Background and purpose:Transmembrane and coiled-coil domains 1(TMCO1)is a recently discovered endoplasmic reticulum calcium channel protein that has been found to be associated with the progression of various tumors,however,its role in cervical cancer has not yet been clarified.This study aimed to investigate the effects of TMCO1 on the proliferation and migration of cervical cancer HeLa cells.Methods:By transfecting cervical cancer HeLa cells with plasmids,cells with stable overexpression of TMCO1 and cells with stable knockdown of TMCO1 were obtained.Cell counting kit-8(CCK-8)assay,clone formation assay and EdU labeling assay were used to detect cell proliferation ability,transwell assay was used to detect cell migration ability,and proteomic analysis was performed on the cells that stably overexpressed TMCO1 and control cells.Results:TThe CCK-8 experiment and clone formation experiment showed that overexpression of TMCO1 in cervical cancer HeLa cells significantly increased their proliferation ability(P＜0.05).EdU labeling experiments showed that overexpression of TMCO1 in cervical cancer HeLa cells significantly increased the number of cells undergoing active DNA synthesis(P＜0.01).After knocking down TMCO1 in cervical cancer HeLa cells,the expression of cell cycle inhibitory protein p27 increased,and the phosphorylation of histone H3 decreased.Clonogenesis experiments showed that knocking down TMCO1 significantly inhibited the proliferation of cervical cancer HeLa cells(P＜0.001).EdU labeling experiments showed that after knocking down TMCO1 in cervical cancer HeLa cells,the number of cells undergoing active DNA synthesis was significantly reduced(P<0.05).Transwell experiment showed that overexpression of TMCO1 in cervical cancer HeLa cells significantly increased their migration ability(P＜0.001),while knocking down TMCO1 significantly inhibited the migration of cervical cancer HeLa cells(P＜0.001).The pathways related to extracellular matrix adhesion and PI3K-AKT signaling were significantly upregulated in the cells with stable overexpression of TMCO1,while ribosome related pathways were downregulated in proteomic analysis.Conclusion:Overexpression of TMCO1 significantly promotes the proliferation and migration of cervical cancer cells,while knockdown of TMCO1 significantly inhibits the proliferation and migration of cervical cancer HeLa cells.TMCO1 may affect the proliferation and migration of HeLa cells by regulating cell adhesion and signal transduction.

OBJECTIVE：To understand the current situation and existing problems of Blumea balsamifera industry in China ， and to provide reference for its sustainable development . METHODS ：With the keywords of “B. balsamifera ”“Ai Pian ”“Ai Fen ”， etc.，through the patent platform of SooPat and Baiten ，the patent data of B. balsamifera that had been published from Jan. 1989 to Dec. 2019 were collected. The International Patent Classification （IPC）was used to sort out and count the patent information of B. balsamifera，to understand the development status of B. balsamifera industry in technology and research field ，to analyze the existing problems and to explore the development trend of B. balsamifera industry in China so as to put forward corresponding suggestions. RESULTS & CONCLUSIONS：A total of 690 patents related to B. balsamifera were collected ，mainly invention patents，of which the authorization rate was 27.39％，the effective rate was 17.97％，and the failure rate was 55.22％. Top 10 applicants with the largest number of applications had a total of 165 applications，accounting for 23.91％ of the total number of applications. Top 10 applicants were 4 enterprises，3 natural persons and 3 colleges and universities. The patents of B. balsamifera were mainly distributed in Guizhou ，Shandong，Anhui，Guangdong，Guangxi and Hainan ，accounting for 81.01％ of the total patent applications of B. balsamifera . The patent technology field of B. balsamifera had expanded from traditional Chinese medicine to daily chemical products ，health care and physiotherapy and other daily consumer good fields. From the perspective of patent intensity，the number and quality of patent applications were not coordinated ，and there were many meaningless patent applications，and the conversion rate was low. It is suggested that China should strengthen the research on B. balsamifera and its more compatible medicinal materials ，promote the innovation ，development，transformation and upgrading of B. balsamifera industry；strengthen the systematic and in-depth research on B. balsamifera，improve the quality and conversion rate of patent xiexiaoli13@126.com technology，and revitalize the development of B. balsamifera industry； expand multi-party cooperation ， strengthen the E-mail：fulai.yu@163.com research on patent core technology ，build the strategic alliance of intellectual property rights of B. balsamifera industry，and realize the high quality development of B. balsamifera industry.

