Calmodulin Triggers Activity-Dependent rRNA Biogenesis via Interaction with DDX21.

Protein synthesis in response to neuronal activity, known as activity-dependent translation, is critical for synaptic plasticity and memory formation. However, the signaling cascades that couple neuronal activity to the translational events remain elusive. In this study, we identified the role of calmodulin (CaM), a conserved Ca2+-binding protein, in ribosomal RNA (rRNA) biogenesis in neurons. We found the CaM-regulated rRNA synthesis is Ca2+-dependent and necessary for nascent protein synthesis and axon growth in hippocampal neurons. Mechanistically, CaM interacts with nucleolar DEAD (Asp-Glu-Ala-Asp) box RNA helicase (DDX21) in a Ca2+-dependent manner to regulate nascent rRNA transcription within nucleoli. We further found CaM alters the conformation of DDX21 to liberate the DDX21-sequestered RPA194, the catalytic subunit of RNA polymerase I, to facilitate transcription of ribosomal DNA. Using high-throughput screening, we identified the small molecules batefenterol and indacaterol that attenuate the CaM-DDX21 interaction and suppress nascent rRNA synthesis and axon growth in hippocampal neurons. These results unveiled the previously unrecognized role of CaM as a messenger to link the activity-induced Ca2+ influx to the nucleolar events essential for protein synthesis. We thus identified the ability of CaM to transmit information to the nucleoli of neurons in response to stimulation.

Key circRNAs from goat: discovery, integrated regulatory network and their putative roles in the differentiation of intramuscular adipocytes.

BACKGROUND: The procession of preadipocytes differentiation into mature adipocytes involves multiple cellular and signal transduction pathways. Recently. a seirces of noncoding RNAs (ncRNAs), including circular RNAs (circRNAs) were proved to play important roles in regulating differentiation of adipocytes. RESULT: In this study, we aimed to identificate the potential circRNAs in the early and late stages of goat intramuscular adipocytes differentiation. Using bioinformatics methods to predict their biological functions and map the circRNA-miRNA interaction network. Over 104 million clean reads in goat intramuscular preadipocytes and adipocytes were mapped, of which16 circRNAs were differentially expressed (DE-circRNAs). Furthermore, we used real-time fluorescent quantitative PCR (qRT-PCR) technology to randomly detect the expression levels of 8 circRNAs among the DE-circRNAs, and our result verifies the accuracy of the RNA-seq data. From the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the DE-circRNAs, two circRNAs, circ_0005870 and circ_0000946, were found in Focal adhesion and PI3K-Akt signaling pathway. Then we draw the circRNA-miRNA interaction network and obtained the miRNAs that possibly interact with circ_0005870 and circ_0000946. Using TargetScan, miRTarBase and miR-TCDS online databases, we further obtained the mRNAs that may interact with the miRNAs, and generated the final circRNA-miRNA-mRNA interaction network. Combined with the following GO (Gene Ontology) and KEGG enrichment analysis, we obtained 5 key mRNAs related to adipocyte differentiation in our interaction network, which are FOXO3(forkhead box O3), PPP2CA (protein phosphatase 2 catalytic subunit alpha), EEIF4E (eukaryotic translation initiation factor 4), CDK6 (cyclin dependent kinase 6) and ACVR1 (activin A receptor type 1). CONCLUSIONS: By using Illumina HiSeq and online databases, we generated the final circRNA-miRNA-mRNA interaction network that have valuable functions in adipocyte differentiation. Our work serves as a valuable genomic resource for in-depth exploration of the molecular mechanism of ncRNAs interaction network regulating adipocyte differentiation.

Impact of pharmacist intervention in reducing vancomycin-associated acute kidney injury: A systematic review and meta-analysis.

