Integrated analysis of muscle transcriptome, miRNA, and proteome of Chinese indigenous breed Ningxiang pig in three developmental stages.

The Ningxiang pig, a distinguished local breed in China, is recognized for its good meat quality traits. This study examines the proteomics of Ningxiang pigs at three developmental stages and delves into the upstream transcriptomics of these proteomics. Such an analysis facilitates a deeper understanding of the molecular interplay between proteins and transcriptomes in the Ningxiang pig muscle, influencing muscle growth and development. In this research, we analyzed the muscles of Ningxiang pigs at three developmental stages: 30 days in weaned piglets, 90 days in nursery pigs, and 210 days in late fattening pigs. There a total of 16 differentially co-expressed miRNAs (ssc-miRNA-1, ssc-miRNA-378, ssc-miRNA-143, ssc-miRNA-30e, etc.), 74 differentially co-expressed mRNA (PLIN3, CPT2, IGF2 and HSP90AB1, etc.) have been identified in the three stages. 572 differentially abundant proteins (DAPs) (APOC3, NDUFA2, HSPD1, ATP5E, PDHA1, etc.) were readily identified by comparing different time periods. According to the KEGG enrich pathway results that DAPs most enriched in growth and development pathways, immune mechanism pathways and maintaining functions of physical. Through short time-series expression miner (STEM) association analysis, a total of 571 negative miRNA-mRNA interaction pairs and 2 negative miRNA-mRNA-protein (Chr05_11955-Pig.17268.1-ATP5F1B, ssc-miR-194a-3p-Pig.15802.1-ACY1) interaction pairs were found. Our study provides a theoretical basis on molecular mechanism for the study of IMF deposition, muscle growth and immunity in Ningxiang pig breed.

Micromechanics and Ultrasonic Propagation in Consolidated Earthen-Site Soils.

Although nondestructive ultrasonic technologies have been applied in laboratory and field tests in the field of heritage conservation, few studies have quantified the relationship among the real microstructures, micromechanical properties, and macroscopic acoustic responses of earthen-site soils. This paper develops a micromechanics-based multiscale model for quantitatively exploring the ultrasonic propagation characteristics of elastic waves in untreated and consolidated earthen-site soils. Scanning electron microscope images and image processing technology are integrated into the finite-element simulation. The effects of microstructure and wave features on the acoustic characteristics of soils are quantitatively investigated under pulsive loading. The simulation results of untreated and consolidated soils are efficiently compared to ultrasonic test data. It is demonstrated that the integration of microstructure image processing and multiscale modeling can predict the ultrasonic pulse velocity well, which improves the accuracy of laboratory testing and field monitoring and better serves the evaluation and implementation of engineering practice in the field of heritage conservation.

Refraction correction for deep-water three-dimensional visual measurement based on multi-objective optimization.

Refraction-induced errors affect the accuracy of three-dimensional visual measurements in deepwater environments. In this study, a binocular camera refractive imaging model was established, and a calibration method for the refraction parameters was proposed for high-accuracy shape and deformation measurements in deep-water environments. First, an initial estimate of the refractive axis was obtained using a three-dimensional calibration target. Then, the errors in the distance between the spatial point pairs and the reprojection errors are taken as the dual optimization objectives, and the Non-dominated Sorting Genetic Algorithm II is applied to optimize the refraction parameters. To efficiently calculate the reprojection error, an improved numerical computation method is proposed to accelerate the calculation of the analytical forward projection. Underwater experiments were conducted to verify the method's effectiveness. The results showed that the average error of the absolute position of the reconstructed points was less than 1.1 mm and the average error of the displacement was less than 0.04 mm. This study provides a sound solution for accurate three-dimensional visual measurement in deep-water environments.

Exploring Adaptive Graph Topologies and Temporal Graph Networks for EEG-Based Depression Detection.

