A novel long excitation/emission wavelength fluorophore as platform utilized to construct NIR probes for bioimaging and biosensing.

Near-infrared (NIR) fluorophores, especially dicyano-based fluorophores and xanthene-based hemicyanines, have beenput high expectation in bioimaging application due to their excellent optical properties. However, they suffer from inherentshortagessuch as short excitation/emission wavelength (less than 700 nm) or small Stokes shift (20-50 nm). Herein, we constructed a novel NIR dicyano-based fluorophore (DCO-HBTN). Toourknowledge, it is the first reported dicyano-based fluorophore of which the excitation/emission wavelength is more than 650 nm and Stokes shift is more than 100 nm. To demonstrate the feasibility of our efforts, we developed two NIR fluorescent probes (Probe-Cys and Probe-H2S) based on the fluorophore, Probe-Cys displayed good selective and highly sensitive (LOD = 0.28 µM) recognition of Cys over Hcy and GSH, which was used to visualize endogenous Cys in tumor tissue. Probe-H2S exhibited an. excellent specific and sensitive (LOD = 0.11 µM) response to H2S, which was applied in monitoring H2S releasing from the prodrug in vitro and in vivo.

Off-label use of letrozole in Chinese short pubertal boys: Effectiveness, safety, and exposure-response analysis.

AIMS: Recently, letrozole has been used off-label to treat short pubertal boys. The experience on letrozole effectiveness and safety has been obtained primarily from Caucasian children. A simple extrapolation of the data to Chinese paediatric populations is questionable because of the substantial ethnic differences between the two populations. Therefore, the present study aimed to determine the effectiveness and safety of letrozole use in Chinese short pubertal boys as well as to establish an exposure-response relationship. METHODS: Forty-one Chinese boys were included in the study. Patients were given letrozole tablets (2.5 mg) once daily in combination with growth hormone, and follow-up visits were made after 1, 3, 6 and 12 months of treatment. Plasma samples were taken from clinical examinations and analysed using high performance liquid chromatography with fluorescence detection. RESULTS: After 1 year of treatment, 35 (88%) boys showed increased predicted adult heights. However, possible adverse drug reactions were seen in nine boys (22%). Predicted adult heights increased significantly from 168.4 ± 3.7 to 173.0 ± 4.2 cm, while oestrogen levels dropped from 33.2 ± 7.4 to 21.6 ± 7.3 pg/mL. Increments in predicted adult height were significantly correlated with trough letrozole concentrations (r = 0.39, P = .01). CONCLUSION: Letrozole treatment in Chinese pubertal populations should be further optimized, and more personalized therapies should be developed.

Serial multiple mediation of demoralization and depression in the relationship between hopelessness and suicidal ideation.

OBJECTIVE: Suicidal ideation is common in cancer patients and may be associated with hopelessness, demoralization, and depression. This study aims to investigate the serial multiple mediation of demoralization and depression in the relationship between hopelessness and suicidal ideation in cancer patients. METHODS: A total of 244 cancer patients were investigated by using the following standardized self-reported questionnaires: self-rating idea of suicide scale, Beck hopelessness scale, demoralization scale-Mandarin version, and patient health questionnaire depression scale-9. The mediation hypothesis was tested with a serial multiple mediation model (PROCESS model 6). An exploratory graph analysis was performed to detect the correlations among the dimensions of the mental conditions measured by these instruments. RESULTS: Bootstrap analyzes indicate that there were direct and indirect effects of hopelessness on suicidal ideation mediated solely by demoralization (B = 2.3074, SE = 0.1724, P < .001) or by demoralization together with depression (B = 0.1605, SE = 0.0303, 95% confidence interval [CI] = 0.1102 to 0.2303). The mediation of depression alone in the relationship between hopelessness and suicidal ideation was insignificant (B = 0.1541, SE = 0.0519, 95% CI = -0.0565 to 0.0715). The exploratory graph analysis suggests that the strongest edge of dimensions between demoralization and suicidal ideation was desperation-disheartenment (0.62). CONCLUSIONS: The results of the study support the hypothesis that demoralization and depression mediate between hopelessness and suicidal ideation. The early identification of and interventions for hopelessness, demoralization, and depression may prevent cancer patients from developing suicidal ideation.

Role of MRI in the early diagnosis of tubal ectopic pregnancy.

