The fungal bioluminescence pathway (FBP) is a metabolic pathway responsible for the generation of bioluminescence derived from fungi. This pathway utilizes caffeic acid as the substrate, generating a high-energy intermediate, and the decomposition of which yields green fluorescence with a wavelength of approximately 520 nm. The FBP is evolutionally conserved in luminescent fungal groups. Unlike other bioluminescent systems, the FBP is particularly suitable for engineering applications in eukaryotic organisms, especially in plants. Currently, metabolically engineered luminescent plants are able to emit visible light to illuminate its surroundings, which can be visualized clearly in the dark. The fungal bioluminescent system could be explored in various applications in molecular biology, biosensors and glowing ornamental plants, and even green lighting along city streets.
Luminescence ; Light ; Fluorescence ; Eukaryota ; Green Light

ObjectiveTo investigate the therapeutic effect and mechanism of coptisine on chronic atrophic gastritis （CAG） in rats based on the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodA CAG rat model was induced by multiple factors， including sodium salicylate， N-methyl-N′-nitro-N-nitrosoguanidine （MNNG）， and irregular feeding. The successfully modeled rats were randomly divided into the model group， folic acid group， and high- and low-dose coptisine groups. The high- and low-dose coptisine groups were given coptisine （50， 10 mg·kg^-1， respectively）， and the folic acid group was given folic acid at 2 mg·kg^-1 for 60 days. The pathological changes were detected by hematoxylin-eosin （HE） staining. The ultrastructure of gastric mucosal cells was observed by electron microscopy. Serum pepsinogen Ⅰ （PGⅠ）， pepsinogen Ⅱ （PGⅡ）， and PGⅠ/PGⅡ ratio （PGR） were detected by immunoturbidimetry. Serum gastrin-17 （G-17） level was detected by radioimmunoassay. The content of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in serum of rats was detected by enzyme-linked immunosorbent assay （ELSIA）. Western blot analysis was used to detect the expression levels of TGF-β₁， PI3K， phosphorylated-Akt （p-Akt）， mTOR， and phosphatase and tensin homolog deleted on chromosome 10 （PTEN） in gastric mucosa. The mRNA levels of TGF-β₁， PI3K， Akt， mTOR， PTEN， microtubule-associated protein light chain 3Ⅱ （LC3Ⅱ）， and Beclin-1 were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group， the model group showed atrophy and reduced number of intrinsic glands in the gastric mucosal tissues， as well as inflammatory cell infiltration. The ultrastructure of gastric mucosal cells in the model group displayed nuclear condensation， reduced and swollen mitochondria， and abnormal structure. The serum levels of G-17， PGⅠ， PGR， and the protein and mRNA levels of PTEN in gastric tissues were significantly lower in the model group （P<0.01）， while serum levels of IL-6， IL-1β， TNF-α， and the protein and mRNA levels of TGF-β₁， PI3K， Akt， and mTOR in gastric tissues were significantly higher （P<0.01）. Compared with the model group， various drug intervention groups showed different degrees of improvement in pathological damage and gastric mucosal cell ultrastructure， significantly increased serum levels of G-17， PGⅠ， and PGR （P<0.05，P<0.01）， and significantly decreased levels of IL-6， IL-1β， and TNF-α （P<0.05，P<0.01）. The high-dose coptisine group significantly downregulated the protein and mRNA levels of TGF-β₁， PI3K， Akt， and mTOR （P<0.05，P<0.01）. ConclusionBerberine has a therapeutic effect on CAG in rats， possibly exerting a protective effect on gastric mucosa by inhibiting inflammation and blocking the PI3K/Akt/mTOR signaling pathway.

Objective:To analyze hip joint movement during the swing phase of the strides of stroke survivors with hemiplegia and foot drop.Methods:Thirty stroke survivors with hemiplegia and foot drop formed the observation group, while thirty matched healthy counterparts were the control group. A three-dimensional gait analysis system was used to compare the hip and ankle joint kinematics on the hemiplegic side of the observation group members with those on the corresponding side of a matched control. Pearson correlation related the maximum plantar flexion angle of the ankle and hip joints in the observation group.Results:Compared with the control group, there was a significant increase in the maximum abduction and external rotation of the hip joint during the swing phase, but a significant decrease in the maximum extension, flexion, adduction, internal rotation. The range of motion of the hip joint in the sagittal, frontal and horizontal planes was significantly smaller, as was the maximum dorsiflexion and sagittal range of motion of the ankle joint. The maximum plantar flexion angle of the ankle was positively correlated with the hip joint′s maximum flexion, maximum external rotation and sagittal joint motion, but negatively correlated with the hip′s horizontal motion.Conclusion:In stroke survivors with hemiplegia and ptosis, significant changes are observed in the three-dimensional motion during the swing phase of a stride. The mode of hip joint compensation changes depending on the severity of the foot drop.