In recent years, Graph Neural Networks (GNNs) based on deep learning techniques have achieved promising results in EEG-based depression detection tasks but still have some limitations. Firstly, most existing GNN-based methods use pre-computed graph adjacency matrices, which ignore the differences in brain networks between individuals. Additionally, methods based on graph-structured data do not consider the temporal dependency information of brain networks. To address these issues, we propose a deep learning algorithm that explores adaptive graph topologies and temporal graph networks for EEG-based depression detection. Specifically, we designed an Adaptive Graph Topology Generation (AGTG) module that can adaptively model the real-time connectivity of the brain networks, revealing differences between individuals. In addition, we designed a Graph Convolutional Gated Recurrent Unit (GCGRU) module to capture the temporal dynamical changes of brain networks. To further explore the differential features between depressed and healthy individuals, we adopt Graph Topology-based Max-Pooling (GTMP) module to extract graph representation vectors accurately. We conduct a comparative analysis with several advanced algorithms on both public and our own datasets. The results reveal that our final model achieves the highest Area Under the Receiver Operating Characteristic Curve (AUROC) on both datasets, with values of 83% and 99%, respectively. Furthermore, we perform extensive validation experiments demonstrating our proposed method's effectiveness and advantages. Finally, we present a comprehensive discussion on the differences in brain networks between healthy and depressed individuals based on the outputs of our final model's AGTG and GTMP modules.

Distribution, Sources, and Risk Assessment of Organochlorine Pesticides in Water from Beiluo River, Loess Plateau, China.

The Loess Plateau has been a focus of public discussion and environmental concerns over the past three decades. In this study, in order to investigate the effect of OCP pollution in water of the Beiluo River, concentrations of 25 OCPs at 17 locations in the water were examined. The results showed that the concentration of ∑OCPs in the water ranged from 1.76 to 32.57 ng L-1, with an average concentration of 7.23 ng L-1. Compared with other basins in China and abroad, the OCP content in the Beiluo River was at a medium level. Hexachlorocyclohexane (HCH) pollution in the Beiluo River was mainly from the mixed input of lindane and technical HCHs. Dichlorodiphenyltrichloroethane (DDT) pollution was mainly from the mixed input of technical DDTs and dicofol. Most of the OCP pollution came from historical residues. The risk assessment results showed that hexachlorobenzene (HCB) and endosulfan had high ecological risks in the middle and lower reaches of the Beiluo River. Most residual OCPs were not sufficient to pose carcinogenic and non-carcinogenic health risks to humans. The results of this study can provide a reference for OCP prevention and control and watershed environmental management.

Single-Camera Three-Dimensional Digital Image Correlation with Enhanced Accuracy Based on Four-View Imaging.

Owing to the advantages of cost-effectiveness, compactness, and the avoidance of complicated camera synchronization, single-camera three-dimensional (3D) digital image correlation (DIC) techniques have gained increasing attention for deformation measurement of materials and structures. In the traditional single-camera 3D-DIC system, the left and right view images can be recorded by a single camera using diffraction grating, a bi-prism, or a set of planar mirrors. To further improve the measurement accuracy of single-camera 3D-DIC, this paper introduces a single-camera four-view imaging technique by installing a pyramidal prism in front of the camera. The 3D reconstruction of the measured points before and after deformation is realized with eight governing equations induced by four views, and the strong geometric constraints of four views can help to improve the measurement accuracy. A static experiment, a rigid body translation experiment, and a four-point bending experiment show that the proposed single-camera 3D-DIC method can achieve higher measurement accuracy than the dual-view single-camera 3D-DIC techniques and that the single-camera 3D-DIC method has advantages in reducing both random error and systematic error.

A look under the hood of genomic-estimated breed compositions for brangus cattle: What have we learned?

