新一代PEG在修饰抗原和药物缓释中的应用

聚乙二醇及其衍生物是具有许多优良性质的高分子化合物,由于良好的生物相容性、无毒、无免疫原性,广泛用于生物医学领域。本文总结聚乙二醇的发展历史和新一代聚乙二醇的特点,阐述聚乙二醇化修饰的目的,特别是在抗原修饰、血型改造和细胞移植等方面的应用,重点对聚乙二醇在药物缓释方面的应用进行了系统的综述。     

Landscape simplification increases vineyard pest outbreaks and insecticide use

Diversifying agricultural landscapes may mitigate biodiversity declines and improve pest management. Yet landscapes are rarely managed to suppress pests, in part because researchers seldom measure key variables related to pest outbreaks and insecticides that drive management decisions. We used a 13‐year government database to analyse landscape effects on European grapevine moth (Lobesia botrana) outbreaks and insecticides across c. 400 Spanish vineyards. At harvest, we found pest outbreaks increased four‐fold in simplified, vineyard‐dominated landscapes compared to complex landscapes in which vineyards are surrounded by semi‐natural habitats. Similarly, insecticide applications doubled in vineyard‐dominated landscapes but declined in vineyards surrounded by shrubland. Importantly, pest population stochasticity would have masked these large effects if numbers of study sites and years were reduced to typical levels in landscape pest‐control studies. Our results suggest increasing landscape complexity may mitigate pest populations and insecticide applications. Habitat conservation represents an economically and environmentally sound approach for achieving sustainable grape production.     

Safety zones for a Sclerotinia sclerotiorum-based mycoherbicide: Accounting for regional and yearly variation in climate

Variation in the width of 'safety zones' for sheep and dairy pasture treated with a Sclerotinia sclerotiorum (Lib.) de Bary-based mycoherbicide was quantified using 10 years of climate data from each of five regions in New Zealand. Acceptable and risk-averse zones were defined as the maximum distances in any direction from a treated pasture where 'added:natural' ratios of air-borne S. sclerotiorum spores are 1:1 and 1:10, respectively. The 10-year mean 1:1 safety zone had zero width for sheep pasture at all locations, and was at most, 50 m wide for dairy pasture. The width of the 10-year mean 1:10 zone varied regionally from 314 to 443 m for sheep and from 175 to 280 m for dairy pasture, and the 90th percentile 1:10 zones were up to 41% wider. Linear relationships between safety zone width and mean wind speed were evident and these could be used to derive region-specific safety zones.     

Rapid pre-screening of cervical smears as a method of internal quality control in a cervical screening programme

Objective:  To evaluate the performance of rapid pre-screening (RPS) as a method of internal quality control in the cytopathological examination of cervical smears for cervical cancer screening.
Methods:  The sample consisted of 6135 cervical smears submitted to RPS and routine screening (RS) methods. The smears classified as negative in RPS and RS were considered final diagnoses, and were not, therefore, submitted to any additional review. The smears identified as suspect or unsatisfactory according to RPS were analysed separately by two different cytologists irrespective of the diagnosis reached in RS. Smears considered abnormal or unsatisfactory at RS were also reviewed. When both cytologists issued concordant diagnoses, this was considered the final diagnosis. Discordant results were analysed by a third cytologist and a consensus meeting was held to define the final diagnosis.
Results:  Taking abnormalities detected by RS as the denominator, RPS had a sensitivity of 63.0% for the detection of all abnormal smears and 96.7% for high grade squamous intraepithelial lesion (HSIL). When compared with the final diagnosis, sensitivity of RPS for all abnormal smears was 74.9% and for HSIL 95.0%. Of the 529 abnormal smears confirmed in the final diagnosis, 2.15% were detected only by the RPS.
Conclusion:  RPS is an effective alternative method of internal quality control with high sensitivity for the detection of more severe lesions. It also permits monitoring of the laboratory rate of false-negative results, and allows constant evaluation of the performance both of the pre-screening and RS cytologists.     

Enhancing pest control in annual crops by conservation of predatory Heteroptera

Conservation biological control (CBC) combines a diverse set of actions aiming to enhance pest regulation by the provision of pest natural enemies’ preservation in the crop environment. This is accomplished through appropriate implementation practices and the creation of infrastructures of non-crop vegetation. On most annual crops, omnivorous heteropteran predators comprise the main assemblage of native natural enemies. Their populations, when protected from pesticides, have shown a high potential in biological control. Aiming to promote their functioning in CBC, efforts targeted to modify the crop environment are focusing on the determination of their non-crop host plants that can support the predators’ persistence as well as the emigration of these predators to the nearby crops. Nonetheless, relatively few studies seek to collect essential and adequately verified data for the practical implementation of CBC approaches. In this review, the advances already developed are illustrated, the shortcomings are discussed and the future research needs are highlighted in an effort to intensify efforts for CBC developments on annual crops.     