OBJECT IVE To study the effects of ergosterol peroxide derivatives EP-3P on the proliferation ，migration and invasion of human tripe negative breast cancer cell MDA-MB- 231，and to provide reference for the development of breast cancer related drugs. METHODS MTT assay was adopted to detect the proliferation of MDA-MB- 231 cells after treated with 0（blank control），1.25，2.5，5，10，20，40 μmol/L EP-3P for 24，48 and 72 h. Wound healing assay and Transwell chamber method were adopted to detect the migration and invasion ability of MDA-MB- 231 cells after treated with 0（blank control ），5，10，20 EP-3P for 24 h. The apoptosis and cell cycle distribution were detected by flow cytometry. Western blot assay was used to detect the expressions of B-cell lympho ma-2（Bcl-2），Bcl-2 associated X protein （Bax），caspase-3，cleaved-caspase-3，cytochrome C （Cyt-C），matrix metalloproteinase- 2（MMP-2）and MMP- 9. RESULTS Compared with blank control group ，2.5，5，10，20，40 μmol/L EP-3P could significantly increase the inhibitory rate of cell proliferation （P＜0.05 or P＜0.01）in a dose and time- dependent manner. After 24 h treatment of EP- 3P（10，20 μmol/L），the rate of cell migration and the number of invasive cells were decreased significantly （P＜0.01），and cell was arrested at G 2/M stage （P＜0.05 or P＜0.01）；the apoptotic rate was increased significantly （P＜0.05）；the protein expressions of Bax ，Cyt-C and cleaved-caspase- 3 were upregulated significantly ， while those of Bcl- 2，caspase-3，MMP-2 and MMP- 9 were downregulated significantly （P＜0.01）. CONCLUSIONS EP-3P can inhibit the proliferation ，migration and invasion of human tripe negative breast cancer cells MDA-MB- 231 through mitochondrial mediated endogenous caspase pathway ，and induce the apoptosis of cells .

Background Prolonged exposure to vibration can cause vascular endothelial injury, and inflammatory response plays an important role in vascular endothelial injury. Studies have shown that long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) is involved in regulating the expression of inflammatory injury of endothelial cells. Objective To investigate the effects of vibration on the secretion of inflammatory factors and the expression of IncRNA MEG3 by vascular endothelial cells in vitro. Methods Human umbilical vein endothelial cells (HUVEC) were divided into two categories: vibration and control. The vibration exposure included 63 Hz (6.76 m·s⁻²), 200 Hz (5.08 m·s⁻²), and 250 Hz (4.56 m·s⁻²) frequency bands, and 1 and 2 d exposure time with 1 to 4 h of daily vibration. The control treatment was the same as the vibration category except that they were not exposed to vibration. CCK-8 was used to detect the effects of different vibration frequencies and time on the viability of HUVEC. The expression levels of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), interleukin-4 (IL-4), and interleukin-10 (IL-10) in the cells and supernatants were detected by enzyme-linked immunosorbent assay. The expression levels of IncRNA MEG3 were detected by real-time fluorescence quantitative PCR. Results Compared with the cells with the control treatment, the cell viability of the 1-day exposure group increased after 1.5 h and 3 h of vibration at 63 Hz, while decreased after 2 h and 2.5 h; the cell viability of the 2-day exposure group increased at the frequency of 63 Hz for 1.5 h, but decreased at 2 h and 2.5 h. At the frequency of 200 Hz, the cell viability of the 1-day exposure group increased at 2 h and 4 h, but decreased at 2.5 h and 3 h; the cell viability of the 2-day exposure group increased at 1.5 h and decreased at 2.5 h. For the vibration exposure at frequency of 250 Hz, the cell viability of the 1-day exposure group increased at 1.5 h and 2.5 h, but decreased at 3 h; of the 2-day exposure group, the cell viability increased at 1.5 h and decreased at 3 h. For the exposure settings of 63 and 200 Hz vibration for 2.5 h and 250 Hz vibration for 3 h, and with the control treatment as reference, the expression levels of TNF-α, IL-8, IL-4, and IL-10 in cells and supernatants were increased in the 1 d and 2 d exposures; the expression level of lncRNA MEG3 decreased in the 1 d exposure group; however, for the 2 d exposure, the expression level of lncRNA MEG3 decreased only in the 63 Hz vibration exposure. All of these results were statistically significant (P<0.05). Conclusion Vibration could induce an increase in the levels of inflammatory factors TNF-α, IL-8, IL-4, and IL-10 and a decrease in the expression level of lncRNA MEG3 in vascular endothelial cells in vitro.