The Brangus cattle were developed to utilize the superior traits of Angus and Brahman cattle. Their genetic compositions are expected to be stabilized at 3/8 Brahman and 5/8 Angus. Previous studies have shown more than expected Angus lineage with Brangus cattle, and the reasons are yet to be investigated. In this study, we revisited the breed compositions for 3,605 Brangus cattle from three perspectives: genome-wise (GBC), per chromosomes (CBC), and per chromosome segments (SBC). The former (GBC) depicted an overall picture of the "mosaic" genome of the Brangus attributable to their ancestors, whereas the latter two criteria (CBC and SBC) corresponded to local ancestral contributions. The average GBC for the 3,605 Brangus cattle were 70.2% Angus and 29.8% Brahman. The K-means clustering supported the postulation of the mixture of 1/2 Ultrablack (UB) animals in Brangus. For the non-UB Brangus animals, the average GBC were estimated to be 67.4% Angus and 32.6% Brahman. The 95% confidence intervals of their overall GBC were 60.4%-73.5% Angus and 26.5%-39.6% Brahman. Possibly, genetic selection and drifting have resulted in an approximately 5% average deviation toward Angus lineage. The estimated ancestral contributions by chromosomes were heavily distributed toward Angus, with 27 chromosomes having an average Angus CBC greater than 62.5% but only two chromosomes (5 and 20) having Brahman CBC greater than 37.5%. The chromosomal regions with high Angus breed proportions were prevalent, tending to form larger blocks on most chromosomes. In contrast, chromosome segments with high Brahman breed proportion were relatively few and isolated, presenting only on seven chromosomes. Hence, genomic hitchhiking effects were strong where Angus favorable alleles resided but weak where Brahman favorable alleles were present. The functions of genes identified in the chromosomal regions with high ( ≥ 75 % ) Angus compositions were diverse yet may were related to growth and body development. In contrast, the genes identified in the regions with high ( ≥ 37.5 % ) Brahman compositions were primarily responsible for disease resistance. In conclusion, we have addressed the questions concerning the Brangus genetic make-ups. The results can help form a dynamic picture of the Brangus breed formation and the genomic reshaping.

Progress in Research on TLR4-Mediated Inflammatory Response Mechanisms in Brain Injury after Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is one of the common clinical neurological emergencies. Its incidence accounts for about 5-9% of cerebral stroke patients. Even surviving patients often suffer from severe adverse prognoses such as hemiplegia, aphasia, cognitive dysfunction and even death. Inflammatory response plays an important role during early nerve injury in SAH. Toll-like receptors (TLRs), pattern recognition receptors, are important components of the body's innate immune system, and they are usually activated by damage-associated molecular pattern molecules. Studies have shown that with TLR 4 as an essential member of the TLRs family, the inflammatory transduction pathway mediated by it plays a vital role in brain injury after SAH. After SAH occurrence, large amounts of blood enter the subarachnoid space. This can produce massive damage-associated molecular pattern molecules that bind to TLR4, which activates inflammatory response and causes early brain injury, thus resulting in serious adverse prognoses. In this paper, the process in research on TLR4-mediated inflammatory response mechanism in brain injury after SAH was reviewed to provide a new thought for clinical treatment.

Risk factors and predictive models of poor prognosis and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage complicated with hydrocephalus.

Objective: To evaluate the correlation of serum biological markers and related scales to the occurrence of delayed cerebral ischemia and clinical prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH) complicated with acute hydrocephalus before admission. Methods: The clinical data of 227 patients with pre-admission aSAH complicated with acute hydrocephalus admitted to Henan Provincial People's Hospital from April 2017 to December 2020 were retrospectively analyzed. Patients were grouped according to the presence or absence of delayed cerebral ischemia (DCI) after surgery and the prognosis at 6 months after discharge. Univariate and multivariable logistic regression analysis were performed to analyze the relationship between serum biological indicators combined with aneurysm related clinical score scale and the occurrence and prognosis of delayed cerebral ischemia. ROC curves and nomogram were drawn. Results: Multivariable Logistic regression analysis showed that high Hunt-Hess grade and surgical clipping were independent risk factors for postoperative DCI (P < 0.05). Older age, higher Hunt-Hess grade, higher CRP and neutrophil levels were independent risk factors for poor prognosis at 6 months after surgery (P < 0.05). ROC curve analysis showed that the area under the curve (AUC) of Hunt-Hess grade and surgical method for predicting DCI in patients with aSAH combined with hydrocephalus after surgery were 0.665 and 0.593. The combined AUC of Hunt-Hess grade and surgical method was 0.685, the sensitivity was 64.9%, and the specificity was 64.7%. The AUC of CRP, neutrophil, age and Hunt-Hess grade for predicting poor prognosis in patients with aSAH combined with hydrocephalus at 6 months after surgery were 0.804, 0.735, 0.596, 0.757, respectively. The combined AUC of CRP, neutrophil, age, Hunt-Hess grade was 0.879, the sensitivity was 79%, and the specificity was 84.5%. According to the correction curve, the predicted probability of the nomogram is basically consistent with the actual probability. Conclusion: Hunt-Hess grade and surgical method are independent predictors of postoperative DCI in patients with aSAH complicated with hydrocephalus. "CRP," "neutrophil," "age" and "Hunt-Hess grade" at admission are independent predictors of clinical prognosis in patients with aSAH complicated with hydrocephalus. The combination of the above indicators has high predictive value.