OBJECTIVE: To determine the role of MRI in the early diagnosis of tubal ectopic pregnancy (EP). METHODS: Clinical and MRI features of 27 cases of tubal pregnancy were reviewed. RESULTS: A thick-walled gestational sac (GS)-like structure was demonstrated lateral to the uterus in all cases. On T2-weighted images, the thick wall typically exhibited 3 discrete rings in 22 cases (81 %), among which 17 cases (63 %) displayed small vessels and 6 cases (33 %) exhibited small areas of fresh haemorrhage inside the thick wall. The contents demonstrated non-specific liquid in 26 %, papillary solid components in 56 %, and fresh blood or fluid-fluid level in 19 % of the cases. Dilatation of the affected fallopian tube associated with hematosalpinx was demonstrated in 18 cases (67 %) and marked enhancement of the tubal wall was observed in 22 cases (81 %). No correlation was found between the size of the GS and the estimated gestational age (r = 0.056). CONCLUSION: MRI plays an important role in the early diagnosis and management of tubal pregnancy. The characteristic MRI features include a GS-like structure with a "three rings" appearance on T2-weighted images, presence of solid components in the sac, dilatation of the affected fallopian tube with hematosalpinx, and tubal wall enhancement. KEY POINTS: • MR imaging has served as a problem-solving procedure in ectopic pregnancy. • MR imaging features can be criteria for early diagnosis of tubal pregnancy. • Detailed assessment of ectopic implantation is necessary for management decision-making.

[Mechanism of Polypeptide Extract from Scorpion Venom Combined Rapamycin in Enhancing Autophagy of H22 Hepatoma Cells: an Experimental Study].

OBJECTIVE: To observe enhanced effects of polypeptide extract from scorpion venom (PESV) combined Rapamycin on autophagy of H22 hepatoma cells in mice and to explore its possible mechanism. METHODS: The H22 hepatocarcinoma cell suspension was subcutaneously inoculated into 40 Kunming mice. Then tumor-bearing mice were randomly divided into four groups, i.e., the control group,the high dose PESV group, the low dose PESV group, and the combination group (high dose PESV + Rapamycin), 10 in each group. Mice in high and dose PESV groups were administered with 20 mg/kg and 10 mg/kg PESV respectively by gastrogavage. Mice in the combination group were administered with 2 mg/kg rapamycin and 20 mg/kg PESV by gastrogavage. The intervention lasted for 14 successive days. The tumor volume was measured once every other day, the tumor growth curve was drawn, and then the tumor inhibitory rate calculated. Pathological changes of the tumor tissue were observed by HE staining. Protein expression levels of mammal target of rapamycin (mTOR), UNC-51-like kinase-1 (ULK1), microtubule-associated protein1 light chain3 (MAPILC3A), and Beclin1 were detected by immunohistochemical assay. RESULTS: The growth of H22 hepatoma transplantation tumor was inhibited in high and low dose PESV groups and the combination group (P < 0.05). And there was statistical difference in tumor weight and tumor volume between the combination group and high and low dose PESV groups (P < 0.05). There was no statistical difference in tumor weight or tumor volume between the high dose PESV group and the low dose PESV group (P > 0.05). lmmunohistochemical assay showed that the protein expression of mTOR was higher, but protein expressions of ULK1, MAP1LC3A, Beclin1 were lower in the control group than in the rest 3 groups (P < 0.05, P < 0.01). Compared with the high dose PESV group, protein expressions of ULK1, MAP1LC3A, and Beclin1 were obviously lower (P < 0.05). CONCLUSION: PESV combined Rapamycin might inhibit the development of H22 hepatoma transplantation tumor in mice possibly through inhibiting the activity of mTOR, enhancing expressions of ULK1, MAP1LC3A, and Beclin1.

Swallowing rehabilitation of patients undergoing T-tube implantation for the treatment of laryngotracheal stenosis.