AIMS: The aim was to quantify the relationship between pharmacist intervention and vancomycin-associated acute kidney injury (AKI). METHODS: Electronic databases were searched up to August 2020 for meta-analyses of cohort studies and/or randomized controlled trials. Studies that compared the incidence of AKI in patients between post- and prepharmacist intervention were investigated. The primary outcome was incidence of AKI. We also evaluated the influence of pharmacist intervention in risk factors of vancomycin-associated AKI. RESULTS: The search strategy retrieved 1744 studies and 34 studies with 19 298 participants were included (22 published articles and 12 abstracts from conference proceedings). Compared with the preintervention group, the postintervention group patients had a significantly lower incidence of vancomycin-associated AKI: 7.3% for post- and 9.6% for preintervention (odds ratio [OR] 0.52, 95% confidence interval [CI]; 0.41, 0.67], P < .00001). The rate of attaining target concentration was significantly higher in the post- than preintervention group (OR 2.86, 95% CI [2.23, 3.67], P < .00001). The postintervention group significantly improved the percentage of serum creatinine laboratory tests than preintervention group (OR = 3.24, 95% CI 2.02, 5.19], P < .00001). Patients postintervention had markedly lower risk of mortality than preintervention patients (OR 0.47, 95% CI [0.31, 0.72], P = .0004). CONCLUSION: Pharmacist intervention in vancomycin treatment significantly decreased the rate of vancomycin-associated AKI, while improving efficacy and reducing mortality. We speculate that this is because the pharmacist interventions optimized the rationality of vancomycin therapy, monitoring of vancomycin trough concentration and the monitoring of patients' renal function.

High Proton Conduction in Three Highly Water-Stable Hydrogen-Bonded Ferrocene-Based Phenyl Carboxylate Frameworks.

To acquire more new crystalline proton conductive materials, three ferrocene-based phenyl carboxylate frameworks (FCFs), [FcCO(o-C6H4COOH)] (FCF 1) (Fc = (η5-C5H5)Fe(η5-C5H4)), [m-FcC6H4COOH] (FCF 2), and [p-FcC6H4COOH] (FCF 3), supported by hydrogen bonds and π···π interactions were prepared. Their structures and phase purities are clarified by single-crystal X-ray diffraction or powder X-ray diffraction (PXRD). In addition, their high thermal and water stability were confirmed by thermogravimetric analyses, PXRD, and scanning electron microscopy determinations. Proton conductivity (σ) of 1-3 was studied under different relative humidities (RHs) and temperatures, and it was found that their σ boosted with the increase of humidity and temperature. Under 100 °C and 98% RH, their optimal σ values are 0.77 × 10-3, 1.94 × 10-4, and 3.46 × 10-3 S·cm-1, respectively. Consequently, their proton conductive mechanisms were proposed by means of activation energy calculation and structural analysis. Note that they are good proton conductive materials and are expected to be used in proton exchange membrane fuel cells.

Calcineurin inhibitor-associated new-onset diabetes mellitus in chronic kidney disease treatment: a 4-year single-center cross-sectional study in China.

PURPOSE: To identify the risk factors of calcineurin inhibitor (CNI)-associated new-onset diabetes mellitus (NODM) in chronic kidney disease (CKD) treatment. METHODS: We retrospectively screened patients treated with CNIs in our hospital from January 2015 to December 2018. The inclusion criteria were as follows: a clear diagnosis of CKD and patients receiving CNI treatment. We compared patients with and without CNI-associated NODM. RESULTS: Ninety-eight of the 336 assessed patients met the inclusion criteria, 15 (15.3% [15/98]) of whom developed CNI-associated NODM. Multiple logistic regression analysis revealed that baseline glycosylated hemoglobin (OR=4.141; 1.024-16.743; p=0.046) and CNI trough concentration (1 year) (OR=1.028; 1.009-1.047, p=0.004) were independent risk factors for NODM. In contrast, glucocorticoid type (prednisone) (OR=0.075; 0.011-0.526, p=0.009) was identified as an independent protective factor for NODM. Using a receiver operating characteristic curve, a cutoff cyclosporin A trough concentration of 102.1 ng/mL was identified as a predictive factor of NODM. Univariate logistic regression showed that the incidence of diabetes was significantly higher in patients with baseline glycosylated hemoglobin in non-diabetic range but higher than 5.65% (10.2% vs. 29.2%, p=0.038). One NODM patient (6.7% [1/15]) recovered at 12.7 months after the onset of diabetes mellitus. CONCLUSIONS: We recommend that more attention be paid to patients with baseline glycosylated hemoglobin in non-diabetic range but higher than 5.65% during CKD treatment with CNIs. High trough concentrations of cyclosporin A, particularly those >102.1 ng/mL, contribute to NODM. CNI-associated NODM may be reversible in the treatment of CKD.

Cytoskeleton Genes Expression and Survival Rate Comparison Between Immature and Mature Yak Oocyte After OPS Vitrification.