Chronic remote ischaemic conditioning in patients with symptomatic intracranial atherosclerotic stenosis (the RICA trial): a multicentre, randomised, double-blind sham-controlled trial in China.

BACKGROUND: Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide, and it is associated with a high risk of recurrent stroke with currently recommended treatments. We aimed to evaluate the effect of chronic remote ischaemic conditioning on prevention of ischaemic events in patients with symptomatic ICAS. METHODS: The RICA trial is a multicentre, randomised, double-blind, sham-controlled trial at 84 stroke centres in China. Patients aged 40-80 years with ischaemic stroke or transient ischaemic attack attributable to angiographically verified 50-99% stenosis of a major intracranial artery were randomly assigned (1:1), via an interactive web-based system by computer-generated randomisation code, to either remote ischaemic conditioning or sham remote ischaemic conditioning once daily for 12 months and voluntarily thereafter. All investigators and patients were masked to treatment allocation. The primary efficacy endpoint was the time to first occurrence of non-fatal or fatal ischaemic stroke, with survival analysed by the Kaplan-Meier method. Primary and safety analyses were done in the intention-to-treat population. The RICA trial is registered with ClinicalTrials.gov, number NCT02534545. FINDINGS: Between Oct 28, 2015, and Feb 28, 2019, 3033 patients were enrolled and randomly assigned to either remote ischaemic conditioning (n=1517; intervention group) or sham remote ischaemic conditioning (n=1516; sham group). Median follow-up was 3·5 years (IQR 2·7-4·4). A non-fatal or fatal ischaemic stroke occurred in 257 (16·9%) patients in the intervention group compared with 288 (19·0%) patients in sham group. There was no difference in the survival distribution for time to first occurrence of non-fatal or fatal ischaemic stroke (hazard ratio 0·87, 95% CI 0·74-1·03; p=0·12). In the intervention group, 79 (5·2%) patients died from any cause, and in the sham group, 84 (5·5%) patients died from any cause (hazard ratio 0·93, 95% CI 0·68-1·27; p=0·65). No intervention-related serious adverse events were observed. INTERPRETATION: No evidence was found for a difference between remote ischaemic conditioning and sham remote ischaemic conditioning in lowering the risk of ischaemic stroke in patients with symptomatic ICAS. The benefit of remote ischaemic conditioning might have been diluted by poor compliance. Future studies of remote ischaemic conditioning in this population should address challenges in patients' compliance and assess longer term treatment. FUNDING: Ministry of Science and Technology China, Beijing Municipal Education Commission, Beijing Municipal Finance Bureau. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Snapshot compressive imaging based digital image correlation: temporally super-resolved full-resolution deformation measurement.

