Knockout of SWS2 in zebrafish (Danio rerio) reveals its roles in feeding and phototactic behaviors.

Common ancestor of vertebrates had four cone opsin subfamilies to obtain color vision: ultraviolet-sensitive (SWS1), blue-sensitive (SWS2), middle wavelength sensitive (RH2) and long wavelength sensitive (LWS). Nevertheless, eutherian mammals had lost the SWS2 and RH2 opsins during their nocturnal lifestyle. Many studies had demonstrated the role of SWS1 and LWS cones in feeding, mate choice and skin pigment cell formation. However, the role of SWS2 and RH2 cones remain elusive. In the present study, we used an ideal model visual system, zebrafish, which still have the four cone opsins, to generate a SWS2 knockout zebrafish line. Through various behavioral test, we found that sws2-/- zebrafish larvae exhibited increased food intake compared with WT. Additionally, there were significantly increased the gene expression of phototransduction pathways in sws2-/- zebrafish larvae. Compared to WT, mutant zebrafish showed weaker phototaxis of red light and changed sensitivity of yellow, red and blue lights. But both mutant and WT zebrafish preferred the red light than other wavelengths of light. Taken together, we proposed that SWS2 cone is not necessary for feeding and phototaxis in zebrafish.

Multidimensional isotope analysis of carbon, hydrogen, and oxygen as a tool for traceability of lactose in drug products.

Lactose is one of the most commonly used pharmaceutical excipients. Depending on manufactures, the properties of lactose are very different, which could impact the pharmacokinetic behavior of drug products. Therefore, it is very important to trace the origin of pharmaceutical lactose in drug products which is valuable for prescription analysis. In this study, the carbon, hydrogen and oxygen isotope ratios (δ13C, δ2H and δ18O) of thirty-four lactose from seven manufacturers were analyzed by elemental analysis-stable isotope ratio mass spectrometry (EA-IRMS). One-way analysis of variance (ANOVA) and Duncan's test indicated significant differences in isotope ratios of lactose from different origins. To identify the lactose manufacturer, a discrimination model was generated through linear discriminant analysis (LDA). Based on this model, the manufacturers of lactose used in three drug products were successfully identified. Our results suggested that the multidimensional analysis of δ13C, δ2H and δ18O of lactose provided a fast and effective method to trace the lactose manufacturer. In conclusion, this method can be used to analyze the prescription of the drug product quickly, which could speed up the development of generic drug product.

The role of circular RNAs in brain and stroke.

Circular RNAs are single-stranded RNAs which are closed by covalent bonds during splicing. Different from other RNAs, circular RNAs are well known due to their circular structure. In recent years, many researches were conducted to investigate the role of circular RNAs in multiple diseases. To better understand the structure of circular RNAs, we reviewed the biogenesis and related regulation at first. Mechanisms by which circular RNAs exert effects were summarized then. Due to the conserved and brain-specific characteristic, circular RNAs in brain were depicted next. At last, considering the high mortality rate and disability rate caused by stroke globally, we reviewed related articles and summarized the results of original articles. Circular RNAs are suggested to be involved in the pathogenesis of stroke as well as some other neurological diseases which provides new insights and potential targets in clinical application.

Genetic polymorphisms in pri-let-7a-2 are associated with ischemic stroke risk in a Chinese Han population from Liaoning, China: a case-control study.

Ischemic stroke is a complicated disease, and its pathogenesis has been attributed to the occurrence of genetic polymorphisms. Evidence has suggested that the microRNA let-7a is involved in the pathogenesis of ischemic stroke. Pri-miRNA is the primary transcript, which undergoes several processing steps to generate pre-miRNA and, later, mature miRNAs. In this case-control study, we analyzed the distribution of pri-let-7a-2 variants in patients at a high risk for ischemic stroke and the interactions of pri-let-7a-2 variants and environmental factors. Blood samples and clinical information were collected from 1086 patients with ischemic stroke and 836 healthy controls between December 2013 and December 2015 at the First Affiliated Hospital of China Medical University. We found that the rs1143770 CC genotype and the C allele were associated with a decreased risk of ischemic stroke, whereas the rs629367 CC genotype was associated with an increased risk for ischemic stroke. Moreover, these two single-nucleotide polymorphisms were in linkage disequilibrium in this study sample. We analyzed gene-environment interactions and found that rs1143770 exerted a combined effect on the pathogenesis of ischemic stroke, together with alcohol use, smoking, and a history of hypertension. Therefore, the detection of pri-let-7a-2 polymorphisms may increase the awareness of ischemic stroke risk. This study was approved by the Institutional Ethics Committee of the First Affiliated Hospital of China Medical University, China (approval No. 2012-38-1) on February 20, 2012, and was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-COC-17013559) on December 27, 2017.

Eight new flavonoids from the fruits of Daemonorops draco.

