Improvement of Curvulamine Production by Precursors Co-addition Strategy in Liquid Culture of Marine-Derived Fungus Curvularia sp. IFB-Z10.

Curvulamine, a novel scaffold alkaloid with remarkable selective antibacterial activity, is produced by marine fungus Curvularia sp. IFB-Z10. However, its deep pharmaceutical research and application are severely restricted by the low yield, which needs to be solved urgently. The purpose of this study was to improve curvulamine production via precursors co-addition strategy and further reveal the regulation mechanism. In this work, the optimal precursors co-addition conditions were firstly obtained, and curvulamine production achieved 166.74 mg/L with the supply of 250 mg/L alanine and 200 mg/L proline at 60 h, which was 4.08 times that of control. It was observed that under alanine and proline stimulation, fungus exhibited the morphology of a small-diameter compact pellet. Furthermore, the organic acid levels in central carbon metabolism (CCM) were declined with precursors supplement. Besides, precursors also induced the critical biosynthetic gene transcriptions. The above findings collectively promoted curvulamine synthesis. Finally, Curvularia sp. IFB-Z10 fermentation process was successfully established by feeding alanine and proline at 0.021 g/L/h and 0.017 g/L/h rate from 60 to 72 h, and curvulamine production reached 133.58 mg/L in a 5-L bioreactor. The information acquired would facilitate the enhancement of curvulamine yield in submerged fermentation and the research on synthesis regulation of other alkaloids.

Ammonium Acetate Supplement Strategy for Enhancement of Chaetominine Production in Liquid Culture of Marine-Derived Aspergillus fumigatus CY018.

Pharmacological research on (CHA), a marine-derived quinazolinone alkaloid with significant cytotoxic activity, is restricted by low yields and is a problem that needs to be settled urgently. In this work, the selection of additional nitrogen sources and the optimization of additional concentrations and longer fermentation times using ammonium acetate, were investigated. CHA production was optimized to 62.1 mg/l with the addition of 50 mM ammonium acetate at 120 h of the fermentation in the shaker flask. This feeding strategy significantly increased 3- deoxy-arabino-heptulosonate-7-phosphate synthase activity and transcript levels of critical genes (laeA, dahp and trpC) in the shikimate pathway compared with the non-treatment group. In addition, the selection of the feeding rate (0.01 and 0.03 g/l/h) was investigated in a 5-L bioreactor. As a result, CHA production was increased by 57.9 mg/l with a 0.01 g/l/h ammonium acetate feeding rate. This work shows that the strategy of ammonium acetate supplementation had an effective role in improving CHA production by Aspergillus fumigatus CY018. It also shows that this strategy could serve as an important example of large-scale fermentation of a marine fungus in submerged culture.

Dissolved oxygen control strategy for improvement of TL1-1 production in submerged fermentation by Daldinia eschscholzii.

BACKGROUND: 2,3-Dihydro-5-hydroxy-2-methylchromen-4-one (TL1-1) is a phenolic compound with significant anti-fungal and anti-cancer activities produced by Daldinia eschscholzii (D. eschscholzii). However, studies have rarely been reported on the fermentation process of D. eschscholzii due to the urgent demand for its pharmaceutical researches and applications. RESULTS: In this work, the optimal fermentation medium for improved TL1-1 yield was first obtained in a shake flask. As the fermentation process was scaling up, the marked effects of dissolved oxygen (DO) on cell growth and TL1-1 biosynthesis were observed and confirmed. Controlling a suitable DO level by the adjustment of agitation speed and aeration rate remarkably enhanced TL1-1 production in a lab-scale bioreactor. Moreover, the fermentation of D. eschscholzii was successfully applied in 500-L bioreactor, and TL1-1 production has achieved 873.63 mg/L, approximately 15.4-fold than its initial production (53.27 mg/L). CONCLUSIONS: Dissolved oxygen control strategy for enhancing TL1-1 production was first proposed. Furthermore, control of the appropriate DO level has successfully performed for improving TL1-1 yield and scale-up of D. eschscholzii fermentation process.

Successful tubes treatment of esophageal fistula / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>AIM</b>To discuss the merits of "tubes treatment" for esophageal fistula (EF).</p><p><b>METHODS</b>A 66-year-old female who suffered from a bronchoesophageal and esophagothoratic fistula underwent a successful "three tubes treatment" (close chest drainage, negative pressure suction at the leak, and nasojejunal feeding tube), combination of antibiotics, antacid drugs and nutritional support. Another 55-year-old male patient developed an esophagopleural fistula (EPF) after esophageal carcinoma operation. He too was treated conservatively with the three tubes strategy as mentioned above towards a favorable outcome.</p><p><b>RESULTS</b>The two patients recovered with the tubes treatment, felt well and became able to eat and drink, presenting no complaint.</p><p><b>CONCLUSION</b>Tubes treatment is an effective basic way for EF. It may be an alternative treatment option.</p>

Investigation on medical cost of 72 patients with panic disorder / 中国基层医药

Objective To investigate the medical cost of 72 patients with panic disorder and efficacy of paroxetine(SSRIs)in the treatment.Methods The course,medical cost,types and times of main examination of all 72 patients were reviewed and analyzed.The effect of paroxetine on the patients was studied in terms of anxiety and depression scale.Results The 72 patients had long course,high medical cost and received many unnecessary medical examinations.Paroxerine was effective on patients with panic disorder in light of anxiety and depression scale.Con- clusion Patients with panic disorder had long course and spent much unnecessany money before final diagnosis. Paroxetine was useful and safe in the treatment of panic disorder.

An epidemiological survey of alcoholic liver disease in Zhejiang province / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To describe the brief survey of alcohol intake and the incidence of alcohol liver disease in Zhejiang province.</p><p><b>METHODS</b>18,237 requested persons aged over 18 years were selected by multi-stage stratified cluster sampling in Zhejiang province. Questionnaire about alcohol consumption, hepatic ultrasonic scan and detection of hepatic enzymes and markers of HBV and HCV were carried out. Daily alcohol intake more than 40g (including equal to 40g/d) was essential for the diagnosis of alcoholic liver disease.</p><p><b>RESULTS</b>Among the 18,237 persons (male 12,042, female 6195), the average daily alcohol intake was (17.7 +/- 27.2) g. The incidence of alcoholic liver disease in Zhejiang province was 4.34% (male 6.36%, female 0.36%) in the whole population. Four subtypes were separated as alcoholic cirrhosis, alcoholic fat liver, alcoholic hepatitis and mild alcoholic injury in liver with the corresponding incidence of 0.68%, 0.94%, 1.51% and 1.21% separately.</p><p><b>CONCLUSION</b>Alcoholic liver disease is found to be a common disease in Zhejiang province, indicating an urgent need for the public education on alcohol abuse and the treatment on related health problems</p>