OBJECTIVE: Patients with laryngotracheal stenosis (LTS) often have dysphagia after laryngotracheal reconstruction with T-tube insertion, which affects the quality of life. The purpose of this study is to observe the effect of swallowing rehabilitation therapy on the improvement of quality of life in patients of otolaryngology-head and neck surgery with dysphagia undergoing T-tube implantation treatment through longitudinal study. METHODS: Thirty-eight patients with LTS who experienced dysphagia after laryngotracheal reconstruction and T-tube implantation were recruited. All patients received swallowing rehabilitation therapy. The assessment of swallowing function was performed using the 10-item Eating Assessment Tool (EAT-10), the 30 mL water swallow test (WST), and flexible endoscopic evaluation of swallow (FEES). RESULTS: After swallowing rehabilitation therapy, timing of swallowing, grade of dysphagia, performance on FEES and 30 mL WST, and EAT-10 score all improved. Thirty-eight patients successfully transitioned to oral feeding and were able to remove their nasogastric tubes without experiencing any complications, including aspiration pneumonia. CONCLUSION: For patients with LTS who experienced dysphagia after laryngotracheal reconstruction and T-tube implantation, swallowing rehabilitation therapy could improve swallowing function of the patients, so as to reduce the potential harm caused by the pain and complications of surgery experienced by patients.

Recombinant adeno-associated virus 8-mediated inhibition of microRNA let-7a ameliorates sclerosing cholangitis in a clinically relevant mouse model.

BACKGROUND: Primary sclerosing cholangitis (PSC) is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment options. Recombinant adeno-associated virus (rAAV) provides a promising platform for gene therapy on such kinds of diseases. A microRNA (miRNA) let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been evaluated. AIM: To investigate the therapeutic effects of inhibition of a miRNA let-7a transferred by recombinant adeno-associated virus 8 (rAAV8) on a xenobiotic-induced mouse model of sclerosing cholangitis. METHODS: A xenobiotic-induced mouse model of sclerosing cholangitis was induced by 0.1% 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine (DDC) feeding for 2 wk or 6 wk. A single dose of rAAV8-mediated anti-let-7a-5p sponges or scramble control was injected in vivo into mice onset of DDC feeding. Upon sacrifice, the liver and the serum were collected from each mouse. The hepatobiliary injuries, hepatic inflammation and fibrosis were evaluated. The targets of let-7a-5p and downstream molecule NF-κB were detected using Western blot. RESULTS: rAAV8-mediated anti-let-7a-5p sponges can depress the expression of let-7a-5p in mice after DDC feeding for 2 wk or 6 wk. The reduced expression of let-7a-5p can alleviate hepato-biliary injuries indicated by serum markers, and prevent the proliferation of cholangiocytes and biliary fibrosis. Furthermore, inhibition of let-7a mediated by rAAV8 can increase the expression of potential target molecules such as suppressor of cytokine signaling 1 and Dectin1, which consequently inhibit of NF-κB-mediated hepatic inflammation. CONCLUSION: Our study demonstrates that a rAAV8 vector designed for liver-specific inhibition of let-7a-5p can potently ameliorate symptoms in a xenobiotic-induced mouse model of sclerosing cholangitis, which provides a possible clinical translation of PSC of human.

Defective natriuresis contributes to hyperkalemia in db/db mice during potassium supplementation.

OBJECTIVES: Potassium supplementation reduces blood pressure and the occurrence of cardiovascular diseases, with K+-induced natriuresis playing a potential key role in this process. However, whether these beneficial effects occur in diabetes remains unknown. METHODS: In this study, we examined the impact of high-K+ intake on renal Na+/K+ transport by determining the expression of major apical Na+ transporters, diuretics responses (as a proxy for specific Na+ transporter function), urinary Na+/K+ excretion, and plasma Na+/K+ concentrations in db/db mice, a model of type 2 diabetes mellitus. RESULTS: Although db/m mice exhibited increased fractional excretion of sodium (FENa) and fractional excretion of potassium (FEK) under high-K+ intake, these responses were largely blunted in db/db mice, suggesting impaired K+-induced natriuresis and kaliuresis in diabetes. Consequently, high-K+ intake increased plasma K+ levels in db/db mice, which could be attributed to the abnormal activity of sodium-hydrogen exchanger 3 (NHE3), sodium-chloride cotransporter (NCC), and epithelial Na+ channel (ENaC), as high-K+ intake could not effectively decrease NHE3 and NCC and increase ENaC expression and activity in the diabetic group. Inhibition of NCC by hydrochlorothiazide could correct the hyperkalemia in db/db mice fed a high-K+ diet, indicating a key role for NCC in K+-loaded diabetic mice. Treatment with metformin enhanced urinary Na+/K+ excretion and normalized plasma K+ levels in db/db mice with a high-K+ diet, at least partially, by suppressing NCC activity. CONCLUSION: Collectively, the impaired K+-induced natriuresis in diabetic mice under high-K+ intake may be primarily attributed to impaired NCC-mediated renal K+ excretion, despite the role of NHE3.