The limited throughput of a digital image correlation (DIC) system hampers measuring deformations at both high spatial resolution and high temporal resolution. To address this dilemma, in this paper we propose to integrate snapshot compressive imaging (SCI)-a recently proposed computational imaging approach-into DIC for high-speed, high-resolution deformation measurement. Specifically, an SCI-DIC system is established to encode a sequence of fast changing speckle patterns into a snapshot and a high-accuracy speckle decompress SCI (Sp-DeSCI) algorithm is proposed for computational reconstruction of the speckle sequence. To adapt SCI reconstruction to the unique characteristics of speckle patterns, we propose three techniques under SCI reconstruction framework to secure high-precision reconstruction, including the normalized sum squared difference criterion, speckle-adaptive patch search strategy, and adaptive group aggregation. For efficacy validation of the proposed Sp-DeSCI, we conducted extensive simulated experiments and a four-point bending SCI-DIC experiment on real data. Both simulation and real experiments verify that the Sp-DeSCI successfully removes the deviations of reconstructed speckles in DeSCI and provides the highest displacement accuracy among existing algorithms. The SCI-DIC system together with the Sp-DeSCI algorithm can offer temporally super-resolved deformation measurement at full spatial resolution, and can potentially replace conventional high-speed DIC in real measurements.

Relation between Microstructures and Macroscopic Mechanical Properties of Earthen-Site Soils.

While the macroscopic mechanical properties of earthen-site soils have undergone extensive experimental and modeling studies, few research efforts focus on the relationship between the overall mechanical behavior and micro-pore structure. We developed a microstructure-based finite element model to investigate the influence of micro-pore structure on the macroscopic mechanical behavior of earthen-site soils. Scanning electron microscopy images of the untreated and consolidated soils were processed to compare the changes in equivalent diameter, sphericity, and porosity of the soils after consolidation. According to the pore parameter range of the untreated and consolidated soils, the effects of micro-pores on the soil behavior are specifically conducted under both static and dynamic loads. The relationships between pore characteristics and stiffness, strength, and ultrasonic wave velocity are established.

Assessment of biological community in riparian zone contaminated by PAHs: Linking source apportionment to biodiversity.

Riparian zone, an important land-water interface, plays an essential role in maintaining the ecological health of rivers, whereas the effects of Polycyclic aromatic hydrocarbons (PAHs) on the health of biological communities in riparian groundwater remain undetermined. To understand the responses of multiple communities to environmental variables, the distribution and ecosystem risk of 16 PAHs have been investigated in the Beiluo River, China. The distribution of multiple communities in riparian groundwater was investigated by environmental DNA metabarcoding, including 16S rRNA, 18S rRNA, and COI gene sequencing for bacteria, microbial eukaryotes (including algae, fungi, and protozoa), and metazoan, respectively, followed by correlation analysis between multiple communities and PAH contamination levels. The concentration of PAHs in the Beiluo River ranged largely from 35.32 to 728.59 ng/L. Here, the Shannon's diversity index of bacteria (Firmicutes) decreased possibly due to the occurrence of Pyrene, which mainly derives from coal and biomass combustion. Furthermore, the reduced richness of fungi (Ascomycota, Basidiomycota) and algae (Chlorophyta, Chrysophyceae) can be attributed to the presence of medium molecular weight (MMW) PAHs (Pyrene, Benz(a)anthracene, Chrysene), and low molecular weight (LMW) PAHs (Naphthalene, Fluorene, Phenanthrene). The richness and Shannon's diversity index of metazoan (Arthropoda) were promoted owing to MMW PAHs (Chrysene, Fluoranthene) generated from coal and biomass combustion and traffic emission. The ecological risk of PAHs in the groundwater environment of the Beiluo River was characterized as low to medium, where LMW and MMW PAHs posed higher risk than the high molecular weight (HMW) compounds. Overall, this study provides insights into the structures of riparian multi-biological communities altered by PAHs.

Effects of age on subcutaneous adipose tissue proteins in Chinese indigenous Ningxiang pig by TMT-labeled quantitative proteomics.

Adipose tissue not only affects meat quality and animal productivity, but also participates in inflammation and immunity. Ningxiang pig is famous for their excellent meat quality, disease resistance and tolerance of roughage. It is not yet well known how proteins in adipose tissue is dynamically regulated during the growth of Ningxiang pig. This report studies the proteomic changes in subcutaneous adipose tissue in Ningxiang pigs to gain a better understanding of the molecular mechanism of fat development during the growth period. By TMT-labeled quantitative proteomic analysis of subcutaneous adipose tissue of 9 purebred Ningxiang pigs of different ages, we identified 2533 unique proteins and 716 differentially abundant proteins (DAPs), of which more than half of the DAPs were concentrated in the 90d-210d period. Retrograde endocannabinoid signaling was only significantly enriched in DAPs of N90d vs N30d, Alcoholism and Graft-versus-host disease were only significantly enriched in DAPs of N210d vs N90d. Proteins related to dilated cardiomyopathy was found to be an important pathway in fat development and lipid metabolism. A variety of novel DAPs involved in maintaining mitochondrial function and cell viability, such as NDUFS6, SDHB, COX5A, ATP5D and TNNT1, which play a role in controlling the prediction networks, may indirectly regulate the development and functional maintenance of adipocytes. SIGNIFICANCE: These age-dependent DAPs discovered in this study may help expand the understanding of the molecular mechanisms of the development, function maintenance and transformation of adipose tissue in Ningxiang pig for developing new strategies for improving meat quality and pig breeding in the future.

Spatiotemporal Regulation of Circular RNA Expression during Liver Development of Chinese Indigenous Ningxiang Pigs.

BACKGROUND: There have been many studies on the relationship between circRNAs and fat deposition. Although the liver is a central organ for fat metabolism, there are few reports on the relationship between circRNAs in the liver and fat deposition. METHODS: In this study, we systematically analyzed circular RNAs in the liver of Ningxiang pigs, at four time points after birth (30 days, 90 days, 150 days and 210 days). RESULTS: A total of 3705 circRNAs were coexpressed in four time periods were found, and KEGG analysis showed that the significantly upregulated pathways were mainly enriched in lipid metabolism and amino acid metabolism, while significantly downregulated pathways were mainly related to signal transduction, such as ECM-receptor interaction, MAPK signaling pathway, etc. Short time-series expression miner (STEM) analysis showed multiple model spectra that were significantly enriched over time in the liver. By constructing a competing endogenous RNA (ceRNA) regulatory network, 9187 pairs of networks related to the change in development time were screened. CONCLUSIONS: The expression profiles of circRNAs in Ningxiang pig liver were revealed at different development periods, and it was determined that there is differential coexpression. Through enrichment analysis of these circRNAs, it was revealed that host genes were involved in metabolism-related signaling pathways and fatty acid anabolism. Through STEM analysis, many circRNAs involved in fat metabolism, transport, and deposition pathways were screened, and the first circRNA-miRNA-mRNA regulation network map in Ningxiang pig liver was constructed. The highly expressed circRNAs related to fat deposition were verified and were consistent with RNA-Seq results.

Evaluation of Wearable Sensor Devices in Parkinson's Disease: A Review of Current Status and Future Prospects.

Parkinson's disease (PD) decreases the quality of life of the affected individuals. The incidence of PD is expected to increase given the growing aging population. Motor symptoms associated with PD render the patients unable to self-care and function properly. Given that several drugs have been developed to control motor symptoms, highly sensitive scales for clinical evaluation of drug efficacy are needed. Among such scales, the objective and continuous evaluation of wearable devices is increasingly utilized by clinicians and patients. Several electronic technologies have revolutionized the clinical monitoring of PD development, especially its motor symptoms. Here, we review and discuss the recent advances in the development of wearable devices for bradykinesia, tremor, gait, and myotonia. Our aim is to capture the experiences of patients and clinicians, as well as expand our understanding on the application of wearable technology. In so-doing, we lay the foundation for further research into the use of wearable technology in the management of PD.

Predicting seizure freedom with AED treatment in newly diagnosed patients with MRI-negative epilepsy: A large cohort and multicenter study.

