摘要：Human rhinoviruses(HRVs)are the predominant infectious agents for the common cold *** HRV-C species cause severe illnesses in children and are closely related to acute exacerbations of asthma.3C protease,a highly conserved enzyme,cleaves the viral polyprotein during replication and assists the virus in escaping the host immune *** key roles make 3C protease an important drug target.A few structures of 3Cs complexed with an irreversible inhibitor rupintrivir have been *** structures shed light on the determinants of drug *** we describe the structures of HRV-C153C in free and inhibitor-bound *** volume-decreased S1'subsite and half-closed S2 subsite,which were thought to be unique features of enterovirus A 3C proteases,appear in the HRV-C 3C *** assumes an“intermediate”conformation in the complex,which might open up additional avenues for the design of potent antiviral *** of the features of the three-dimensional structures and the amino acid sequences of 3C proteases suggest new applications for existing drugs.

摘要：Phage-inducible chromosomal islands(PICIs)are a widespread family of mobile genetic elements,which have an important role in bacterial *** elements mobilize among bacterial species at extremely high frequencies,representing an attractive tool for the delivery of synthetic ***,tools for their genetic manipulation are limited and timing ***,we have adapted a synthetic biology approach for rapidly editing of PICIs in Saccharomyces cerevisiae based on their ability to excise and integrate into the bacterial chromosome of their cognate host *** proof of concept,we engineered several PICIs from Staphylococcus aureus and Escherichia coli and validated this methodology for the study of the biology of these elements by generating multiple and simultaneous mutations in different PICI *** biotechnological purposes,we also synthetically constructed PICIs as Trojan horses to deliver different CRISPR-Cas9 systems designed to either cure plasmids or eliminate cells carrying the targeted *** results demonstrate that the strategy developed here can be employed universally to study PICIs and enable new approaches for diagnosis and treatment of bacterial diseases.

摘要：罗伯特.柯霍(RobertKoch)因对结核病(TB)的贡献荣获诺贝尔奖已过去100年,Albert Calmette和Camille Guerin制备了减毒疫苗株——牛分枝杆菌卡介苗(BCG)也已过去85年,但是,至今仍然没有有效预防TB的方法。然而,21世纪的最初十年将会见证若干新型候选疫苗的临床试验。这些候选疫苗分为二类:1)亚单位疫苗旨在强化由BCG初免诱导的免疫反应,2)改进的重组BCG取代现有的疫苗株。分别使用合适的佐剂、递送系统的蛋白质和DNA疫苗、重组病毒载体如重组的改良疫苗病毒安卡拉(Ankara),用于强化免疫,现正在试验中。已经开发出重组卡介苗(rBCG)用于初免,这些疫苗株具有很高的免疫原性,或者主要抗原的高表达。这些候选疫苗会在2006年底前通过Ⅰ期临床试验。今后的目标是试验这些新候选疫苗的不同组合以促进最佳免疫接种方案的形成。

摘要：This study was performed to demonstrate the transportation of an engineered MSC-produced intracellular anticancer gene product between mesenchymal stem cell (MSC) and cancer cells.? MSC-mediated anticancer strategy has held great promise owing to MSCs’ capacity of tumor-directed migration and the availability of specific anticancer genes.? All anticancer genes that have been used in previous MSC-mediated anticancer studies were limited in functioning via extracellular mechanisms, mainly because of the restriction by cell membrane to macromolecules including proteins.? In order to apply the majority of potent anticancer genes to the MSC-mediated anticancer system, a specifically designed expression vector which bears an intracellular anticancer gene, PTEN, is utilized to demonstrate the feasibility of the system in cancer therapies.? A transacting activator of transcription (TAT) was introduced into an expression vector followed by a segment for PTEN-RFP fusion protein.? A direct demonstration of PTEN-RFP transportation between MSC and cancer cells was obtained from direct co-cultures.? A marked cancer cell death was observed in indirect co-cultures with conditioned media from PTEN-transfected MSCs.? The demonstration of PTEN-engineered MSC-produced PTEN transportation indicates the feasibility of applying intracellular anticancer gene expression system in MSC-mediated strategies for cancer therapy.

摘要：The global increase in the prevalence of drug-resistant bacteria has necessitated the development of alternative treatments that do not rely on conventional antimicrobial *** bacteriophage-derived lytic enzymes in antibacterial therapy shows promise;however,a thorough comparison and evaluation of their bactericidal efficacy are *** study aimed to compare and investigate the bactericidal activity and spectrum of such lytic enzymes,with the goal of harnessing them for antibacterial ***,we examined the bactericidal activity of spanins,endolysins,and holins derived from 2 Escherichia coli model phages,T1 and *** these,T1-spanin exhibited the highest bactericidal activity against ***,we expressed T1-spanin within bacterial cells and assessed its bactericidal activity.T1-spanin showed potent bactericidal activity against all clinical isolates tested,including bacterial strains of 111 ***,2 Acinetobacter spp.,3 Klebsiella spp.,and 3 Pseudomonas *** contrast,T1 phage-derived endolysin showed bactericidal activity against *** and ***,yet its efficacy against other bacteria was inferior to that of ***,we developed a phage-based technology to introduce the T1-spanin gene into target *** synthesized non-proliferative phage exhibited strong antibacterial activity against the targeted *** potent bactericidal activity exhibited by spanins,combined with the novel phage synthetic technology,holds promise for the development of innovative antimicrobial agents.

摘要：Objectives: Antiretroviral therapy (ART) has been associated with lipodystrophy in children. We evaluated changes in various anthropometric measurements for the assessment of lipodystrophy and assessed whether there was an association with use of protease inhibitors (PI), non-PI containing ART and/or stavudine (d4T). Methods: Eighty-five HIV-infected children attending the HIV clinic at Great Ormond Street Hospital (GOSH) were included. The average follow-up was 8.4 months (range 3 - 12 months). Body fat redistribution was assessed by anthropometric measurements including skinfold thickness and circumferences of upper and lower limbs. Measurements were converted to age- and sex-adjusted z-scores through development stages including puberty. Results: Sixty children had taken ART;37 received PI-containing;38 received d4T;25 had never been treated. In the studied population, clinically important changes with decreases in biceps (BSF), subscapular skinfolds and total body fat (4SFT) over period of 12 months were observed. Some increase was noticed in triceps skinfolds (TSF). Limbs circumferences remained at the same level. Further we looked at 4 months basis changes in anthropometric measurements stratified by baseline ART. Generally z-scores of anthropometric measurements were lower in therapy naive children when compared to ART groups. PI-based ART regimens resulted in significant increases in BSF with a trend towards increases in TSF, suprailiac and 4SFT. Mid-arm and thigh circumferences were higher in PI compared to naive group. Similarly, significant changes in BSF z-scores were associated with d4T use. Increases were seen in TSF and mid-arm circumference and decreases were observed in subscapular skinfolds and calf circumference z-scores. Conclusions: Body fat redistribution in HIV-infected children with sub-clinical lipodystrophy could be detected by anthropometric measurements, particularly when PI or d4T is included in ART. Over time, changes with increase in a