were enrolled. The imaging and clinical data were analyzed. RESULTS: Among 108 patients, benign tumors were in 53 (49.1%) cases, intermediate in seven (6.5%), and malignant in 48 (44.4%) involving 16 diseases. Osteochondroma was the first benign tumors in 45 cases accounting for 84.9% of all benign scapular tumors, followed by chondroma in four cases (7.5%). The intermediate tumors were mainly eosinophilic granuloma in four cases. Metastatic tumors were the commonest malignant tumor (27 cases or 56.2% of all malignant tumors), followed by chondrosarcoma (in 13 cases). Except for the one case of chondroblastoma in which the lesion involved the glenoid cavity, all the other cartilaginous tumors were located in the scapular body and processes. The type of lesions in the bony processes is the same as in the scapular body, the common lesions in the central area of the body were malignant tumors, and the commonest lesions in the glenoid area were metastasis. Common imaging features of malignant scapular tumors were ill-defined margins, cortical destruction and soft tissue involvement. The imaging features of chondrosarcoma lack specificity except for calcification. Benign lesions usually had a clear boundary and marginal sclerosis. CONCLUSION: A wide variety of benign and malignant tumors may occur in the scapula with mostly cartilaginous and metastatic tumors, and the location and distribution of lesions are similar in the scapula to those in the long bones.

Long-non-coding RNA RUSC1-AS1 accelerates osteosarcoma development by miR-101-3p-mediated Notch1 signalling pathway.

BACKGROUND: Long non-coding RNA (lncRNA) RUSC1-AS1 has been found to modulate several cancers development. In this study, we explored the role of RUSC1-AS1 on osteosarcoma (OS) progression. METHODS: Quantitative Real-time PCR (qRT-PCR) was conducted to test the relative expression of RUSC1-AS1, Notch1 mRNA and miR-101-3p in OS tissues and adjacent normal tissues. Gain- or loss- of functional assays were carried out to determine the roles of RUSC1-AS1 and miR-101-3p in OS progression both in vitro and in vivo. The expression of E-cadherin, N-cadherin, Vimentin, Snail, Notch1, Ras and ERK was determined by Western blot. Furthermore, the relationships between RUSC1-AS1 and miR-101-3p, Notch1 and miR-101-3p were confirmed through RNA immunoprecipitation (RIP) and dual luciferase reporter gene assay. RESULTS: RUSC1-AS1 and Notch1 were up-regulated in OS cells and tissues. Down-regulating RUSC1-AS1 significantly attenuated the proliferative, epithelial-mesenchymal transition (EMT), growth, lung metastasis, migrative and invasive abilities of MG-63 and Saos-2 cells, and aggravated apoptosis, accompanied with down-regulated Notch1-Ras-ERK1/2 in those cells both in vitro and in vivo, while overexpression of RUSC1-AS1 exerted opposite effects. Overexpressing miR-101-3p in OS cells had similar effects as RUSC1-AS1 inhibition. In addition, RUSC1-AS1 functioned as a competing endogenous RNA (ceRNA) to competitively sponge miR-101-3p, thus upregulating Notch1 expression and mediating the malignant behaviors of OS cells. CONCLUSION: RUSC1-AS1 is a novel oncogenic lncRNA in OS through the miR-101-3p-Notch1-Ras-ERK pathway, which might be a potential therapeutic target for OS.

A Novel Human Long Noncoding RNA SCDAL Promotes Angiogenesis through SNF5-Mediated GDF6 Expression.

Angiogenesis is essential for vascular development. The roles of regulatory long noncoding RNAs (lncRNAs) in mediating angiogenesis remain under-explored. Human embryonic stem cell-derived mesenchymal stem cells (hES-MSCs) are shown to exert more potent cardioprotective effects against cardiac ischemia than human bone marrow-derived MSCs (hBM-MSCs), associated with enhanced neovascularization. The purpose of this study is to search for angiogenic lncRNAs enriched in hES-MSCs, and investigate their roles and mechanisms. AC103746.1 is one of the most highly expressed intergenic lncRNAs detected in hES-MSCs versus hBM-MSCs, and named as SCDAL (stem cell-derived angiogenic lncRNA). SCDAL knockdown significantly reduce the angiogenic potential and reparative effects of hES-MSCs in the infarcted hearts, while overexpression of SCDAL in either hES-MSCs or hBM-MSCs exhibits augmented angiogenesis and cardiac function recovery. Mechanistically, SCDAL induces growth differentiation factor 6 (GDF6) expression via direct interaction with SNF5 at GDF6 promoter. Secreted GDF6 promotes endothelial angiogenesis via non-canonical vascular endothelial growth factor receptor 2 activation. Furthermore, SCDAL-GDF6 is expressed in human endothelial cells, and directly enhances endothelial angiogenesis in vitro and in vivo. Thus, these findings uncover a previously unknown lncRNA-dependent regulatory circuit for angiogenesis. Targeted intervention of the SCDAL-GDF6 pathway has potential as a therapy for ischemic heart diseases.