Conformational control in structure-based drug design

In structure-based drug design, the basic goal is to design molecules that fit complementarily to a given binding pocket. Since such computationally modeled molecules may not adopt the intended bound conformation outside the binding pocket, one challenge is to ensure that the designed ligands adopt similar low energy conformations both inside and outside of the binding pocket. Computational chemistry methods and conformational preferences of small molecules from PDB and Cambridge Structural Database (CSD) can be used to predict the bound structures of the designed molecules. Herein, we review applications of conformational control in structure-based drug design using selected examples from the recent medicinal chemistry literature. The main purpose is to highlight some intriguing conformational features that can be applied to other drug discovery programs.     

Developability studies before initiation of process development

Monoclonal antibodies constitute a robust class of therapeutic proteins. Their stability, resistance to stress conditions and high solubility have allowed the successful development and commercialization of over 40 antibody-based drugs. Although mAbs enjoy a relatively high probability of success compared with other therapeutic proteins, examples of projects that are suspended due to the instability of the molecule are not uncommon. Developability assessment studies have therefore been devised to identify early during process development problems associated with stability, solubility that is insufficient to meet expected dosing or sensitivity to stress. This set of experiments includes short-term stability studies at 2−8 þC, 25 þC and 40 þC, freeze-thaw studies, limited forced degradation studies and determination of the viscosity of high concentration samples. We present here three case studies reflecting three typical outcomes: (1) no major or unexpected degradation is found and the study results are used to inform early identification of degradation pathways and potential critical quality attributes within the Quality by Design framework defined by US Food and Drug Administration guidance documents; (2) identification of specific degradation pathway(s) that do not affect potency of the molecule, with subsequent definition of proper process control and formulation strategies; and (3) identification of degradation that affects potency, resulting in program termination and reallocation of resources.     

Ribeiroia marini: pathogenesis and larval trematode antagonism in the snail, Biomphalaria glabrata

Larval trematode antagonism between Ribeiroia marini and Schistosoma mansoni was studied in the snail Biomphalaria glabrata. A laboratory-raised Puerto Rican strain of B. glabrata was exposed to single and double infections with given numbers of: (1) embryonated eggs of R. marini from laboratory rats, and (2) miracidia of S. mansoni from mice. Snails were maintained in outside environmental tanks in San Juan, Puerto Rico and larval trematode interactions were examined in a series of five experiments. Snails of all sizes were highly susceptible to single infections with R. marini. Rediae and cercariae caused extensive damage to the digestive gland and ovotestis resulting in premature death of snails. Heavily infected snails were castrated and stopped laying eggs. Snails infected first with S. mansoni were only partly susceptible to superinfection with R. marini given on Day 23. In a reverse experiment, snails infected first with R. marini were only partly susceptible to a second infection with S. mansoni given on Day 23. In simultaneous exposures, snails developed double infections (22%) with R. marini dominant and S. mansoni sporocyst and cercaria production reduced. While R. marini is not a strong direct antagonist against established S. mansoni infections, it has several attributes as a possible biological control agent: hardy eggs easily produced in rats; high infectivity to snails of all ages; and ability to castrate and prematurely kill B. glabrata. The R. marini-rat system described here provides a convenient laboratory and field model for the study of intrasnail trematode antagonism and biological control.     

Life history and host range of the leaf blotcher Eucosmophora schinusivora: a candidate for biological control of Schinus terebinthifolius in the USA

The host range of Eucosmophora schinusivora Davis and Wheeler (Lepidoptera: Gracillariidae) was studied to assess its suitability as a biological control agent of Schinus terebinthifolius Raddi (Anacardiaceae), a serious environmental and agricultural weed in the USA and elsewhere in the world. The life history of this insect species and its host range were determined in the laboratory with adult no-choice oviposition and larval development tests. This species has five instars, the first three are sap-feeding miners and the last two are tissue feeding. Total development time was 31.7 days. To examine specificity of this species, 10 plant species in Anacardiaceae were selected based on taxonomic relatedness to S. terebinthifolius, economic importance, and availability. In the laboratory, except for Anacardium occidentale and Cotinus obovatus, all of the tested species were accepted for oviposition with a marked preference for the weed S. terebinthifolius, Schinus molle, Rhus copallinum, Rhus sandwicensis and Pistacia chinensis. Complete development, from egg to adult, was achieved only on S. terebinthifolius, S. molle, R. copallinum, P. chinensis and Metopium toxiferum. In conclusion, E. schinusivora will not be considered for the biological control of S. terebinthifolius in the continental USA. However, the utilisation of this species in other infested areas such as Hawai'i and Australia should be considered.     

A time–frequency approach to estimate critical time intervals in postural control

The critical time interval (CTI) is a parameter that has been used to distinguish open-loop from closed-loop control during upright stance. The aim of this study was to develop a new method to determine CTIs. The new approach, termed the intermittent critical time interval (ICTI) method, was motivated from evidence that upright standing is an intermittent rather than an asymptotic stability control process. For this ICTI method, center-of-pressure time series are first transformed to the time–frequency domain with a wavelet method. