Trichothecenes with cytotoxic activity and benzene derivatives with hypolipidemic activity from trichothecium sp.

Five trichothecenes including a new one, together with two previously undescribed benzene derivatives were isolated from the solid culture of Trichothecium sp. Their structures were established by 1D and 2D NMR data in conjunction with HR-ESI-MS analysis. Compounds 1-5 exhibited cytotoxicity against MCF-7 cell lines at various levels ranging from IC50 of 7.23 to 16.95 µM. Compound 6 decreased the concentration of blood lipids in zebra fish at the concentration of 20 µM.

lncRNA Hnscr Regulates Lipid Metabolism by Mediating Adipocyte Lipolysis.

Obesity is a process of fat accumulation due to the imbalance between energy intake and consumption. Long noncoding RNA (lncRNA) Hnscr is crucial for metabolic regulation, but its roles in lipid metabolism during obesity are still unknown. In this article, we found that the expression of Hnscr gradually decreased in adipose tissues of diet-induced obese mice. Furthermore, the deletion of Hnscr promoted an increase in body weight and adipose tissue weight by upregulating the expression of lipogenesis genes and downregulating lipolysis genes in inguinal white adipose tissue (iWAT) and brown adipose tissue. In vitro knockdown of Hnscr in adipocytes resulted in reduced lipolysis of adipocytes. Overexpression of Hnscr by adenovirus or drug mimics showed the opposite. Mechanistically, Hnscr regulated adipose lipid metabolism by mediating the cyclic adenosine monophosphate/protein kinase A signaling pathway. This study identifies the initial characterization of Hnscr as a critical modifier that regulates lipid metabolism, suggesting that lncRNA Hnscr is a potential target for treating obesity.

Value of Radiomic Analysis Combined With Diffusion Tensor Imaging in Early Diagnosis of HIV-Associated Neurocognitive Disorders.

BACKGROUND: The combination of radiomics and diffusion tensor imaging (DTI) may have potential clinical value in the early stage of HIV-associated neurocognitive disorders (HAND). PURPOSE: To investigate the value of DTI-based radiomics in the early stage of HAND in people living with HIV (PLWH). STUDY TYPE: Retrospective. POPULATION: A total of 138 male PLWH were included, including 68 with intact cognition (IC) and 70 with asymptomatic neurocognitive impairment (ANI). Seventy healthy controls (HCs) were recruited for tract-based spatial statistics (TBSS) analysis. All PLWHs were randomly divided into training and validation cohorts at a 7:3 ratio. FIELD STRENGTH/SEQUENCE: A 3 T, single-shot spin-echo echo planar imaging (EPI). ASSESSMENT: The differences between the PLWH groups were compared using TBSS and region of interest (ROI) analysis. Radiomic features were extracted from the corpus callosum (CC) on DTI postprocessed images, including fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD). The performance of the radiomic signatures was evaluated by ROC curve analysis. The radiomic signature with the highest area under the curve (AUC) was combined with clinical characteristics to construct a nomogram. Decision curve analysis (DCA) was performed to evaluate the ability of different methods in discriminating ANI. STATISTICAL TESTS: Chi-square test, independent-samples t test, Kruskal-Wallis test, Mann-Whitney U test, threshold-free cluster enhancement (TFCE), ROC curve analysis, DCA, multivariate logistic regression analysis, Hosmer-Lemeshow test. P < 0.05 with TFCE corrected and P < 0.0001 without TFCE corrected were considered statistically significant. RESULTS: The ANI group showed lower FA and higher AD than the IC group. In the validation cohort, the AUCs of the FA-, AD-, MD- and RD-based radiomic signatures and the clinicoradiomic nomogram were 0.829, 0.779, 0.790, 0.864, and 0.874, respectively. DCA revealed that the nomogram was of greater clinical value than TBSS analysis, the clinical models, and the RD-based radiomic signature. DATA CONCLUSION: The combination of DTI and radiomics is correlated with early stage of HAND in PLWH. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

RSU-Net: U-net based on residual and self-attention mechanism in the segmentation of cardiac magnetic resonance images.