Objective:To observe the clearance strategies of hemiplegic stroke survivors with foot drop.Methods:Thirty hemiplegic stroke survivors with foot drop formed the observation group and 30 healthy counterparts constituted the control group. A three-dimensional motion capture system was used to observe and compare the minimum toe clearance (MTC) and its variability between the two groups to draw the motion trajectory of the toe in the swing phase of their gaits. The gait parameters were correlated with the toe clearance.Results:The average MTC of the observation group subjects on both the hemiplegic and non-hemiplegic side (12.01±3.36 and 22.38±5.51mm) was significantly smaller than the control group′s averages. The variability of their MTCs on both sides was also significantly greater. Clearance on the hemiplegic side was significantly less and its variability was significantly greater. Among the observation group, MTC on the hemiplegic side was positively correlated with walking speed, step length, swing phase percentage, maximum angle of hip extension, maximum angle of knee flexion, maximum angle of ankle dorsiflexion, and the range of motion of the knee and ankle joints.Conclusions:Hemiplegic stroke survivors with foot drop walk unstably with little toe clearance. It is necessary to intervene at the hip, knee and ankle to improve their obstacle clearance.

ObjectiveTo explore the mechanism of Xianglian Huazhuo prescription in the treatment of chronic atrophic gastritis （CAG） based on network pharmacology and animal experiments，so as to provide scientific basis for clinical application. MethodThe possible targets and pathways of Xianglian Huazhuo prescription in the treatment of CAG were obtained based on the prediction of network pharmacology. The CAG rat model was induced by sodium salicylate，N-methyl-N'-nitro-N-nitrosoguanidine （MNNG） and hunger and satiety disorder. Then the CAG rats were treated with Xianglian Huazhuo prescription and morodan for 60 days. After administration，the rats were sacrificed，and the content of interleukin-6 （IL-6），tumor necrosis factor-α （TNF-α），interleukin-1β （IL-1β） and vascular endothelial growth factor （VEGF） in serum was determined by enzyme linked immunosorbent assay（ELISA）. In addition， the protein expression of Bad and Bcl-2 in gastric mucosa was detected by immunohistochemistry （IHC）. ResultA total of 241 active components of Xianglian Huazhuo prescription and 53 core targets were obtained. Xianglian Huazhuo prescription affected multiple biological processes，such as cell proliferation and apoptosis，inflammatory reaction，regulation of DNA metabolism，and cell response to redox，as well as phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt），TNF，mitogen-activated protein kinase （MAPK），cancer and cancer-related signaling pathways. The animal model verification showed that Xianglian Huazhuo prescription lowered the levels of IL-6，TNF-α，IL-1β and VEGF in serum of CAG rats，and reduced the protein expression of Bad and Bcl-2 in gastric tissue. ConclusionXianglian Huazhuo prescription could regulate PI3K/Akt signal pathway and improve gastric mucosal injury in CAG by participating in biological processes such as cell proliferation，apoptosis and inflammation.

Objective:To investigate the effects of hyperuricemia on the prognosis of IgA nephropathy (IgAN) using propensity score matching (PSM) method.Methods:IgAN patients proven by biopsy were included. PSM was used to match patients. Kaplan-Meier method was used for survival analysis, and Cox regression analysis was used to analyze the effects of hyperuricemia on IgAN prognosis. Primary outcome events were defined as death, or end-stage renal disease (dialysis, transplantation), or a decrease in estimated glomerular filtration rate (eGFR) greater than 40%. Renal outcome was defined as end-stage renal disease (dialysis, transplantation), or a decrease in eGFR greater than 40%.Results:A total of 1 454 IgAN patients were included in this study, including 850 females and 604 males. Uric acid level was (368.26±92.87) μmol/L in the males, and (277.23±92.71) μmol/L in the females. The median follow-up time was 85.00(56.10, 106.33) months. During the follow-up period, a total of 134 patients reached the primary outcome events, including 5 deaths, 24 dialysis patients, 5 kidney transplant patients, and 100 patients with eGFR decreased by more than 40%. After 1∶1 matching, 131 males and 159 females in the hyperuricemia group were successfully matched with 131 males and 159 females in the normal uric acid group, and there was no significant statistical difference in each parameter in baseline between the hyperuricemia group and normal uric acid group after matching. Kaplan-Meier survival analysis showed that either before or after matching, the incidence of primary outcome events in male or female patients with hyperuricemia was higher than those with normal uric acid, but there was no statistically significant difference in incidence of primary outcome events between female hyperuricemia group and female normal uric acid group after matching (Log-rank test, χ2=3.586, P=0.058). Cox proportional hazard regression model showed that, in the pre-match fully adjusted model, the hazard ratio ( HR) of entering primary outcome events was 2.29-fold (95% CI 1.27-4.11, P=0.006) for men with hyperuricemia and 1.85-fold (95% CI 1.01-3.37, P=0.045) for women with hyperuricemia compared with those with normal uric acid. In the post-match fully adjusted model, the HR of entering primary outcome events was 2.41-fold (95% CI 1.18-4.93, P=0.016) for men with hyperuricemia and 1.83-fold (95% CI 0.91-3.67, P=0.091) for women with hyperuricemia compared with those with normal uric acid. In the pre-match fully adjusted model, the HR of entering renal outcome events was 2.68-fold (95% CI 1.47-4.88, P=0.001) for men with hyperuricemia and 1.81-fold (95% CI 0.99-3.33, P=0.056) for women with hyperuricemia compared with those with normal uric acid. In the post-match fully adjusted model, the HR of entering renal outcome events was 2.89-fold (95% CI 1.36-6.15, P=0.006) for men with hyperuricemia and 1.81-fold (95% CI 0.88-3.72, P=0.106) for women with hyperuricemia compared with those with normal uric acid. Conclusion:Hyperuricemia may be associated with IgAN progression, and it has a more significant effect on male IgAN patients.

