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关键词： RNA-SILENCING COMPLEX   CRYSTAL-STRUCTURE   EVOLUTIONARY CLASSIFICATION   CMR2-CMR3 SUBCOMPLEX   DNA CLEAVAGE   IMMUNITY   MECHANISM   PROTEIN   SUBUNIT   CSX1  

摘要： CRISPR loci and CRISPR-associated (Cas) genes encode an adaptive immune system that protects many bacterial and almost all archaea against invasive genetic elements from bacteriophages and plasmids. Several classes of CRISPR systems have been characterized, of which the type III CRISPR systems exhibit the most unique functions. Members of type III cleave both RNA and DNA not only through their corresponding effector complexes but also by CRISPR-Cas associated proteins activated by second messengers produced by those effector complexes. Furthermore, the recent discovery of second messenger degrading proteins called ring nucleases adds an extra regulatory layer to fine-tune these immunity systems. Here, we review the defense mechanisms that govern type III CRISPR interference immunity systems focusing on the structural information available.

关键词： Skeletal muscle cells   Energy metabolism   Age   Body mass index (BMI)   Muscle of origin   Gender   FATTY-ACID-METABOLISM   REDUCED LIPID OXIDATION   MITOCHONDRIAL-FUNCTION   GLUCOSE-METABOLISM   INSULIN-RESISTANCE   FIBER TYPES   OBESITY   EXERCISE   ACCUMULATION   MYOTUBES  

摘要： Primary human myotubes represent an alternative system to intact skeletal muscle for the study of human diseases related to changes in muscle energy metabolism. This work aimed to study if fatty acid and glucose metabolism in human myotubes in vitro were related to muscle of origin, donor gender, age, or body mass index (BMI). Myotubes from a total of 82 donors were established from three different skeletal muscles, i.e.,musculus vastus lateralis,musculus obliquus internus abdominis, andmusculi interspinales, and cellular energy metabolism was evaluated. Multiple linear regression analyses showed that donor age had a significant effect on glucose and oleic acid oxidation after correcting for gender, BMI, and muscle of origin. Donor BMI was the only significant contributor to cellular oleic acid uptake, whereas cellular glucose uptake did not rely on any of the variables examined. Despite the effect of age on substrate oxidation, cellular mRNA expression of pyruvate dehydrogenase kinase 4 (PDK4) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) did not correlate with donor age. In conclusion, donor age significantly impacts substrate oxidation in cultured human myotubes, whereas donor BMI affects cellular oleic acid uptake.

关键词： Biological soil crusts   Polysaccharides   Primary cell wall   Succession   Development   Photosynthetic organisms   SUCCESSIONAL STAGES   MICROCOLEUS-VAGINATUS   ENVIRONMENTAL-FACTORS   ENZYME-ACTIVITIES   COLORADO PLATEAU   ALGAL CRUSTS   CYANOBACTERIAL   DYNAMICS   EXOPOLYSACCHARIDES   COMMUNITIES  

摘要： The relative abundances of microbial community, chlorophyll content, and exopolysaccharides are used as indices in assessing the developmental level of biological soil crusts (BSCs). However, the macromolecular polysaccharide of primary cell wall (PCW) is rarely mentioned. In this study, the monosaccharide composition of PCW polysaccharides were used to assess the developmental level of BSCs with accurate crusted ages on a large time scale (9-61 years), and chlorophyll contents, total carbohydrates, moss abundances, and cyanobacterial abundances were investigated. Relative moss abundances were significantly and positively correlated with the increase in crusted age; chlorophyll content; and the percentage of monosaccharides, such as mannose, arabinose, and galactose, in PCW polysaccharides. Relative cyanobacterial abundances were significantly correlated with monosaccharides, such as fucose, glucose, and ribose. These results suggested that the monosaccharide percentage of PCW polysaccharides could be a good developmental level indicator for assessing the developmental level and succession phage of BSCs.