BACKGROUND: Automated segmentation techniques for cardiac magnetic resonance imaging (MRI) are beneficial for evaluating cardiac functional parameters in clinical diagnosis. However, due to the characteristics of unclear image boundaries and anisotropic resolution anisotropy produced by cardiac magnetic resonance imaging technology, most of the existing methods still have the problems of intra-class uncertainty and inter-class uncertainty. However, due to the irregularity of the anatomical shape of the heart and the inhomogeneity of tissue density, the boundaries of its anatomical structures become uncertain and discontinuous. Therefore, fast and accurate segmentation of cardiac tissue remains a challenging problem in medical image processing. METHODOLOGY: We collected cardiac MRI data from 195 patients as training set and 35patients from different medical centers as external validation set. Our research proposed a U-net network architecture with residual connections and a self-attentive mechanism (Residual Self-Attention U-net, RSU-Net). The network relies on the classic U-net network, adopts the U-shaped symmetric architecture of the encoding and decoding mode, improves the convolution module in the network, introduces skip connections, and improves the network's capacity for feature extraction. Then for solving locality defects of ordinary convolutional networks. To achieve a global receptive field, a self-attention mechanism is introduced at the bottom of the model. The loss function employs a combination of Cross Entropy Loss and Dice Loss to jointly guide network training, resulting in more stable network training. RESULTS: In our study, we employ the Hausdorff distance (HD) and the Dice similarity coefficient (DSC) as metrics for assessing segmentation outcomes. Comparsion was made with the segmentation frameworks of other papers, and the comparison results prove that our RSU-Net network performs better and can make accurate segmentation of the heart. New ideas for scientific research. CONCLUSION: Our proposed RSU-Net network combines the advantages of residual connections and self-attention. This paper uses the residual links to facilitate the training of the network. In this paper, a self-attention mechanism is introduced, and a bottom self-attention block (BSA Block) is used to aggregate global information. Self-attention aggregates global information, and has achieved good segmentation results on the cardiac segmentation dataset. It facilitates the diagnosis of cardiovascular patients in the future.

Hypothalamic Hnscr regulates glucose balance by mediating central inflammation and insulin signal.

OBJECTIVES: Hypothalamic dysfunction leads to glucose metabolic imbalance; however, the mechanisms still need clarification. Our current study was to explore the role of hypothalamic Hnscr in glucose metabolism. MATERIALS AND METHODS: Using Hnscr knockout or htNSC-specific Hnscr overexpression mice, we evaluated the effects of Hnscr on glucose metabolism through GTTs, ITTs, serum indicator measurements, etc. Immunofluorescence staining and Western blotting were performed to test inflammation levels and insulin signalling in hypothalamus. Conditioned medium intervene were used to investigate the effects of htNSCs on neuronal cell line. We also detected the glucose metabolism of mice with htNSCs implantation. RESULTS: Hnscr expression decreased in the hypothalamus after high-fat diet feed. Hnscr-null mice displayed aggravated systematic insulin resistance, while mice with htNSC-specific Hnscr overexpression had the opposite phenotype. Notably, Hnscr-null mice had increased NF-κB signal in htNSCs, along with enhanced inflammation and damaged insulin signal in neurons located in arcuate nucleus of hypothalamus. The secretions, including sEVs, of Hnscr-deficient htNSCs mediated the detrimental effects on the CNS cell line. Locally implantation with Hnscr-depleted htNSCs disrupted glucose homeostasis. CONCLUSIONS: This study demonstrated that decreased Hnscr in htNSCs led to systematic glucose imbalance through activating NF-κB signal and dampening insulin signal in hypothalamic neurons.

Cardiac MRI segmentation of the atria based on UU-NET.