This study was conducted to investigate the effect of vitrification on survival rate and cytoskeleton gene expression during yak oocyte maturation. The yak oocytes were incubated for 0 h [germinal vesicle (GV) stage] and in vitro matured for 24 h [metaphase II (MII) stage] to obtain immature and mature oocytes. Survival rate after vitrification were compared between immature and mature yak oocytes and cytoskeleton-related genes [cytokeratin 8 (CK8), ß-actin (ACTB), and gap junction protein, alpha 1 (GJA1)] were tested by real-time PCR. Our results showed that MII stage survival rate after open pulled straw vitrification (35.60%) is significantly higher than GV stage (25.90%) oocytes. Furthermore, expression of CK8, ACTB, and GJA1 in MII stage oocytes are also significantly higher than GV stage oocytes. In conclusion, our study demonstrated that higher expression of GJA1, CK8, and ACTB in vitrify-warmed MII stage oocytes when compared with GV stage oocytes and such discrepancy might result in higher survival rate in vitrify-warmed MII stage oocytes.

Minimally Modified LDL-Induced Impairment of Endothelium-Dependent Relaxation in Small Mesenteric Arteries of Mice.

Minimally modified low-density lipoprotein (mmLDL) is a well-known risk factor for cardiovascular diseases. The present study was designed to investigate the role of mmLDL in the endothelium-dependent relaxation of mouse mesenteric arteries. A sensitive myograph system was employed to examine the endothelial function of mesenteric arteries. mRNA and protein expression levels were determined using real-time PCR and Western blotting, respectively. The ultramicrostructure of mesenteric vascular beds was investigated using a transmission electron microscope. The results showed that mmLDL significantly impaired the acetylcholine-induced (3 × 10-10 to 1 × 10-4M) endothelium-dependent relaxation of mouse mesenteric arteries with markedly reduced pIC50 (p < 0.05) and Rmax values (p < 0.001). In addition, mmLDL increased the levels of superoxide production and nitrotyrosine concentration and impaired the endothelial microstructure with decreased KCa3.1 and KCa2.3 expression. In conclusion, mmLDL increases superoxide and nitrotyrosine levels, damages endothelial microstructure with decreased KCa3.1 and KCa2.3 expression, and ultimately attenuates relaxation mediated by nitric oxide- and endothelium-derived hyperpolarizing factor.

BIIB021, a novel Hsp90 inhibitor, sensitizes esophageal squamous cell carcinoma to radiation.

BIIB021 is a novel, orally available inhibitor of heat shock protein 90 (Hsp90) that is currently in phase I/II clinical trials. BIIB021 induces the apoptosis of various types of tumor cells in vitro and in vivo. The aim of this study is to investigate the effect of BIIB021 on the radiosensitivity of esophageal squamous cell carcinoma (ESCC). The results indicated that BIIB021 exhibited strong antitumor activity in ESCC cell lines, either as a single agent or in combination with radiation. BIIB021 significantly downregulated radioresistant proteins including EGFR, Akt, Raf-1 of ESCC cell lines, increased apoptotic cells and enhanced G2 arrest that is more radiosensitive cell cycle phase. These results suggest that this synthetic Hsp90 inhibitor simultaneously affects multiple pathways involved in tumor development and progression in the ESCC setting and may represent a better strategy for the treatment of ESCC patients, either as a monotherapy or a radiosensitizer.

Increased expression of macrophage migration inhibitory factor and DJ-1 contribute to cell invasion and metastasis of nasopharyngeal carcinoma.