摘要： Introduction Mast cells play critical roles in cancer pathway. We aimed to prospectively investigate the urinary mast cell activation markers in patients with non-muscle invasive bladder cancer (NMIBC) treated with Bacillus Calmette-Guérin (BCG). Methods Nineteen patients who were received immunotherapy due to NMIBC and 19 healthy participants were enrolled. Urine samples were collected to assay N-methylhistamine, histamine and tryptase levels immediately before the first BCG instillation, immediately after the third and sixth instillations, and four weeks after the sixth instillation in patients with NMIBC and at a single visit in healthy participants. Cystoscopy were performed on the patient with NMIBC at three-month intervals for two years. The changes in urinary markers due to BCC response, BCG instillation, and presence of NMIBC were assessed. Results The average age was 56.1 ± 10.5 years. Fourteen patients had high-grade Ta tumors, and 5 had high-grade T1 tumors. While 12 patients responded, 6 presented with recurrence and 1 with progression. There was no correlation between mast cell activation markers and BCG response. The N-methylhistamine and histamine levels were increased significantly with the onset of immunotherapy and N-methylhistamine levels were decreased significantly when immunotherapy was terminated. Pre-BCG estimated marginal means of N-methylhistamine were significantly higher in patients with NMIBC than healthy participants. Conclusions This is the first study to determine that urine N-methylhistamine levels increase with BCG instillation and NMIBC presence. However, urinary mast cell activation markers were not found to significantly predict the patients’ response to immunotherapy. Further studies are required to ascertain the clinical implications of these finding.

关键词： germ cell tumor   cystic trophoblastic tumor   choriocarcinoma   yolk sac tumor  

摘要： Cystic trophoblastic tumor (CTT) is an uncommon trophoblastic proliferation of germ cell tumor origin, mostly reported in post-chemotherapy metastases of testicular germ cell tumors and rarely primary untreated testicular tumors. To date, we are not aware of occurrence in a non-testicular tumor. A 12-year-old boy presented with limb swelling, increased appetite, weight gain, and precocious puberty. Evaluation revealed right frontal lobe mass and elevated alpha-fetoprotein and beta-human chorionic gonadotrophin. After response to neoadjuvant chemotherapy, the tumor was resected. Microscopically, the resection contained predominantly smooth muscle tissue with scattered small foci of glandular teratoma and CTT. Immunohistochemistry (SALL4, glypican 3) revealed no residual yolk sac tumor. Fluorescence in situ hybridization revealed gain of chromosome 12p. The patient has been disease-free for 13 years. This report expands the spectrum of primary central nervous system germ cell tumors with the occurrence of CTT in this site.

关键词： Rewards   fMRI   Meta-analyses   Striatum   Basal ganglia   DORSOLATERAL PREFRONTAL CORTEX   HUMAN ORBITOFRONTAL CORTEX   ALTERED NEURAL RESPONSE   VISUAL EROTIC STIMULI   BRAIN ACTIVATION   DECISION-MAKING   MONETARY REWARD   SEXUAL AROUSAL   NUCLEUS-ACCUMBENS   FUNCTIONAL CONNECTIVITY  

摘要： Reward processing is a fundamental human activity. The basal ganglia are recognized for their role in reward processes; however, specific roles of the different nuclei (e.g., nucleus accumbens, caudate, putamen and globus pallidus) remain unclear. Using quantitative meta-analyses we assessed whole-brain and basal ganglia specific contributions to money, erotic, and food reward processing. We analyzed data from 190 fMRI studies which reported stereotaxic coordinates of whole-brain, within-group results from healthy adult participants. Results showed concordance in overlapping and distinct cortical and sub-cortical brain regions as a function of reward type. Common to all reward types was concordance in basal ganglia nuclei, with distinct differences in hemispheric dominance and spatial extent in response to the different reward types. Food reward processing favored the right hemisphere; erotic rewards favored the right lateral globus pallidus and left caudate body. Money rewards engaged the basal ganglia bilaterally including its most anterior part, nucleus accumbens. We conclude by proposing a model of common reward processing in the basal ganglia and separate models for money, erotic, and food rewards.

关键词： Buffalo   Curcumin   Endometritis   In vitro   LTA   LPS   NF-KAPPA-B   STAPHYLOCOCCUS-AUREUS   EPITHELIAL-CELLS   UP-REGULATION   INTERLEUKIN-8   TRANSCRIPTS   CYTOLOGY   PATHWAY   HEALTH   CYCLE  