Background and objective: In today's society, people's work pressure, coupled with irregular diet, lack of exercise and other bad lifestyle, resulting in frequent cardiovascular diseases. Medical imaging has made great progress in modern society, among which the role of MRI in cardiovascular field is self-evident. Based on this research background, how to process cardiac MRI quickly and accurately by computer has been extensively discussed. By comparing and analyzing several traditional image segmentation and deep learning image segmentation, this paper proposes the left and right atria segmentation algorithm of cardiac MRI based on UU-NET network. Methods: In this paper, an atrial segmentation algorithm for cardiac MRI images in UU-NET network is proposed. Firstly, U-shaped upper and lower sampling modules are constructed by using residual theory, which are used as encoders and decoders of the model. Then, the modules are interconnected to form multiple paths from input to output to increase the information transmission capacity of the model. Results: The segmentation method based on UU-NET network has achieved good results proposed in this paper, compared with the current mainstream image segmentation algorithm results have been improved to a certain extent. Through the analysis of the experimental results, the image segmentation algorithm based on UU-NET network on the data set, its performance in the verification set and online set is higher than other grid models. The DSC in the verification set is 96.7%, and the DSC in the online set is 96.7%, which is nearly one percentage point higher than the deconvolution neural network model. The hausdorff distance (HD) is 1.2 mm. Compared with other deep learning models, it is significantly improved (about 3 mm error is reduced), and the time is 0.4 min. Conclusion: The segmentation algorithm based on UU-NET improves the segmentation accuracy obviously compared with other segmentation models. Our technique will be able to help diagnose and treat cardiac complications.

Pro-Resolving Mediator Resolvin E1 Restores Alveolar Fluid Clearance in Acute Respiratory Distress Syndrome.

ABSTRACT: Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by increased permeability of the alveolar-capillary barrier and impaired alveolar fluid clearance. Resolvin E1 (RvE1) is a specialized pro-resolving mediator derived endogenously from omega-3-polyunsaturated fatty acids. RvE1 (10 µg/kg i.v.) was injected to rats 6 h post-lipopolysaccharide (LPS) (14 mg/kg) induction. After another 3 h, alveolar fluid clearance was measured in live rats (n = 8-9). The primary Type II alveolar epithelial cell was isolated and treated by LPS (1 µg/mL) with or without RvE1 (250 nM). The expression of epithelial sodium channel (ENaC), Na+/K+-ATPase (NKA), AKT, serum- and glucocorticoid-induced kinase 1 (SGK1), and Nedd4-2 were detected. RvE1 improved survival rate (30% vs. 70%, P = 0.048), increased the clearance of alveolar fluid (13.34% vs. 18.73%, P  < 0.001), reduced lung wet-dry weight ratio (5.01 vs. 4.63, P  < 0.001), mitigated lung injury scores (13.38 vs. 7.0, P  < 0.05) and inflammation in LPS-induced ARDS in rats. RvE1 upregulated alveolar ENaC and NKA expression in vivo and in vitro. In addition, RvE1 significantly increased the expression of phosphorylated AKT, SGK1, and phosphorylated Nedd4-2 in LPS-stimulated primary alveolar type II cells. The effects of RvE1 were abrogated by blocking phosphatidylinositide3'-kinase (PI3K) and SGK1 with LY294002 and GSK650394, respectively. In summary, RvE1 upregulated ENaC and NKA expression by activating PI3K/AKT/SGK1 pathway to promote alveolar fluid clearance, suggesting that RvE1 may be a potentially effective drug for ARDS treatment.

Proangiogenic functions of osteopontin-derived synthetic peptide RSKSKKFRR in endothelial cells and postischemic brain.

OBJECTIVE: The aim of this study was to investigate the potential therapeutic effects of a newly discovered osteopontin-derived synthetic peptide "RSKKFRR" in a rat model of ischemic stroke. METHODS: A total of 24 male SD rats were randomly divided into three groups. The model of ischemic stroke was made up of the middle cerebral artery occlusion (MACO). The rats were divided into sham operation group (Sham), control group (MACO + PBS) and treatment group (MACO + OPNpt9), eight rats in each group. In the control group and the treatment group, PBS or OPNpt9 was injected into the nasal cavity after MACO once a day, and the area of new blood vessels and the recovery of nerve function were observed 14 days later. Whether the proliferation, migration and tube formation of HUVECs were promoted by OPNpt9 was tested. The expression levels of related proangiogenic factors were also detected. RESULTS: OPNpt9 was found to contribute to cerebral microvascular remodeling and neurological improvement in ischemic rats while promoting endothelial cell migration, proliferation and tube formation in vitro. These effects were mediated by activation of the p-ERK/MMP-9/VEGF pathway. CONCLUSION: In conclusion, OPNpt9 promotes angiogenesis and neurological recovery after ischemic stroke.

The role of autophagy in bone homeostasis.