Endophytic fungus is an important treasure trove for discovery of structurally unusual and biologically diverse compounds. A phytochemical investigation on a fungus Clonostachys rosea inhabits inner tissue of Blumea balsamifera (L.) DC. was initiatedrecently in our lab. Six pure compounds were isolated through silica gel column chromatography, sephadex LH-20, and semi-preparative HPLC techniques, with bio-guided strategy. Their structures were characterized as verticillin A (1), (S)-(+)-fusarinolic acid (2), 8-hydroxyfusaric acid (3), cerebroside C (4), 3-Maleimide-5-oxime (5), and bionectriol A (6) by analyses of NMR and MS data. All compounds were tested in vitro antibacterial activities against four strains of bacteria, Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa, and results revealed that 1, 4 and 6 display notableinhibition againstthree bacteria, with MIC values ranging from 2 to 16 μg/mL. Our findings provide references for mining novel antibiotics from endophytes originated from Li Minority medicinal plant B. balsamifera (L.) DC.

The introduction of the mevalonate pathway (MVA pathway) in recombinant Escherichia coli can improve the synthesis of terpenoids. But the imbalance expression of MVA pathway genes and accumulation of intermediates inhibit cell growth and terpenoids production. In this study, each gene of MVA pathway and key genes of lycopene synthesis pathway were cloned in plasmid to express in the recombinant E. coli LYC103 with optimizing the expression of the key genes of the 2-methyl-D-erythritol-4-phosphate pathway (MEP pathway), chromosome recombinant MVA pathway and the lycopene synthesis pathway. The results showed that the overexpression of ispA, crtE, mvaK1, idi and mvaD genes did not affect the cell growth, while lycopene production increased by 13.5%, 16.5%, 17.95%, 33.7% and 61.1% respectively, indicating that these genes may be the rate-limiting steps for the synthesis of lycopene. mvaK1, mvaK2, mvaD of MVA pathway were the rate-limiting steps and were in an operon. The mvaK1, mvaK2, mvaD operon was regulated by mRS (mRNA stabilizing region) library in front of mvaK1, obtaining strain LYC104. Lycopene yield of LYC104 was doubled and cell growth was increased by 32% compared with the control strain LYC103. CRISPR-cas9 technology was used to integrate idi into chromosome at lacZ site to obtain LYC105 strain. Cell growth of LYC105 was increased by 147% and lycopene yield was increased by 2.28 times compared with that of LYC103. In this study, each gene of lycopene synthesis pathway was expressed in plasmid to certify the rate-limiting gene based on the complete MVA pathway on the chromosome. Then the rate-limiting gene was integrated in chromosome with homologous recombination to release the rate-limiting, which providing a new strategy for the construction of high-yield strains for metabolic engineering.

Isoprenoids are all derived from two five-carbon building blocks called isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), which are synthesized either by the mevalonate (MVA) pathway or 2-C-methyld-D-erythritol-4-phosphate (MEP) pathway. In this study, the MVA pathway genes were integrated into the chromosome of LYC101, in which the expression of key genes in the MEP synthesis pathway and lycopene synthesis pathway were optimized by artificial regulatory parts, to further improve the production of isoprenoids in Escherichia coli. The plasmids pALV23 and pALV145 were screened from a plasmid library that constructed by using the RBS library to link the genes of the MVA pathway, which greatly increased the production of β-carotene. The effects of plasmids pALV23 and pALV145 on the lycopene production in low and high lycopene production strain, LYC001 and LYC101, were compared, respectively. The production of lycopene was increased by plasmids pALV23 and pALV145 in both strains. In high lycopene production strain LYC101, pALV23 produced more lycopene than pALV145. Then, the MVA gene together of promoter of pALV23 was integrated into the chromosome of LYC101 at poxB site using method of homologous recombination helped by CRISPR-Cas9 system, resulted in genetically stable strain, LYC102. The yield of lycopene of LYC102 was 40.9 mg/g DCW, 1.19-folds higher than that of LYC101, and 20% more than that of LYC101 with pALV23. Simultaneous expression of MVA pathway and MEP pathway in recombinant E. coli can effectively increase the yield of terpenoids. In this study, a plasmid-free, genetically stable, high-yielding lycopene strain was constructed, which could be used for industrialization. Also, the platform strain can be used for the synthesis of other terpenoids.
Chromosomes, Bacterial ; Escherichia coli ; Lycopene ; Mevalonic Acid ; beta Carotene