摘要： Infection of the uterus with Gram-positive Trueperella pyogenes and Gram-negative Escherichia coli is a common cause of postpartum endometritis in the cattle and buffalo and the condition is treated with antimicrobial drugs. The presence of drug residues in the milk and development of resistant bacteria necessitate the evaluation of alternate therapies for endometritis. Accordingly, we tested the immunomodulatory effect of curcumin in the bubaline endometrial stromal cells after treatment with the lipoteichoic acid (LTA) of Gram-positive Staphylococcus aureus and lipopolysaccharide (LPS) of Gram-negative E. coli that activate toll-like receptors (TLR-2 and TLR-4, respectively). Confluent primary culture of endometrial stromal cells was treated with LTA (1 mu g/mL) and/or LPS (0.1 mu g/mL), in the presence or absence of curcumin (30 mu M for 24 h). PGE(2) was assayed in the supernatant and the relative expression of proinflammatory cytokines (PICs) (IL1B, IL6, IL8 and TNFA) transcripts were quantified using real-time PCR. LTA was not effective in stimulating PGE(2) production or upregulating the PIC expression except IL8. LTA+LPS increased PGE(2) production and upregulated IL6 and IL8 genes. Curcumin inhibited the basal and LTA+LPS induced production of PGE(2) and upregulation of PIC production. It was apparent that LPS, but not LTA, is a potent stimulator of PGE(2) from the bubaline endometrial stromal cells. Curcumin downregulated the expression of LPS and/or LTA induced PICs and PGE(2) and may be an alternate to antimicrobial drugs for the therapeutic management of endometritis.

关键词： Total lesion glycolysis   National Comprehensive Cancer Network International Prognostic Index   Cell of origin   Survival   Primary intestinal DLBCL   Prognosis   METABOLIC TUMOR VOLUME   NON-HODGKINS-LYMPHOMA   STAGING F-18-FDG PET/CT   CLINICAL-FEATURES   PARAMETERS   SURVIVAL   INDEX   PREDICTOR   CLASSIFICATION   CHEMOTHERAPY  

摘要： Purpose The prognostic value of(18)F-FDG PET/CT for primary intestinal diffuse large B-cell lymphoma (PI-DLBCL) patients has not been determined. This prompted us to explore the value of(18)F-FDG PET/CT for prognostic stratification in patients with PI-DLBCL treated with an R-CHOP-like regimen. Materials and methods Seventy-three PI-DLBCL patients who underwent baseline PET/CT between January 2010 and May 2019 were included in this retrospective study. Total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) were computed using the 41% SUV(max)thresholding method. Progression-free survival (PFS) and overall survival (OS) were used as endpoints to evaluate prognosis. Results During the follow-up period of 3-117 months (29.0 +/- 25.5 months), high TLG, non-germinal center B-cell-like (non-GCB) and high National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) were significantly associated with inferior PFS and OS. TLG, cell-of-origin and NCCN-IPI were independent predictors of PFS, and both TLG and NCCN-IPI were independent predictors of OS. The grading system was based on the number of risk factors (high TLG, non-GCB, high NCCN-IPI) and patients were divided into 4 risk groups (PFS:chi(2) = 33.858,P < 0.001; OS:chi(2) = 29.435,P < 0.001): low-risk group (none of the 3 risk factors, 18 patients); low-intermediate risk group (1 risk factor, 24 patients); high-intermediate risk group (2 risk factors, 16 patients); and high-risk group (all 3 risk factors, 15 patients). Conclusions High TLG, non-GCB and high NCCN-IPI can identify a subset of PI-DLBCL patients with inferior survival outcomes. Furthermore, the grading system can identify PI-DLBCL patient groups with markedly different prognoses, which might contribute to the adjustment of the therapeutic regime.

关键词： Rhabdomyosarcoma   Muscle cells   Calcium ions   Electroporation   Caspase 3   Apoptosis   POLY(ADP-RIBOSE) POLYMERASE-1   SKIN PERMEATION   STIMULATION   ACTIVATION   MECHANISMS   EXPRESSION   INDUCTION   CASPASES   CHLORIDE  

摘要： Calcium electroporation (CaEP) has been previously reported as an effective method of rhabdomyosarcoma cells reduction. CaEP causes temporary cell membrane permeabilization with simultaneous calcium ions influx. A rapid influx of calcium ions leads to mitochondrial overload by Ca2+, loss of mitochondrial membrane potential causing cytochrome c release, caspase cascade activation and, as a consequence, cell death. This study was conducted on two cell lines: normal muscle cells (C2C12) and rhabdomyosarcoma cells (RD), which showed different cellular responses to CaEP. Our study defined apoptosis as the main cell death type occurring after CaEP in RD cells. Increased activity of caspase 3/7, Parp-1 and cleaved Parp-1 were proven in the case of RD cells. RD cells compartment rearrangement was observed in the time-lapse by holotomographic microscopy (HTM). C2C12 cells were less sensitive to electroporation and increased Ca2+ concentration, and viability was maintained at the level of control cells, only slight changes in pro-apoptotic factors were observed. The results reveal CaEP as a promising therapeutic approach in cancers which develop from muscle tissue. (C) 2020 Elsevier B.V. All rights reserved.