Eleven new highly oxygenated triterpenoids from the leaves and stems of Schisandra chinensis.

Eleven new triterpenoids, schinchinenins A­H (1­8) and schinchinenlactones A­C (9­11) together with three known triterpenoids, henrischinins A­C (12­14), were isolated from the leaves and stems of Schisandra chinensis by bioassay-guided fractionation. Schinchinenin A (1) is the first example of a highly oxygenated triterpenoid characterized by a 5/5/7/6/5-fused pentacyclic ring and a 3-one-2-oxabicyclo[3.2.1]-octane moiety. Schinchinenins E and F (5 and 6) are highly oxygenated triterpenoids that contain a hydroperoxyl moiety, which is rare in compounds from the Schisandra genus. The structures and stereochemistry of 1­11 were elucidated using spectroscopic analysis, single-crystal X-ray diffraction, computational optical rotation, chemical transformation, and CD exciton chirality methods. The activities of compounds 1, 2, 7, and 12­14 against HSV-2 and adenovirus were evaluated for the first time, and of these compounds, 13 was the most active inhibitor of HSV-2, with a selectivity index value as high as 29.95.

[Formulation optimization of ginkgo flavonoids matrix tablets by orthogonal design].

Sustained-release tablet has become one of the hottest research spots in the area of sustained release preparations with its unique advantages. At present, a series of shortcomings were exited in the ordinary ginkgo preparations, which were used for the treatment of cardiovascular and cerebrovascular diseases. In order to avoid these shortcomings, ginkgo flavonoids matrix tablets were prepared in this paper. Furthermore, the amount and varieties of matrix material, adhesives and fillers were investigated. Meanwhile, the formulation was optimized by using the method of orthogonal design, and Zero-order, First-order, Higuchi, Ritger-peppas equation were used for the model fitting and mechanism discussing of drug release.

Dynamic changes in cardiac morphology, function, and diffuse myocardial fibrosis duration of diabetes in type 1 and type 2 diabetic mice models using 7.0 T CMR and echocardiography.

Background: Diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD). Hence, early detection of cardiac changes by imaging is crucial to reducing cardiovascular complications. Purpose: Early detection of cardiac changes is crucial to reducing cardiovascular complications. The study aimed to detect the dynamic change in cardiac morphology, function, and diffuse myocardial fibrosis(DMF) associated with T1DM and T2DM mice models. Materials and methods: 4-week-old C57Bl/6J male mice were randomly divided into control (n=30), T1DM (n=30), and T2DM (n=30) groups. A longitudinal study was conducted every 4 weeks using serial 7.0T CMR and echocardiography imaging. Left ventricular ejection fraction (LV EF), tissue tracking parameters, and DMF were measured by cine CMR and extracellular volume fraction (ECV). Global peak circumferential strain (GCPS), peak systolic strain rate (GCPSSR) values were acquired by CMR feature tracking. LV diastolic function parameter (E/E') was acquired by echocardiography. The correlations between the ECV and cardiac function parameters were assessed by Pearson's test. Results: A total of 6 mice were included every 4 weeks in control, T1DM, and T2DM groups for analysis. Compared to control group, an increase was detected in the LV mass and E/E' ratio, while the values of GCPS, GCPSSR decreased mildly in DM. Compared to T2DM group, GCPS and GCPSSR decreased earlier in T1DM(GCPS 12W,P=0.004; GCPSSR 12W,P=0.04). ECV values showed a significant correlation with GCPS and GCPSSR in DM groups. Moreover, ECV values showed a strong positive correlation with E/E'(T1DM,r=0.757,P<0.001;T2DM, r=0.811,P<0.001). Conclusion: The combination of ECV and cardiac mechanical parameters provide imaging biomakers for pathophysiology, early diagnosis of cardiac morphology, function and early intervention in diabetic cardiomyopathy in the future.

Triterpenoids and lignans from Schisandra chinensis and their inhibition activities of Cdc25A/B phosphatases.

Three new highly modified lanostane triterpenoids schisanchinlactone A-C (1-3), together with six known compounds (4-9) were isolated from the stems and leaves of Schisandra chinensis. Their structures were established by extensive spectroscopic analyses. Compounds 7 and 8 showed significant inhibition of Cdc25A phosphatase with inhibitory rates of 85.5% and 98.1%, respectively, at the concentration of 100 µM.