Misuse and abuse of veterinary antimicrobial agents have led to an alarming increase in bacterial resistance, clinical treatment failure, and drug residues. To address these problems, consistent and appropriate dosage regimens for veterinary antimicrobial agents are needed. Pharmacokinetics/Pharmacodynamics (PK/PD) models have been widely used to establish rational dosage regimens for veterinary antimicrobial agents that can achieve effective prevention and treatment of bacterial diseases and avoid the development of bacterial resistance. This review introduces building methods for PK/PD models and describes current PK/PD research progress toward rational dosage regimens for veterinary antimicrobial agents. Finally, the challenges and prospects of PK/PD models in the design of dosage regimens for veterinary antimicrobial agents are reviewed. This review will help to increase awareness of PK/PD modeling among veterinarians and hopefully promote its development and future use.
Anti-Infective Agents ; Bacterial Infections ; Drug Residues ; Humans ; Treatment Failure ; Veterinarians

Objective: To investigate the reproductive health status of female workers in petrochemical industry, and to provide a reference for improving reproductive health status and developing preventive and control measures for female workers in petrochemical industry. Methods: A face-to-face questionnaire survey was performed from January to October, 2016. The Questionnaire on Women's Reproductive Health was used to investigate the reproductive health of female workers in petrochemical industry. The multivariate logistic regression model was used to identify the influencing factors for reproductive health of female workers in petrochemical industry. Results: Among the 7485 female workers, 1 268 (40.9%) had abnormal menstrual period, 1 437 (46.4%) had abnormal menstrual volume, 177 (28.5%) had hyperplasia of mammary glands, and 1 807 (24.6%) had gynecological inflammation. The reproductive system diseases in female workers in petrochemical industry were associated with the factors including age, marital status, education level, unhealthy living habits, abortion, overtime work, work shift, workload, video operation, occupational exposure, positive events, and negative events, and among these factors, negative events (odds ratio[OR]= 1.856) , unhealthy living habits (OR=1.542) , and positive events (OR=1.516) had greater impact on reproductive system diseases. Conclusion Many chemical substances in the occupational environment of petrochemical industry can cause damage to the reproductive system, which not only affects the health of the female workers, but also poses potential threats to the health of their offspring. Occupational exposure, unhealthy living habits, overtime work, and work shift have great influence on reproductive system diseases in female workers.

Blumea balsamifera resource is an important material foundation for the breeding,quality identification,genetic research,biotechnology research and agricultural production.It is also the material basis for sustainable development of Blumea balsamifera.In this paper,we reviewed the related research on Blumea balsamifera resources in China,and discussed existing problems of Blumea balsamifera resources,and put forward some suggestions on key research direction in the future,for peer reference and discussion in use and further study promotion of Blumea balsamifera resources.

HPLC-ICP-MS method was established to separate AsB, As(Ⅲ), monmethyl arsenic ( MMA ) , dimethyl arsenic ( DMA ) and As(V) in rat viscera. Ultrasonic water bath extraction was used for sample pretreatment. Dionex IonPac AS19 anion-exchange column and 20 mmol/L (NH4)2CO3(pH=9. 7) were used to analyze arsenic species in rat liver and kidney after realgar infected. The results showed that the method was not interfered by 40 Ar35 Cl+ peak, the linear ranges for five arsenic species were all between 1 and 300 μg/L with linear coefficients more than 0. 9990, and the detection limits were between 0. 3 and 0. 5 μg/L. The relative standard deviations ( RSDs) for the determination of five species were less than 5% and the recoveries were between 83. 8% and 111. 7%. After speciation analysis, DMA, As(Ⅲ) and unknown compound 2 were found in liver;DMA, MMA, As(Ⅲ), unknown compound 1, unknown compound 2 and unknown compound 3 were found in the kidney. The results indicated that this method could be used for arsenic species analysis of realgar metabolism.

Objective To investigate the causes of death between the old and the no-old inpatients with psychosis.Methods 203 patients died during 2002～2006 in our hospital were divided into the old group(≥60 years old,112 cases) and non-old group(<60 years old,91 case) according to the age of death,and analyzed.Results The old group suffered from organic psychosis mostly,and physical disease and sudden death were the main death of them.Non-old group suffered from schizophrenia and emotion disorder mostly,and physical disease,suicide and sudden death were the main death of them.Conclusion The mortality of old inpatient with psychosis is higher than that of the non-old inpatients.There were some differences between the death of them.