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The development of synthetic biology has greatly promoted the construction of microbial cell factories, providing an important strategy for green and efficient chemical production. However, the bottleneck of poor tolerance to harsh industrial environments has become the key factor hampering the productivity of microbial cells. Adaptive evolution is an important method to domesticate microorganisms for a certain period by applying targeted selection pressure to obtain desired phenotypic or physiological properties that are adapted to a specific environment. Recently, with the development of technologies such as microfluidics, biosensors, and omics analysis, adaptive evolution has laid the foundation for efficient productivity of microbial cell factories. Herein, we discuss the key technologies of adaptive evolution and their important applications in improvement of environmental tolerance and production efficiency of microbial cell factories. Moreover, we looked forward to the prospects of adaptive evolution to realize industrial production by microbial cell factories.
Subject(s)
Metabolic Engineering , Industrial Microbiology/methods , Synthetic Biology , Environment , IndustryABSTRACT
Unnatural amino acids are widely used in medicine, pesticide, material, and other industries and the green and efficient synthesis has attracted a lot of attention. In recent years, with the rapid development of synthetic biology, microbial cell factories have become a promising means for biosynthesis of unnatural amino acids. This study reviewed the construction and application of microbial cell factories for unnatural amino acid, including the synthetic pathway reconstruction, design/modification of key enzymes and their coordinated regulation with precursors, blocking of competitive alternative pathways, and construction of cofactor circulation systems. Meanwhile, on the basis of the new principles for designing the microbial cell factories, new biosynthetic pathways adapted to cells and the production environment, as well as new biomanufacturing system established based on cell adaptive evolution and intelligent fermentation regulation, we looked forward to the further construction and application of microbial cell factories for industrial bio-production.
Subject(s)
Amino Acids/genetics , Biosynthetic Pathways , Fermentation , Metabolic Engineering , Synthetic BiologyABSTRACT
Objective To analyze the current research status and problem of ICU visiting before patient transfer in.To supply the reference for the future research in the field. Methods China National Knowledge Infrastructure,Wanfang database and VIP database were searched for literatures on the field. Note Express and Excel 2007 were used to statistical analysis the tendency of the literature publication trend, distribution,region, article type and research topic. Results Totally 86 articles were retrieved. The first was published in 2004,the related articles increased gradually yearly.18 articles were published in core journals and 16 kinds of nursing journals.There were 6 funds-supported articles,3 degree papers. The top three provinces where the first author came from were Jiangsu,Hubei and Shanghai.The primary study types(74.42%) were experimental study and quasi-experimental study. The primary study topic (90.7%)were intervention comparing and problem resolving. Conclusions Research on ICU pre-visiting is focused by the domestic researchers.However,the object of the pre-visiting,visiting content and form should be improved. The tool of visiting should be structured. The research method and topic should be increased.
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Objective To investigate the relationship between Serum BNP and heart failure in patients un-dergoing maintenance peritoneal dialysis ( MPD) .Methods 80 uremia patients who underwent MPD and 40 healthy volunteers were enrolled in the study.In the morning of treatment, we assessed their cardiac function according to in-terrogation, physical examination, chest X-ray and echocardiography while detecting BNP, Scr, BUN levels in the fasting venous serum of upper extremity.Results 80 MPD patients were divided into 2 groups:a heart failure group (Group A, n=42) and a normal cardiac function group (Group B, n=38).40 healthy volunteers served as a con-trol group ( Group C ) .There were no significant differences in age, weight and sex ratio among 3 groups ( P>0.05).The time period of maintenance peritoneal dialysis in Group A and B was similar (P>0.05).Compared with Group C, the levels of Serum BNP, Scr and BUN were significantly higher in Group A and B( P0.05) .The level of Serum BNP was signifi-cantly higher in Group A than that in Group B (P<0.05).Conclusion The level of Serum BNP may be closely re-lated to the cardiac function and it may be used as a predictor for heart failure in MPD patients.
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Objective To investigate sedation of dexmedetomidine versus midazolam on me-chanically ventilated patients.Methods Seventy-six mechanically ventilated patients were randomly divided into midazolam group (group M)and dexmedetomidine group (group D).The loading dose and maintenance dose of midazolam was 0.06 mg/kg and 0.04-0.2 mg·kg-1 ·h-1 ,and 1 μg/kg and 0.2-0.7 μg·kg-1 ·h-1 for dexmedetomidine.The drug dose was adjusted according to Ramsay score scale.Time when Ramsay reach 2-4 score,the length of ICU stay,mechanical ventilation time,drug adverse reactions,the levels of inflammation factors were recorded and compared between two groups.Results The length of ICU stay and arousing time in group D was significantly lower than that of group M (P <0.05).The levels of TNF-α,hs-CRP in group D were lower after 24 hr treat-ment than that of group M(P <0.05).The levels of hs-CRP in group D were lower after 48 hr treat-ment than that of group M (P <0.01).Conclusion Dexmedetomidine treatment reduced the lengh of ICU stay and levels of inflammatory factors of mechanical ventilated patients.