Autophagy is an evolutionarily conserved intracellular process and is considered one of the main catabolism pathways. In the process of autophagy, cells are digested nonselectively or selectively to recover nutrients and energy, so it is regarded as an antiaging process. In addition to the essential role of autophagy in cellular homeostasis, autophagy is a stress response mechanism for cell survival. Here, we review recent literature describing the pathway of autophagy and its role in different bone cell types, including osteoblasts, osteoclasts, and osteocytes. Also discussed is the mechanism of autophagy in bone diseases associated with bone homeostasis, including osteoporosis and Paget's disease. Finally, we discuss the application of autophagy regulators in bone diseases. This review aims to introduce autophagy, summarize the understanding of its relevance in bone physiology, and discuss its role and therapeutic potential in the pathogenesis of bone diseases such as osteoporosis.

Characteristics of Brain White Matter Microstructure in HIV Male Patients With Primary Syphilis Co-Infection.

Purpose: To investigate the effect of syphilis infection on the microstructure of white matter (WM) in HIV-infected male patients using diffusion tensor imaging (DTI). Methods: Twenty-seven HIV-infected male patients with current syphilis or a history of syphilis (HIV +/syphilis +), twenty-nine HIV-infected male patients without syphilis co-infection (HIV +/syphilis-), and twenty-nine healthy controls (HC) were enrolled. All participants received DTI, and all patients received comprehensive neuropsychological assessment. Tract-based spatial statistics (TBSS) was adopted to analyze the DTI measures: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Correlation analysis was conducted to investigate the relationships between DTI measures and cognitive performance. Results: There were no significant differences in DTI measures between HIV+/syphilis- and HC. Compared with HC, lower FA was found in body of corpus callosum (BCC), splenium of corpus callosum (SCC), genu of corpus callosum (GCC), the bilateral anterior corona radiata (ACR), superior corona radiata (SCR), posterior corona radiata (PCR), and posterior thalamic radiation (PTR) in HIV+/syphilis+ (p < 0.05). Higher RD was found in BCC and SCC (p < 0.05). Compared with HIV+/syphilis-, lower scores were found in complex motor skills (CMS) in HIV+/syphilis+, lower FA was found in BCC, SCC, GCC, the bilateral ACR, SCR, PCR, PTR, cingulate gyrus (CGC), the right inferior fronto-occipital fasciculus (IFO), the retrolenticular part of internal capsule (RLIC), sagittal stratum (SS), external capsule (EC) in HIV+/syphilis+ (p < 0.01). Correlation analysis uncorrected for multiple comparisons showed there was a positive correlation between FA in GCC and CMS, FA in BCC, and CMS in HIV+/syphilis+. Conclusions: Syphilis co-infection can have an additive or synergistic effect on the brain WM in HIV-infected subjects. HIV-infected patients without syphilis should be actively treated to avoid syphilis infection.

[Study of human papillomavirus in small cell neuroendocrine carcinoma of the uterine cervix].

OBJECTIVE: To observe the infection of the high risk human papillomavirus (HPV) in the specimen of the small cell neuroendocrine carcinoma of the uterine cervix (SCNEC). METHODS: We extracted the nucleic acids in the formalin-fixed and paraffin-embedded specimen from a 33-year-old patient diagnosed as small cell neuroendocrine carcinoma of uterine cervix and detected the HPV genotype with the nested PCR. RESULTS: We identified HPV18, a high-risk genotype, in the specimen. CONCLUSION: The HPV detection with the nested PCR was available for identification of the HPV genotype(s) in the paraffin-embedded specimens of small cell neuroendocrine carcinoma of the uterine cervix with a high accuracy and sensitivity.

[Human papillomavirus detection in clear cell carcinoma of the cervix].

OBJECTIVE: To investigate the infection of the high risk human papillomavirus (HPV) in the specimen of the clear cell carcinoma of the cervix. METHODS: We extracted the nucleic acids in the formalin-fixed and paraffin-embedded specimens from a 37-year-old patient with clear cell carcinoma of the cervix and detected the HPV genotype with the nested PCR. RESULTS: We identified HPV18, a high-risk genotype, in the specimens. CONCLUSION: The HPV detection with the nested PCR was available for identification of the HPV genotype(s) in the paraffin-embedded specimens of clear cell carcinoma of the cervix (CCCC) with a high accuracy and sensitivity.