Radiation Therapy Promotes Hepatocellular Carcinoma Immune Cloaking via PD-L1 Upregulation Induced by cGAS-STING Activation.

PURPOSE: Radiation therapy (RT) is one of the main treatments for patients with unresectable hepatocellular carcinoma (HCC). Emerging evidence indicates that the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) stimulator of interferon gene (STING) pathway is crucial in RT-induced antitumor immune responses. Here, we discovered that activation of the cancer cell-intrinsic cGAS-STING pathway mediated immune cloaking after RT-induced DNA damage. METHODS AND MATERIALS: Key regulatory proteins in the cGAS-STING signaling pathway in human and murine HCC cell lines were knocked out or down using CRISPR and CRISPR-associated protein 9 or small interfering RNA. The underlying mechanism of immune cloaking and clinical significance of cGAS-STING-induced programmed cell death ligand 1 (PD-L1) expression were studied with both ex vivo analyses and in vitro experiments. RESULTS: RT upregulated PD-L1 in patients with HCC, which correlated with poor survival. RT activated cGAS-STING, increasing immune-checkpoint PD-L1 expression in human and mouse liver cancer cells. Ionizing radiation activated the STING-TANK-binding kinase 1 (TBK1)-interferon regulatory factor 3 (IRF3) innate immune pathway, leading to PD-L1 upregulation in HCC cells and inhibiting cytotoxic T-lymphocyte activity and protecting tumor cells from immune-mediated eradication. Knockdown of cGAS, STING, TBK1, and IRF3 reversed the antitumor effect of cytotoxic T-lymphocyte-mediated cytotoxicity after ionizing radiation in vitro or in vivo. RT potentiated the antitumor effect of programmed cell death protein 1 and PD-L1 axis blockade and augmented cytotoxic T-cell (CTL) infiltration in HCC tumors in immunocompetent mice. CD8 depletion compromised the synergetic antitumor effect of combined RT and anti-PD-L1 blockade, demonstrating that CD8+ CTLs are required for antitumor immunity induced by combination therapy. CONCLUSIONS: Our results identified an immune-cloaking mechanism for RT-activated, innate immune cGAS-STING and suggested that RT enhances HCC immunotherapy.

Clonorchis sinensis infection induces hepatobiliary injury via disturbing sphingolipid metabolism and activating sphingosine 1-phosphate receptor 2.

Clonorchis sinensis (C. sinensis) infection induces severe hepatobiliary injuries, which can cause inflammation, periductal fibrosis, and even cholangiocarcinoma. Sphingolipid metabolic pathways responsible for the generation of sphingosine-1-phosphate (S1P) and its receptor S1P receptors (S1PRs) have been implicated in many liver-related diseases. However, the role of S1PRs in C. sinensis-mediated biliary epithelial cells (BECs) proliferation and hepatobiliary injury has not been elucidated. In the present study, we found that C. sinensis infection resulted in alteration of bioactive lipids and sphingolipid metabolic pathways in mice liver. Furthermore, S1PR2 was predominantly activated among these S1PRs in BECs both in vivo and in vitro. Using JTE-013, a specific antagonist of S1PR2, we found that the hepatobiliary pathological injuries, inflammation, bile duct hyperplasia, and periductal fibrosis can be significantly inhibited in C. sinensis-infected mice. In addition, both C. sinensis excretory-secretory products (CsESPs)- and S1P-induced activation of AKT and ERK1/2 were inhibited by JTE-013 in BECs. Therefore, the sphingolipid metabolism pathway and S1PR2 play an important role, and may serve as potential therapeutic targets in hepatobiliary injury caused by C. sinensis-infection.

[Expression of high mobility group protein-B1 in mice with hyperoxia-induced bronchopulmonary dysplasia].