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ObjectiveTo evaluate the improvement on test performance of UniCel DxH 800 automated hematology analyzer for complete blood count (CBC) by detecting its performance indicators and comparing the differences of the results with LH 750 hematology analyzer and ADVIA 2120 hematology analyzer.MethodsThe precision,carryover and linearity of UniCel DxH 800 in measurement of CBC were evaluated by using fresh blood samples and instrument quality control of products.To evaluate the accuracy of leukocyte differential count and reticulocyte count with the microscopic method as the “gold standard”.To calculate the bias and correlation between the results measured by LH 750,ADVIA 2120 and UniCel DxH 800 hematology analyzers and compare these three instruments on the validity of the alarm in abnormal cells.ResultsIntra-precision:The coefficient of variation (CV) of the results of RBC,Hb and MCV were less than 0.5％,the CV of WBC and PLT results were less than 1.5％.Inter-precision:the CV of the parameters above were less than 2.5％.The carryover rate of WBC,RBC,Hb,MCV and PLT were less than 0.51％.In the concentration range covered by clinical samples,the correlation coefficients between the measured values and theoretical value in testing WBC,RBC,Hb and PLT were greater than 0.999 ( P ＜0.01 ).The measurement results of WBC,RBC,Hb,MCV and PLT hy UniCel DxH 800,ADV1A 2120 and LH 750 hematology analyzers have good correlation (r ＞ 0.973,P ＜ 0.01 ).Correlation of reticulocyte count between the UniCel DxH 800 hematology analyzer and microscolpic method was significant (r =0.920,P ＜0.01 ).Correlation of leukocyte differential count about the grauulocytes, lymphocytes and eosinophils between the UniCel DxH 800 hematology analyzer and microscopic method was good (r =0.914,0.900 and 0.725,P ＜0.01 ),followed by monocytes ( r =0.612,P ＜0.01 ),which were better than the LH 750 with similar detection principle.The UniCel DxH 800 hematology analyzer demonstrated higher sensitivity (96.6％ ) for the alarm of abnormal cells and achieved a lower false-negative rate (2.5％ ).Meanwhile,the sensitivity of the neutrophil nuclei left shift was higher (90.5％ ) and the false-negative rate (5.0％) was lower.ConclusionsThe UniCel DxH 800 hematology analyzer for complete blood count shows advantages of high precision,low carryover rate and wide linear range.The results detected by the UniCel DxH 800 hematology analyzer have good correlation with the LH 750 and ADVIA 2120.
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OBJECTIVE To explore the clinical characteristics of hospital infection in diabetic nephropathy(DN). METHODS To retrospectively analyze the incidence rate of hospital infection,the infection sites,pathogenic bacteria,and predisposing factors in 348 cases with diabetic nephropathy,and to compare the index above with the homeochronous 466 diabetic patients without DN. RESULTS Sixty two cases occurred hospital infection from 348 cases with DN,the infection rate was 17.82%,the infection sites were most frequently in respiratory tract(37.10%),then urinary tract(24.19%) and digestive tract(19.35%),the major predisposing factors were out of control of blood glucose,renal sufficiency,advanced age,and longer stay in hospital. CONCLUSIONS The incidence rate of hospital infection is higher,the valid measures to control the hospital infection are to control the blood glucose effectively,to improve the renal function and timely to use the method of anti-infection with forcefulness.
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OBJECTIVE: To explore the therapeutic effect of prostaglandin E1 lipid drug-loaded microcapsules(Lipo PGE1) on the earlier diabetic nephropathy (DN). METHODS: 72 cases with early DN were randomly divided into treatment group and control group. The control group were assigned to receive routine hypoglycemic agent,blood pressure controlling, and symptomatic treatment, while the treatment group were given another drip infusion of Lipo PGE1 20ug plus NS100ml q.d besides the routine therapy as in the control group. Both groups received 3 weeks’ course of treatment. The changes of urinary albumin excretion rate(UAER), urinary transferrin(TRF), urinary microglobulin(?1MG)and so on in the 24h urine of the 2 groups before and after treatment were observed.RESULTS: There was great decrease in UAER, TRF and ?1MG in the 24h urine in the treatment group after treatment(P
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Objective To expolre the clinical characteristic of hospital acquired acute renal failure(HA-ARF).Methods To retrospectively analyse the clinical datas of 103 patients who were suffered from acute renal failure in the duration of hospital stay within 5 years,which was compared with the homeochronous community-acquired acute renal failure(CA-ARF).Results In the 103 cases of HA-ARF,the incidence rate was 32.04% in the major age range from 60 to 74 years old,infection was the most important factor(33.01%),then other factors were cardial and cerebrovascular diseases(17.48%),acute hypovolemia(14.56%) and operation(9.71%);The complicating other organ nonfunction(34.95%),and the mortality rate was 39.80%,all the factors in HA-ARF were higher than that in CA-ARF.Conclusion The main factors of origin in HA-ARF are infection,cardial and cerebrovascular disease,acute hypovolemia and operation.The mortality rate of this disease is higher.Etilogical treatment promptly and dialysis regimen are the main means to rescue these patients.
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Objective To study the therapeutic effects of mycophenolate mofetil(MMF) in the treatment of refractory idiopathic thrombocytopenic purpura(ITP).Methods 16 refractory ITP patients were treated with MMF (1.0～1.5g/d),which were given in divided doses for three months as one course;the patients with significant therapeutic effect were given the dose for another three months and reduced by degree.Results Very effective results were obtained in 4 cases,striking improvement in 7,partial response in 1 and no response in 4.The total efficacy was 68.75%.The main side effect was observed as light digestive malaise.Conclusion MMF has striking therapeutic effect in treating refractory ITP with little side effect and can be used as an effective way of treatment.