BACKGROUND AND AIM: Both macrophage migration inhibitory factor (MIF) and DJ-1 protein have been shown to relate with cell invasion and metastasis in tumors. However, the role of DJ-1 in invasion and metastasis of nasopharyngeal carcinoma (NPC) and its relation to MIF expression in NPC are not fully understood. The aim of present study is to determine whether or not MIF and DJ-1 are correlated with tumor invasion and influence a worse outcome in NPC, as well as its related mechanism. METHODS: 125 cases of NPC and 45 normal tissues of nasopharynx were collected. The expression of MIF and DJ-1 in tissue microarray was evaluated by immunohistochemical staining. Correlation between immunostainings and clinicopathological parameters, as well as the follow-up data of patients, was analyzed statistically. The association of MIF and DJ-1 with cell invasion and migration in NPC cell line were evaluated by small interfering RNA (siRNA) transfection, invasion assay and Western blotting. RESULTS: MIF and DJ-1 staining was diffused and strong in tumor cells, whereas they were generally weaker and less common in normal lining epithelia of nasopharynx. High MIF expression in tumor cells (71.2%, 89/125 cases) were significantly associated with advanced clinical stage, lymph node metastasis, and worse prognosis of NPC patients. High expression of DJ-1 (75.2%, 94/125 cases) were closely correlated to lymph node metastasis and MIF high-expression. Only MIF high expression (P = 0.010) and lymph node metastasis (P = 0.004) emerged as strong independent prognostic factors for overall survival of NPC patients. In vitro, down-regulated expression of DJ-1 in NPC cell lines by siRNA was observed to reduce cell migration and invasion potential, however, exogenous MIF promoted cells invasion. CONCLUSIONS: The data provided evidence that increased expression of MIF and DJ-1 induced cell invasion and metastasis of NPC, supporting the idea that MIF and DJ-1 may play important roles as regulators in the progression of NPC.

Metabonomic analysis of Bombyx mori (Heterocera: Bombysidae) treated with acetaminophen.

The feasibility of using Bombyx mori as model animal is attracting more attention. Whether the effect of drugs on the metabolite profiling was consistent with those in mammals was an aspect to evaluate the feasibility of B. mori as model animal. In this study, we used acetaminophen to treat Dazao fifth-instar B. mori, and its metabolites in hemolymph were detected by gas chromatography-mass spectrometry. The corresponding data were processed and analyzed by total model analysis, principal component analysis, partial least squares-discriminant analysis, orthogonal partial least squares-discriminant analysis, and finally, the difference metabolites between acetaminophen group and control group were selected and identified by our reference material database and the National Institute of Standard and Technology database. The results showed that acetaminophen administration induced elevation of metabolites related to energy source, the intermediate of cholesterol synthesis, and the metabolites related to melanization and also induced the decrease of metabolites in pathway of Krebs cycle, the cholesterol, and sitosterol, which suggested that acetaminophen administration inhibited energy metabolism and promoted the expenditure and imbalance of hormone and melanization.

[Establishment of fluorescence labeling and capillary electrophoresis in MSAP for Beijing You chicken].

The DNA methylated states in muscle tissues from Beijing You chicken were analyzed using methylation sensitive amplified polymorphism (MSAP) combined with fluorescence labeling and capillary electrophoresis technology. We optimized the MSAP experimental condition including the genomic DNA concentration, dilution of pre-amplification prod-uct, the internal standard content and the concentrations of selective primers, Mg2+ and dNTPs. Repeated experiments showed that this method can automatically detect the global DNA methylation states in Beijing You chicken, and can be extended to other animals or plants with complex genomes and rich methylation polymorphism.

Elucidating the structure, and composition of bacterial symbionts in the gut regions of wood-feeding termite, Coptotermes formosanus and their functional profile towards lignocellulolytic systems.

The wood-feeding termite, Coptotermes formosanus, presents an efficient lignocellulolytic system, offering a distinctive model for the exploration of host-microbial symbiosis towards lignocellulose degradation. Despite decades of investigation, understanding the diversity, community structure, and functional profiles of bacterial symbionts within specific gut regions, particularly the foregut and midgut of C. formosanus, remains largely elusive. In light of this knowledge gap, our efforts focused on elucidating the diversity, community composition and functions of symbiotic bacteria inhabiting the foregut, midgut, and hindgut of C. formosanus via metagenomics. The termite harbored a diverse community of bacterial symbionts encompassing 352 genera and 26 known phyla, exhibiting an uneven distribution across gut regions. Notably, the hindgut displayed a higher relative abundance of phyla such as Bacteroidetes (56.9%) and Spirochetes (23.3%). In contrast, the foregut and midgut were predominantly occupied by Proteobacteria (28.9%) and Firmicutes (21.2%) after Bacteroidetes. The foregut harbored unique phyla like Candidate phylum_TM6 and Armatimonadetes. At the family level, Porphyromonadaceae (28.1, 40.6, and 53.5% abundance in foregut, midgut, and hindgut, respectively) and Spirochaetaceae (foregut = 9%, midgut = 16%, hindgut = 21.6%) emerged as dominant families in the termite's gut regions. Enriched operational taxonomic units (OTUs) were most abundant in the foregut (28), followed by the hindgut (14), while the midgut exhibited enrichment of only two OTUs. Furthermore, the functional analyses revealed distinct influences of bacterial symbionts on various metabolic pathways, particularly carbohydrate and energy metabolisms of the host. Overall, these results underscore significant variations in the structure of the bacterial community among different gut regions of C. formosanus, suggesting unique functional roles of specific bacteria, thereby inspiring further investigations to resolve the crosstalk between host and microbiomes in individual gut-regions of the termite.