OBJECTIVE: To study the effect of hyperoxia exposure on high mobility group protein-B1 (HMGB1) expression in neonatal mice and the role of HMGB1 in the pathogenesis of bronchopulmonary dysplasia (BPD). METHODS: C57BL/6 mice were randomly exposed to 60% O2 or air 1 day after birth. BPD was induced by 60% O2 exposure. The pulmonary tissue samples were harvested 3, 7 and 14 days after exposure. The pathologic changes of pulmonary tissues were observed by hematoxylin and eosin staining, Masson staining and radical alveolar count. The expression of HMGB1 protein in lungs was detected by immunofluorescence. The expression of HMGB1 mRNA was detected by real-time fluorescent quantitative PCR. RESULTS: In the BPD group, the lungs developed decreased alceolar septation, swollen alveolar epithelium, stroma edema, interstitial fibrosis and developmental lag when compared with the control group. These changes became more obvious with more prolonged hyperoxia exposure. The expression of HMGB1 protein and mRNA 7 and 14 days after exposure increased significantly in the BPD group compared with that in the control group. CONCLUSIONS: Hyperoxia exposure results in an increase in lung HMGB1 expression. The increased HMGB1 expression may be associated with the development of BPD.

The Association of New-Onset Atrial Fibrillation and Risk of Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: There are distinct results for the relationship between new-onset atrial fibrillation (NOAF) and subsequent incident cancer. To date, no systematic analysis has been conducted on this issue. This study aims to explore the relationship between NOAF and the risk of developing cancer through a meta-analysis with a large sample size. METHODS: Electronic databases, such as PubMed and EMBASE, were searched for published relevant studies on NOAF patients diagnosed with cancer after and during follow-ups, including reported records of baseline information and the statistical result of morbidity. Two investigators independently reviewed the articles and extracted the data using uniform standards and definitions. The meta-analysis was conducted using the Cochrane Program Review Manager. RESULTS: This meta-analysis consisted of five cohort studies and one case-control study, which comprised 533,514 participants. The pooled relative risk (RR) for incident cancer was 1.24 (95% CI: 1.10-1.39, P=0.0003). The temporal trend analysis demonstrated that an increased risk of cancer was observed during the initial 90 days (RR: 3.44, 95% CI: 2.29-5.57, P < 0.00001), but not after that. Lung cancer (RR: 1.51, 95% CI: 1.47-1.55, P < 0.00001) was associated with NOAF, but not colorectal cancer and breast cancer. CONCLUSION: This meta-analysis provides evidence that NOAF is associated with increased risk of cancer. The risk of incident cancer particularly increases within 90 days after NOAF diagnosis, but not after that.

Long Noncoding RNA H19 Participates in the Regulation of Adipose-Derived Stem Cells Cartilage Differentiation.

Adipose-derived stem cells (ADSCs) are multipotent and have received increasing attention for their applications in medicine. Cell-based therapies are optimal for diseases with loss or damage to tissues or organs. ADSCs and bone marrow mesenchymal stem cells (BMSCs) can differentiate into many cell lineages. Because of their advantages in accessibility and volume, ADSCs are regarded as a desirable alternative to BMSCs. In this study, we focused on the chondrocytic differentiation potential of ADSCs and the underlying mechanism. We found that the long noncoding RNA H19 plays an important role in this process. Overexpression of H19 in ADSCs induced differentiation towards chondrocytes. H19 is abundantly expressed during embryonic development and downregulated after birth, implying its regulatory role in determining cell fate. However, in our experiments, H19 exerted its regulatory function during cartilage differentiation of ADSCs through competing miRNA regulation of STAT2.

Long Read Single-Molecule Real-Time Sequencing Elucidates Transcriptome-Wide Heterogeneity and Complexity in Esophageal Squamous Cells.

Esophageal squamous cell carcinoma is a leading cause of cancer death. Mapping the transcriptional landscapes such as isoforms, fusion transcripts, as well as long noncoding RNAs have played a central role to understand the regulating mechanism during malignant processes. However, canonical methods such as short-read RNA-seq are difficult to define the entire polyadenylated RNA molecules. Here, we combined single-molecule real-time sequencing with RNA-seq to generate high-quality long reads and to survey the transcriptional program in esophageal squamous cells. Compared with the recent annotations of human transcriptome (Ensembl 38 release 91), single-molecule real-time data identified many unannotated transcripts, novel isoforms of known genes and an expanding repository of long intergenic noncoding RNAs (lincRNAs). By integrating with annotation of lincRNA catalog, 1,521 esophageal-cancer-specific lincRNAs were defined from single-molecule real-time reads. Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that these lincRNAs and their target genes are involved in a variety of cancer signaling pathways. Isoform usage analysis revealed the shifted alternative splicing patterns, which can be recaptured from clinical samples or supported by previous studies. Utilizing vigorous searching criteria, we also detected multiple transcript fusions, which are not documented in current gene fusion database or readily identified from RNA-seq reads. Two novel fusion transcripts were verified based on real-time PCR and Sanger sequencing. Overall, our long-read single-molecule sequencing largely expands current understanding of full-length transcriptome in esophageal cells and provides novel insights on the transcriptional diversity during oncogenic transformation.

