Objective:To research and design a negative pressure environment that can be applied in container type of biological isolation shelter,so as to meet the stable negative pressure environment and dynamic intelligent regulation of pressure difference in the container during multimodal transportation,especially under air freight conditions.Methods:The design specifications and research achievements of pressure differences of negative pressure isolation equipment for infectious diseases at home and abroad were comprehensively analyzed.And then,one kind of power-distributed ventilation system without air duct was designed to achieve.The preseted pressure redundancy,real-time monitoring of sensors and dynamic follow-up of pressure were used to realize stable and intelligent regulation of negative pressure within the container during air freight.Results:After testing,the pressure differences of each region of the"three regions and two channels"included clean region,buffer region,contamination region,medical staff passage and patient passage within container type of biological isolation shelter under the negative pressure environment could meet the preseted requirements.The values of pressure differences at the outside of room of clean region,the toilet of clean region,the toilet of clean region of the second dressing room of the buffer region,the contamination region of the first dressing room of the buffer region,the toilet of contamination region and the outside of the room of contamination region were respectively 34.2,38.8,-8.0,-31.7,-15.1 and-44.6.The conditions of the pressure differences within each region of container,which dynamically met the requirements of Biosafety Level-Ⅲ(BSL-3)laboratory,were tested through the sensors,and intelligent display and control equipment that deployed inside of container.Conclusion:The stable negative pressure environment and intelligent regulation for pressure difference in each region of the container can take container to have more high biosafety characteristics,which can effectively ensure the safe transportation of whole region for patients with severe infectious diseases,and the transport and treatment under air freight condition.

Yarrowia lipolytica is a non-conventional yeast with unique physiological and metabolic characteristics. It is suitable for production of various products due to its natural ability to utilize a variety of inexpensive carbon sources, excellent tolerance to low pH, and strong ability to secrete metabolites. Currently, Y. lipolytica has been demonstrated to produce a wide range of carboxylic acids with high efficiency. This article summarized the progress in engineering Y. lipolytica to produce various carboxylic acids by using metabolic engineering and synthetic biology approaches. The current bottlenecks and solutions for high-level production of carboxylic acids by engineered Y. lipolytica were also discussed, with the aim to provide useful information for relevant studies in this field.
Carboxylic Acids/metabolism* ; Metabolic Engineering ; Synthetic Biology ; Yarrowia/metabolism*

Higher alcohols are one of the main by-products of Saccharomyces cerevisiae in brewing. High concentration of higher alcohols in alcoholic beverages easily causes headache, thirst and other symptoms after drinking. It is also the main reason for chronic drunkenness and difficulty in sobering up after intoxication. The main objective of this review is to present an overview of the flavor characteristics and metabolic pathways of higher alcohols as well as the application of mutagenesis breeding techniques in the regulation of higher alcohol metabolism in S. cerevisiae. In particular, we review the application of metabolic engineering technology in genetic modification of amino transferase, α-keto acid metabolism, acetate metabolism and carbon-nitrogen metabolism. Moreover, key challenges and future perspectives of realizing optimization of higher alcohols metabolism are discussed. This review is intended to provide a comprehensive understanding of metabolic regulation system of higher alcohols in S. cerevisiae and to provide insights into the rational development of the excellent industrial S. cerevisiae strains producing higher alcohols.
Alcoholic Beverages ; Alcohols/analysis* ; Fermentation ; Saccharomyces cerevisiae/metabolism* ; Saccharomyces cerevisiae Proteins/metabolism*

Objective:To explore the application prospect of "education cloud platform + dual track" teaching in continuing medical education of thoracic surgery.Methods:A total of 100 trainees who participated in continuing medical education in thoracic surgery department in Air Force Medical University were randomly divided into experimental group and control group, with 50 students in each group. The experimental group adopted "education cloud platform + dual-track" teaching, and the control group adopted dual-track teaching. At the end of the study, an examination of theoretical knowledge and practical operation would be conducted; at the same time, an anonymous questionnaire survey would be used to evaluate the satisfaction of the two teaching modes. SPSS 20.0 was used for t test and chi-square test. Results:There was no statistically significant difference between the two groups in basic theoretical performance. The professional theoretical performance [(28.6±3.7) points] and operational theory performance [(34.9±4.7) points] of the experimental group were higher than those of the control group, with significant differences ( P<0.05). The experimental group performed better than the control group in five practical operation assessments: basic operation of thoracoscopy, basic operation of opening and closing the chest, operation of vascular isolation and suture, operation of esophageal anastomosis and operation of tracheal anastomosis, with statistical differences ( P<0.05). The satisfaction with teaching of experimental group was significantly higher than that of the control group ( P<0.05). Conclusion:"Education cloud platform + dual track" teaching can effectively ensure the teaching progress of problem-based learning (PBL) and team-based learning (TBL), improve students' learning effect, and has high promotion and application value.