Endobronchial metastasis secondary to renal clear cell carcinoma: A case report.

BACKGROUND: Endobronchial metastases (EBMs) are tumours that metastasise from a malignant tumour outside the lungs to the central and subsegmental bronchi, and are visible under a bronchofibrescope. Most EBMs are formed by direct invasion or metastasis of intrathoracic malignant tumours, such as lung cancer, oesophageal cancer or mediastinum tumours. Renal cell carcinoma (RCC), accounting for 2% to 3% of all tumours, is a common malignant tumour of the urinary system. Renal clear cell carcinoma (RCCC) constitutes the predominant pathological subtype of RCC, comprising approximately 70% to 80% of all RCC cases. RCCC can spread and metastasise through arterial, venous and lymphatic circulation to almost all organs of the body. Moreover, lung, bone, liver, brain and local recurrence are the most common metastatic neoplasms of RCCC. However, EBM from RCCC has a low complication rate and is often misdiagnosed as primary lung cancer. CASE SUMMARY: A 71-year-old male patient who had undergone radical left nephrectomy 7 years prior due to RCCC was referred to our hospital due to a 1-mo history of productive cough. The results of an enhanced chest CT scan indicated the presence of a soft tissue nodule in the upper lobe of the left lung, and flexible bronchoscopy revealed a hypervascular lesion in the bronchus of the left lung's superior lobe. Therefore, the patient underwent thoracoscopic left superior lobe wedge resection, and pathology confirmed EBM from the RCCC. CONCLUSION: EBM from RCCC has a low incidence and no characteristic clinical manifestations in the early stage. If a bronchial tumour is found in a patient with RCCC, the possibility of bronchial metastatic cancer should be considered.

Unusual primary intracranial dural-based poorly differentiated synovial sarcoma with t(X; 18)(p11; q11).

Synovial sarcoma is a rare aggressive neoplasm occurring at any site of the body, mainly in young adults. It may also arise in the CNS but has seldom been reported. We report a case of unusual intracranial synovial sarcoma in a young male patient. Neuroimaging revealed a large gadolinium-enhancing mass was located at the right anterior cranial fossa and was associated with multiple cyst formation. The mass was dural-based and was observed to invade the right orbital apex and ethmoidal bulla. Histologically, the tumor was composed of uniform oval and round cells with scant cytoplasm and indistinct borders. The tumor cells were observed to form densely cellular sheets, but in some areas, the tumor showed hemangiopericytomatous vascular pattern consisting of tumor cells arranged around dilated, thin-walled blood vessels. By immunohistochemistry, vimentin, CD99 and Bcl-2 were diffusely positive in most cells, and a focally weak reactivity for S-100 protein was also observed. However, the tumor cells were negative for cytokeratin (AE1/AE3), CK7, CK8/18, CK19, epithelial membrane antigen, CD34, synaptophysin, GFAP, desmin, myogenin, and smooth muscle actin. Cytogenetic analysis using fluorescence in situ hybridization (FISH) demonstrated a translocation t(X;18)(p11;q11), an aberration specific for synovial sarcoma. A diagnosis of primary dural-based poorly differentiated synovial sarcoma was made. To our knowledge, this is the first report of a poorly differentiated variant of synovial sarcoma occurring in dura mater and confirmed by cytogenetic analysis. The present case indicates that appropriate immunohistochemical analysis, and in particular molecular analysis, are essential for accurately diagnosing small, round-cell neoplasms in unusual locations.

[Probiotics improve obesity-associated dyslipidemia and insulin resistance in high-fat diet-fed rats].