Eight new flavonoids daemoflavans A-H, including two dimeric proanthocyanidins (1 and 2), four flavans (3-6), two 2-arylbenzofurans (7 and 8), along with nine known compounds (9-17), were isolated from the fruit of Daemonorops draco. Their structures, including the absolute configurations, were elucidated by extensive spectroscopic data, ECD analysis, and X-ray crystal diffraction. Besides, the X-ray crystal data of a known compound dracoflavan B1 (9) was firstly reported. Daemoflavan G (7) represents a rare example of C-5 methylated 2-arylbenzofuran in natural products. Among the known compounds, 15, 16, 17 were reported from this species for the first time. All the compounds were evaluated for their cytotoxicity against HepG2 cell line. Among them, compounds 1, 9 and 10 exhibited modest cytotoxic activity with IC50 values of 12.4, 12.0 and 13.2 µM, respectively.

Stilbenoids from aerial parts of Dendrobium plicatile.

Chemical investigation of Dendrobium plicatile Lindl resulted in the isolation and identification of one new bibenzyl, 2-chloro-3, 4'-dihydroxy-3',5-dimethoxybibenzyl (1), as well as 15 known stilbenoids. The structures of this new compound was elucidated by extensive spectroscopic analysis, including HRESIMS, 1H and 13C NMR, DEPT, HMBC, COSY, HMQC, NOESY. Compounds 2, 3 and 5 were obtained from this genus for the first time, compounds 8, 10, 13 and 14 were obtained from this plant for the first time. In addition, the new compound exhibited potent cytotoxic activities against the human breast cancer (MDA-MB231) cell line, the hepatocellular carcinoma (HepG2) cell line and the human lung carcinoma (A549) cell line, with IC50 3.41, 3.02, 2.80 µM, respectively.

Feasibility of terahertz imaging for discrimination of human hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, and novel methods for early/rapid diagnosis of HCC are needed. Terahertz (THz) spectroscopy is considered to have the potential to distinguish between normal liver tissue and HCC tissue; however, there are few reports on it. We conduct this observational study to explore the feasibility of THz imaging for the diagnosis of HCC. AIM: To evaluate the feasibility of THz for discriminating between HCC and normal liver tissues using fresh tissue specimens obtained from HCC patients who had undergone surgery. METHODS: Normal liver tissue and HCC tissue were cryosectioned into 50 µm-thick slices and placed on cover glass. Two adjacent tissue sections were separated subjected to histopathological examination by hematoxylin and eosin staining or THz transmission examination, and THz images were compared with pathologically mapped images. We determined the typical tumor and normal liver tissue regions by pathological examination; the corresponding areas of adjacent sections were examined by THz transmission. RESULTS: The transmission rate of HCC tissue was 0.15-0.25, and the transmission rate of typical HCC tissue was about 0.2. THz transmittance in normal liver tissue is slightly higher than 0.4, but there were many influencing factors, including the degree of liver cirrhosis, fat components, ice crystals in frozen sections, and apoptosis. CONCLUSION: In conclusion, this study shows that THz imaging can detect HCC tissue. Further research will yield more detailed data of the THz transmission rates of HCC tissue with different degrees of differentiation.

Signaling related with biphasic effects of bisphenol A (BPA) on Sertoli cell proliferation: a comparative proteomic analysis.

BACKGROUND: Biphasic effects on cell proliferation of bisphenol A (BPA) can occur at lesser or greater exposures. Sertoli cells play a pivotal role in supporting proliferation and differentiation of germ cells. The mechanisms responsible for inverse effects of great and low concentrations of BPA on Sertoli cell proliferation need further study. METHODS: We utilized proteomic study to identify the protein expression changes of Sertoli TM4 cells treated with 10(-8)M and 10(-5)M BPA. The further mechanisms related to mitochondria, energy metabolism and oxidative stress were investigated by qRT-PCR and Western-blotting analysis. RESULTS: Proteomic studies identified 36 proteins and two major clusters of proteins including energy metabolism and oxidative stress expressed with opposite changes in Sertoli cells treated with 10(-8)M and 10(-5)M BPA, respectively, for 24h. Exposure to 10(-5)M BPA resulted in greater oxidative stress and then inhibited cell proliferation, while ROS scavenger NAC effectively blocked these effects. Exposure to 10(-8)M BPA caused higher intercellular ATP, greater activities of mitochondria, and resulted in significant proliferation of TM4 cells, while oligomycin A, an inhibitor of ATP synthase, abolished these growth advantages. CONCLUSIONS: Our study demonstrated that micromolar BPA inhibits proliferation of Sertoli cells by elevating oxidative stress while nanomolar BPA stimulates proliferation by promoting energy metabolism. GENERAL SIGNIFICANCE: Micromolar BPA inhibits cell proliferation by elevating oxidative stress while nanomolar BPA stimulates cell proliferation by promoting energy metabolism.