Association between B vitamins and schizophrenia: A population-based case-control study.

To explore the association between schizophrenia and six types of B vitamins, including choline, biotin, riboflavin, pyridoxamine, pyridoxine and nicotinamide, based on the hydrophilic interaction liquid chromatography column (HILIC) Liquid Chromatography-Mass Spectrometry (LC-MS) platform. We conducted the case-control study between November 2015 and September 2016 in Weifang, Shandong Province, China. Blood samples from 128 cases of schizophrenia and 101 controls were collected, and B vitamin were measured by LC-MS coupled with HILIC. The HILIC UPLC-MS based analysis of serum B vitamins levels from 128 cases (30 cases with first-episode, 98 cases with relapse) and 101 controls were performed. The results indicated that lower pyridoxine level and schizophrenia was related. (total cases versus controls: ß= -0.215, 95% CI: -0.271, -0.125, p < 0.001; first-episode cases versus controls: ß = -0.190, 95% CI: -0.277, -0.103, p < 0.001). Higher nicotinamide level was also associated with schizophrenia after adjusting confounders (ß = 0.343, 95% CI: 0.022, 0.664, p = 0.036). Other four B vitamins, including biotin, riboflavin, pridoxamine and choline, were showed no statistically difference in cases versus controls, first episode cases versus relapse cases. Two types of B Vitamins, pyridoxine and nicotinamide, show significant association with the schizophrenia.

[SR 59230A on the expression of MicroRNAs in myocardium of heart failure rats].

OBJECTIVE: To investigate the effects of ß3-adrenoceptors(ß3-AR) inhibitor SR 59230A on MicroRNAs expression in rat myocardium with chronic heart failure and the related mechanisms. METHODS: One hundred male SD rats were randomly divided into sham operated group(40)and chronic heart failure(CHF)group(60). Coronary artery ligation was used to induce CHF. Then the rats in CHF group were further randomly divided into CHF control group and CHF+SR 59230A group (CHF+SR). Rats in the sham group were divided into sham control group and sham+SR 59230A group (Sham+SR). The rats in Sham+SR group and CHF+SR group were treated with 1 ml SR 59230A(85 mmoL/L in 0.9% saline)twice a day for seven weeks by intraperitoneal injection, while the rats in control groups were injected with the same amount of saline for seven weeks separately. miScript miRNA PCR Arrays were used to determine the expression profile of MicroRNAs. Immunohistochemistry was used to evaluate the distribution of the related proteins in the heart tissue sections. Western blot was used to detect the expressions of nuclear factor-kappaB(NF-κB),p53 and p53-Phospho-Serine 15 in the heart. RESULTS: ①After in vivo blockade of ß3-AR by SR 59230A, there were 18MicroRNAs down-regulated in sham control group and CHF control group. Within them, 6 MicroRNAs were related to NF-κB signaling pathway, they were miR-125b-5p,miR-143-3p,miR-145-5p,miR-26a-5p,miR-30a-5p and miR-320-5p. ②Slides from the heart tissue showed that NF-κB was distributed both in nucleus and cytoplasm, while p53 in cytoplasm was more than that in nucleus in heart tissue sections. The expressions of NF-κB and p53 were higher in the CHF control group than those in the sham control group(P<0.05), but were lower in CHF+SR group than those in CHF control group(P<0.05),while they were elevated in Sham+SR group compared to the sham control group(P<0.05). ③ Compared with the sham control group, the protein expression of NF-κB p65 was increased significantly in the CHF control group (P<0.05). After treated with SR59230A in vivo,the protein expressions of NF-κB and p53-Phospho-Serine 15 were decreased significantly in CHF rats(P<0.05),while the protein expressions of NF-κB, p53 and p53-Phospho-Serine 15 proteins were increased in the sham rats (P<0.05). CONCLUSIONS: Blocking of ß3-AR improved the damaged heart in CHF rats; ß3-AR caused the change of MicroRNAs expression, and it related to NF-κB signal pathway.