OBJECTIVE: To evaluate the effect of probiotics (bifidobacterium breve and lactobacillus acidophilus) on serum lipid, serum insulin and insulin resistance in high-fat diet (HFD)-induced obese rats. METHODS: Fifty male Sprague-Dawley rats were randomly assigned to a control (n=10) and a high fat diet groups (n=40) and were fed with standard diet and HFD respectively. Four weeks later, thirty-six HFD-induced obese rats were randomly administered with normal saline (NS), bifidobacterium breve and lactobacillus acidophilus daily (n=12 each). Four weeks later, body lengths, body weights and abdomen circumference of rats were measured, blood lipid, glucose and insulin levels were measured, and Lee's index and insulin resistance index were calculated. RESULTS: Body weight, abdomen circumference, Lee's index, fasting glucose, triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL) in the NS-treated HFD group were significantly higher than the control group (P<0.05). The bifidobacterium breve and lactobacillus acidophilus-treated groups had significantly lower levels of body weight, abdomen circumference, Lee's index, fasting glucose, TC, TG and LDL than the NS-treated HFD group (P<0.05), but the levels of the parameters in the bifidobacterium breve and lactobacillus acidophilus-treated groups were significantly higher than the control group (P<0.05). High density lipoprotein (HDL) and insulin sensitivity index in the NS-treated HFD group were significantly lower than the control group (P<0.05). Bifidobacterium breve and lactobacillus acidophilus treatment dramatically increased HDL levels and insulin sensitivity index compared with the NS-treated HFD group (P<0.05), although the levels of the two parameters did not reach to the levels of the control group. There were significant differences in the levels of fasting insulin, insulin resistance index and insulin secretion index between the bifidobacterium breve and lactobacillus acidophilus groups (P<0.05). CONCLUSIONS: Lactobacillus acidophilus and bifidobacterium breve can decrease serum levels of lipid and glucose and improve insulin resistance in obese rats. Bifidobacterium breve seems to be more effective on attenuating insulin resistance than lactobacillus acidophilus.

Integrated Metabolomic and Transcriptomic Analyses Reveal the Potential Regulation of Flavonoids in the Production of Embryogenic Cultures during Early Somatic Embryogenesis of Longan (Dimocarpus longan Lour.).

Embryogenic cultures of longan (Dimocarpus longan Lour.) contain various metabolites with pharmacological properties that may function in the regulation of somatic embryogenesis (SE). In this study, based on widely targeted metabolomics, 501 metabolites were obtained from the embryogenic calli, incomplete compact proembryogenic cultures, and globular embryos during early SE of longan, among which 41 flavonoids were differentially accumulated during the SE. Using RNA sequencing, 36 flavonoid-biosynthesis-related genes and 43 MYB and 52 bHLH transcription factors were identified as differentially expressed genes. Furthermore, Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the flavonoid metabolism-related pathways were significantly enriched during the early SE. These results suggested that the changes in flavonoid levels in the embryogenic cultures of longan were mediated by MYBs and bHLHs via regulating flavonoid-biosynthesis-related genes, thus potentially regulating early SE. The identified metabolites in the embryogenic cultures of longan can be used to develop pharmaceutical ingredients.

Bilateral cerebellar epithelioid hemangioblastoma with possible ependymal differentiation in a patient with von Hippel-Lindau disease.

There are controversies regarding the histogenesis of stromal cells of hemangioblastoma, and no hypothesis has conclusively been proven. We report a case of unusual hemangioblastoma in a middle-aged man with von Hippel-Lindau disease. Neuroimaging revealed multifocal gadolinium-enhancing masses were located within both sides of the cerebellar hemisphere. Histologically, only small areas showing the typical morphology of hemangioblastoma were recognized in masses. Most areas of masses were composed of cohesive epithelioid tumor cells with abundant cytoplasm and distinct boundaries. Epithelioid tumor cells were arranged around blood vessels, exhibiting perivascular anuclear zone structures like ependymoma. The epithelioid tumor cells were diffusely positive for vimentin, CD99, neuron-specific enolase, GFAP and focally positive for epithelial membrane antigen (EMA) and D2-40 in a dot-like pattern. Variable-sized lipid droplets and glycogen particles were noted in the cytoplasm of epithelioid tumor cells under an electron microscope. A diagnosis of epithelioid cellular hemangioblastoma with possible ependymal differentiation (WHO grade I) was made. To our knowledge, only a few cases of hemangioblastoma show epithelioid appearance or EMA immunoreactivity. The present case indicates that the stromal cells of hemangioblastoma might originate from primitive neuroectodermal cells, and they have the capacity to show a distinctive sign of glial or ependymal differentiation.