CircRNA is a new endogenous non-coding RNA(ncRNA ) and a member of the competitive endogenous RNA(ceRNA) family. Some researches have found that circRNA exists widely in organisms and interacts with miRNA, which has certain influence on the occurrence and development of liver diseases. This article reviews the research progress of circRNA and its biological functions, as well as the relationship between circRNA and liver disease, in order to expound the role of circRNA in liver diseases and guide clinical practice better.

Objective:To establish and evaluate acute hepatic sinusoidal obstruction syndrome (HSOS) mouse models induced by three pyrrolidine alkaloids (PAs) including monocrotaline (MCT), retrorsine (RTS) and senecionine (SEN).Methods:Forty-eight male C57 mice were divided into four groups, control group, MCT group, RTS group and SEN group, with 12 mice in each group, which were gavaged once with phosphate buffer saline (300 μL), MCT solution (800 mg/kg), RTS solution (100 mg/kg) and SEN solution (100 mg/kg), respectively. At 24 hours after gavage, the number of mortality and success modeling, liver function, and pathological changes of liver of four groups of mice were analyzed. One way analysis of variance, Bonferroni test and Chi-square test were used for statistical analysis.Results:At 24 hours after gavage, the number of dead mice of MCT group, RTS group and SEN group was zero, nine and zero, respectively; and the number of survival successfully modeled mice was nine, three and six, respectively; the difference of mortality among three groups was statistically significant ( χ2=21.734, P<0.05), and the difference of the number of success modeling was not statistically significant ( χ2=2.836, P>0.05). The alanine aminotransferase (ALT) levels of MCT group, RTS group and SEN group were (111.72±37.62), (562.97±242.42) and (3 891.40±1 009.44) U/L, respectively; aspartate transaminase (AST) levels were (156.96±64.95), (331.22±120.83) and (2 107.55±532.80) U/L, respectively; and total bilirubin (TBil) levels were (41.66±10.42), (79.43±18.45) and (120.80±17.44) μmol/L, respectively, which were all higher than those of the control group ((31.40±10.98) U/L, (34.66±13.00) U/L and (16.91±2.89) μmol/L, respectively); and the differences were statistically significant (Bonferroni test, all P<0.008 3). There were statistically significant differences in ALT and AST levels between MCT group and RTS group (Bonferroni test, both P<0.008 3), while there was no statistically significant difference in TBil level between two groups ( P>0.008 3). There was statistically significant difference in TBil level between MCT group and SEN group (Bonferroni test, P=0.002), however there were no statistically significant differences in ALT and AST levels between two groups (both P>0.008 3). There were statistically significant differences in ALT, AST and TBil levels between RTS group and SEN group (Bonferroni test, all P<0.008 3). The mouse liver tissues of all three groups showed coagulative necrosis of hepatocytes, subendothelial hemorrhage of central vein, the dilation of hepatic sinusoids, erythrocyte clogging in the space of disse, and destruction of normal lobular structure. In MCT and RTS groups, the main damages were hepatocyte necrosis, sinusoidal dilatation and congestion in zone 3 of the liver acinus, while in SEN group, which were hepatocyte necrosis and sinusoidal congestion in zone 1 and 2 of the liver acinus. The histological changes of mouse liver tissues of MCT group were moderate to severe, and those of RTS group and SEN group were all severe. Conclusions:Acute HSOS mouse models induced by three kinds of PA including MCT, RTS and SEN are successfully established, of which MCT is the most suifable choice.