As a new beer fermentation technology, high temperature and high gravity fermentation has brought many benefits to brewery industry, but there are also a series of problems such as the decrease of yeast flocculation ability at the end of fermentation and the high concentration of higher alcohols. To increase yeast flocculation ability and reduce the production of higher alcohols in high temperature and high gravity fermentation of beer, BAT2 was replaced by the FLO5 expression cassette to obtain the mutant strain S6-BF2. Real-time quantitative PCR showed that the relative transcriptional level of FLO5 in S6-BF2 improved 17.8 times compared with that in S6. The flocculation ability of mutant S6-BF2 heightened by 63% compared to that of the original strain S6, and the concentration of higher alcohols decreased from 175.58 mg/L to 159.58 mg/L in high temperature and high gravity fermentation of beer. Moreover, the activity of mitochondrial branched-chain amino acid transferase was repressed, resulting in the production of higher alcohols of 142.13 mg/L, reduced by 18.4% compared to that of the original strain S6, meanwhile, the flocculation ability of mutant S6-BF2B1 kept unchanged compared to the mutant S6-BF2. The determination result of flavor compounds showed that the higher alcohols/ester ratio in beer was reasonable. This research has suggested an effective strategy for enhancing yeast flocculation ability and decreasing production of higher alcohols in high-temperature and high-gravity brewing.
Beer ; Fermentation ; Hypergravity ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae Proteins ; Temperature ; Transaminases

Xylulose as a metabolic intermediate is the precursor of rare sugars, and its unique pattern of biological activity plays an important role in the fields of food, health, medicine and so on. The aim of this study was to design a new pathway for xylulose synthesis from formaldehyde, which is one of the most simple and basic organic substrate. The pathway was comprised of 3 steps: (1) formaldehyde was converted to glycolaldehyde by benzoylformate decarboxylase mutant BFD-M3 (from Pseudomonas putida); (2) formaldehyde and glycolaldehyde were converted to dihydroxyacetone by BFD-M3 as well; (3) glycolaldehyde and dihydroxyacetone were converted to xylulose by transaldolase mutant TalB-F178Y (from Escherichia coli). By adding formaldehyde (5 g/L), BFD-M3 and TalB-F178Y in one pot, xylulose was produced at a conversion rate of 0.4%. Through optimizing the concentration of formaldehyde, the conversion rate of xylulose was increased to 4.6% (20 g/L formaldehyde), which is 11.5 folds higher than the initial value. In order to further improve the xylulose conversion rate, we employed Scaffold Self-Assembly technique to co-immobilize BFD-M3 and TalB-F178Y. Finally, the xylulose conversion rate reached 14.02%. This study provides a new scheme for the biosynthesis of rare sugars.

Objective To analyze the epidemic characteristics of brucellosis in Nangang District of Harbin City,and to provide a scientific basis for making strategies in prevention and control of the disease.Methods Descriptive epidemiological methods were used,epidemic characteristics (time distribution,regional distribution and population distribution) of the disease in Nangang District of Harbin City in 2006-2015 were studied,and brucellosis cases were reported online through the national epidemic network.Results A total of 105 cases of brucellosis were reported,the average annual incidence rate was 7.84/100 thousand and no death case.The number of cases was the highest in 2014,it was 21 cases,the incidence rate was 1.57/100 thousand;the number of cases was the least in 2010,it was 3 cases,the incidence rate was 0.22/100 thousand;in 2006,the number of cases was 9,the incidence rate was 0.67/100 thousand;in 2015,the number of cases was 17,the incidence rate was 1.27/100 thousand.The incidence of the disease was mainly concentrated in summer and autumn,accounting for 65.71％ (69/105),the number of summer onset was 38,accounting for 36.19％ (38/105);the incidence of the autumn was 31,accounting for 29.52％ (31/105).In 2006-2012,the incidence of the disease was mainly concentrated in Wanggang and Hongqi townships,accounting for 60.00％ (30/50);after 2013,the cases in urban areas were on the rise,Wanggang and Hongqi townships accounted for 34.55％ (19/55).Incidence of male youth was the highest,male and female incidence ratio was 2.18:1.00 (72:33);incidence peak was 30-60 years old,accounting for 60.95％ (64/105);after analyzing the incidence of occupational groups,farmer was the highest,accounting for 43.81％ (46/105).Transmission route was contact with cattle and sheep and lived in the environment cattle and sheep were breed,the number of cases was 34.Conclusions The incidence of brucellosis in Nangang District of Harbin City is rising after 2013.Disease season focus in summer and autumn,occupation focus in farmers,and the scope of the outbreak has been expanded.We should further strengthen publicity and education in disease focus season,improve the awareness of protection,in order to effectively control the epidemic of brucellosis.

The ethical issues are different at different research stages of drug discovery.At the preclinical trial phase,laboratory animals are indispensable.The medical animal ethics committees need to approve and supervise animal testing during the experiment whether it adheres to the principles of animal protection,animal welfare principles and ethicalprinciples.At the phase of clinical trials,the subject of drug is human.The medical ethics committee should take full account of the ethical issues arising from the special medicine,special populations and disease in the process of trial and formulate detailed and feasible clauses,thus to ensure the scientificity of the trial and the rights and interests of subjects and promote new drug discovery and integrate with international standards.

OBJECTIVE:To Provide reference for improving teaching levels of New Drug Clinical Research and training for pharmaceutical research talents. METHODS:The experiment teaching in 2013 graduate student of the Fourth Military Medical Uni-versity was taken as a pilot,different teaching methods were introduced in various chapters of New Drug Clinical Research,and ap-praisal system was perfected. RESULTS & CONCLUSIONS:Some appropriate methods are established,for example,conductive teaching,problem-based learning,spot-teaching and bilingual-teaching. The appraisal system including usual performance and re-search proposal is established,it has improved enthusiasm and initiative of students,promoted teaching quality,obtained certain achievements,which provides reference for the training methods on the cultivation of innovative and professional pharmaceutical tal-ents.

Aiming at building research disciplines,Xijing hospital has initially achieved a strategic transformation into a hospital with research disciplines,with such measures as scientific layout of disciplines,making of advantageous disciplines with overseas benchmarks,encouragement of potential disciplines with advantageous disciplines,promotion of medical innovation with innovative ideas,and upgrading clinical service quality with technical innovation.