The effect of postoperative TACE on prognosis of HCC with microscopic venous invasion.

BACKGROUND/AIMS: The aim of this study was to evaluate the clinical efficacy of postoperative adjuvant transcatheter arterial chemoembolization (TACE) on hepatocellular carcinoma (HCC) with microscopic venous invasion. METHODOLOGY: Data from 76 patients with HCC who underwent hepatectomy with or without postoperative adjuvant TACE between July 2005 and August 2010 were retrospectively reviewed. Kaplan-Meier method was used to compare survival between the groups and prognostic factors were evaluated by Cox proportional hazard model. RESULTS: The 1-, 3- and 5-year disease- free survival rates were 76.3%, 44.5% and 31.8%, respectively, for the adjuvant TACE group (35 patients) and 60.1%, 39.3% and 21.5%, respectively, for the control group (41 patients). The 1-, 3- and 5-year overall survival rates were 88.6%, 67.2% and 42.3%, respectively, for the TACE group and 77.5%, 58.0% and 40.5%, respectively, for the control group. Although improving trends of both disease-free survival and overall survival were observed in adjuvant TACE group, there was no significant difference between the two groups (p>0.05). Cox regression analysis revealed that tumor size and differentiation were significant independent prognostic factors. CONCLUSIONS: Postoperative adjuvant TACE may improve 1, 3 and 5 year disease-free and overall survival rates of HCC patients with microscopic venous invasion but no statistical significance was found. It can be used as a preventative treatment but not a routine procedure for such patients.

Genome-wide identification of miRNAs and targets associated with cell wall biosynthesis: Differential roles of dlo-miR397a and dlo-miR408-3p during early somatic embryogenesis in longan.

The dynamic alterations in cell wall (CW) biosynthesis play an essential role in physiological isolation during the plant somatic embryogenesis (SE). However, the mechanisms underlying the functions of cell wall-associated miRNAs (CW-miRNA) remain poorly understood in plant SE. Here, we have identified 36 distinct candidate miRNAs associated with CW biosynthesis from longan third-generation genome as well as miRNA transcriptome, and modified RLM-RACE validated four distinct miRNA, which specifically targeted four CW-related genes. More importantly, we found that the dlo-miR397a-antagomir significantly enhanced DlLAC7 expression and improved laccase activity. Interestingly, inhibition of dlo-miR397a increased CW lignin deposition and promoted the tightening of protodermal cell by miRNA-mimic technology during early SE. Moreover, overexpression of dlo-miR408-3p (dlo-miR408-3p-agomir) markedly decreased DlLAC12 expression. dlo-miR408-3p-agomir activated rapid cell division, thus promoting the globular embryo (GE) development, which might be due to high DNA synthesis activity in protoepidermal cells, rather than affecting lignin synthesis. The subcellular location also indicated that both DlLAC7 and DlLAC12 proteins were primarily localized in CW and regulated CW biosynthesis. Overall, our findings provided new insight on the molecular regulatory networks comprising various miRNAs associated with cell wall, and established that dlo-miR397a and dlo-miR408-3p played differential roles during early SE in longan. The findings also shed some light on the potential role of miRNA target DlLAC regulating in vivo embryonic development of plant.

Identification of a novel linear epitope on EspA from enterohemorrhagic E. coli using a neutralizing and protective monoclonal antibody.

Enterohemorrhagic E. coli (EHEC) causes severe diseases in humans and animals via the production of Shiga toxins, and injection of effectors into epithelia using type III secretion system (TTSS). E. coli secreted protein A (EspA) forms the filamentous conduits of TTSS, which extends into the translocation pore embedded in host cell membranes and aids in the transportation of bacterial effectors. In addition, EspA is closely associated with initial bacterial adhesion and the formation of biofilms. EspA in its various forms elicits protective immune responses, although the epitope responsible has not to be identified. Here we report the presence of a linear, immunogenic, conserved and partially protective epitope E07 (100Lys-120Val) on EspA, which is recognized by the novel monoclonal antibody 1H10. This antibody blocks EHEC-induced actin polymerization and confers protection in mice. These findings provide a better understanding of EspA-induced immune responses and could lead to epitope-based vaccines and antibody-based therapies.