OBJECTIVE: We developed and validated a prediction score for predicting the probability of 6-month and 12-month seizure freedom of antiepileptic drug (AED) treatment in newly diagnosed patients with magnetic resonance imaging (MRI)-negative epilepsy. METHODS: The development cohort included 543 consecutive patients from the Epilepsy Center of Henan Provincial People's Hospital, while the validation cohorts included 493 consecutive patients in two independent cohorts. Univariate analysis and a forward and backward elimination of multivariate Cox regression analysis were used to select predictive factors. The performance of the score was evaluated with C-index, calibration plots, and decision curve analysis. The risk stratification was also performed. RESULTS: The score included five routinely available predictors including Circadian rhythms, Electroencephalography before AED treatment, Neuropsychiatric disorders, Perinatal brain injury, and History of central nervous system infection (CENPH score). When applied to the external validation cohort, the score showed good discrimination with C-index (development group: 0.83; validation group: 0.78), and calibration plots indicated well calibration, as well as the decision curve analysis showed good predictive accuracy and clinical values in four cohorts. The points of the score were categorized to the following three probability levels for predicting seizure freedom: high probability (0-83.11 points), medium probability (83.11-122.71 points), and low probability (>122.71 points). And online calculator was established to make this score easily applicable in clinical practice. CONCLUSIONS: We established a simple, practical, and evidence-based prediction score for predicting seizure freedom with AEDs to aid in the clinical consultation and treatment decision for the newly diagnosed patients with MRI-negative epilepsy.

Distinct molecular subtypes of uterine leiomyosarcoma respond differently to chemotherapy treatment.

BACKGROUND: Uterine leiomyosarcoma (ULMS) is an aggressive form of soft tissue tumors. The molecular heterogeneity and pathogenesis of ULMS are not well understood. METHODS: Expression profiling data were used to determine the possibility and optimal number of ULMS molecular subtypes. Next, clinicopathological characters and molecular pathways were analyzed in each subtype to prospect the clinical applications and progression mechanisms of ULMS. RESULTS: Two distinct molecular subtypes of ULMS were defined based on different gene expression signatures. Subtype I ULMS recapitulated low-grade ULMS, the gene expression pattern of which resembled normal smooth muscle cells, characterized by overexpression of smooth muscle function genes such as LMOD1, SLMAP, MYLK, MYH11. In contrast, subtype II ULMS recapitulated high-grade ULMS with higher tumor weight and invasion rate, and was characterized by overexpression of genes involved in the pathway of epithelial to mesenchymal transition and tumorigenesis, such as CDK6, MAPK13 and HOXA1. CONCLUSIONS: We identified two distinct molecular subtypes of ULMS responding differently to chemotherapy treatment. Our findings provide a better understanding of ULMS intrinsic molecular subtypes, and will potentially facilitate the development of subtype-specific diagnosis biomarkers and therapy strategies for these tumors.

Cerebroprotection by the neuronal PGE2 receptor EP2 after intracerebral hemorrhage in middle-aged mice.

Inflammatory responses mediated by prostaglandins such as PGE2 may contribute to secondary brain injury after intracerebral hemorrhage (ICH). However, the cell-specific signaling by PGE2 receptor EP2 differs depending on whether the neuropathic insult is acute or chronic. Using genetic and pharmacologic approaches, we investigated the role of EP2 receptor in two mouse models of ICH induced by intrastriatal injection of collagenase or autologous arterial whole blood. We used middle-aged male mice to enhance the clinical relevance of the study. EP2 receptor was expressed in neurons but not in astrocytes or microglia after collagenase-induced ICH. Brain injury after collagenase-induced ICH was associated with enhanced cellular and molecular inflammatory responses, oxidative stress, and matrix metalloproteinase (MMP)-2/9 activity. EP2 receptor deletion exacerbated brain injury, brain swelling/edema, neuronal death, and neurobehavioral deficits, whereas EP2 receptor activation by the highly selective agonist AE1-259-01 reversed these outcomes. EP2 receptor deletion also exacerbated brain edema and neurologic deficits in the blood ICH model. These findings support the premise that neuronal EP2 receptor activation by PGE2 protects brain against ICH injury in middle-aged mice through its anti-inflammatory and anti-oxidant effects and anti-MMP-2/9 activity. PGE2/EP2 signaling warrants further investigation for potential use in ICH treatment.