Small extracellular vesicles containing miR-486-5p promote angiogenesis after myocardial infarction in mice and nonhuman primates.

Stem cell-derived small extracellular vesicles (sEVs) promote angiogenesis after myocardial infarction (MI). However, the components of sEVs that contribute to these effects and the safety and efficiency of engineered sEV treatment for MI remain unresolved. Here, we observed improved cardiac function, enhanced vascular density, and smaller infarct size in mice treated with the sEVs from hypoxia-preconditioned (HP) mesenchymal stem cells (MSCs) (HP-sEVs) than in mice treated with normoxia-preconditioned (N) MSCs (N-sEVs). MicroRNA profiling revealed a higher abundance of miR-486-5p in HP-sEVs than in N-sEVs, and miR-486-5p inactivation abolished the benefit of HP-sEV treatment, whereas miR-486-5p up-regulation enhanced the benefit of N-sEV treatment. Matrix metalloproteinase 19 (MMP19) abundance was lower in HP-sEV-treated than N-sEV-treated mouse hearts but was enriched in cardiac fibroblasts (CFs), and Mmp19 was identified as one of the target genes of miR-486-5p. Conditioned medium from CFs that overexpressed miR-486-5p or silenced MMP19 increased the angiogenic activity of endothelial cells; however, medium from CFs that simultaneously overexpressed Mmp19 and miR-486-5p abolished this effect. Mmp19 silencing in CFs reduced the cleavage of extracellular vascular endothelial growth factor (VEGF). Furthermore, miR-486-5p-overexpressing N-sEV treatment promoted angiogenesis and cardiac recovery without increasing arrhythmia complications in a nonhuman primate (NHP) MI model. Collectively, this study highlights the key role of sEV miR-486-5p in promoting cardiac angiogenesis via fibroblastic MMP19-VEGFA cleavage signaling. Delivery of miR-486-5p-engineered sEVs safely enhanced angiogenesis and cardiac function in an NHP MI model and may promote cardiac repair.

Imaging features of hemangioma in long tubular bones.

BACKGROUND: To investigate the imaging features of hemangiomas in long tabular bones for better diagnosis. METHODS: Twenty-four patients with long bone hemangiomas confirmed by pathology were enrolled. Nineteen patients had plain radiography, fourteen patients had computed tomography (CT) and eleven had magnetic resonance imaging (MRI). The hemangioma was divided into medullary [13], periosteal [6] and intracortical type [5]. RESULTS: Among 19 patients with plain radiography, eleven patients were medullary, three periosteal, and five intracortical. In the medullary type, the lesion was primarily osteolytic, including five cases with irregular and unclear rims and one lesion having osteosclerotic and unclear rims. In three patients with the periosteal type, the lesion had clear rims with involvement of the cortical bone in the form of bone defect, including two cases with local thickened bone periosteum and one case having expansile periosteum. Five intracortical hemangiomas had intracortical osteolytic lesions with clear margins. Among 14 patients with CT imaging, 8 cases were medullary, three periosteal, and three intracortical. Among 8 medullary hemangiomas, one had ground glass opacity, and seven had osteolytic, expansile lesions like soft tissue density with no calcification. In three periosteal cases, the lesion was osteolytic with thickened periosteum and narrowed medullary cavity. In three intracortical hemangiomas, the lesion was of even soft tissue density with no calcification. Among 11 patients with MRI imaging, seven were medullary, two periosteal, and two intracortical. Among 7 medullary lesions, six were of hypointense signal on T1WI and hyperintensesignal on T2 WI. In two periosteal cases, the periosteum was thickened, with one case being of equal signal, and the other having no signal. Two intracortical hemangiomas were both of slightly low signal on T1WI but hyperintense signal on T2WI. CONCLUSIONS: The long bone hemangiomas had characteristic cystic honeycomb-like presentations in plain radiograph. CT and MRI imagings are helpful for diagnosis of hemangiomas in long bone.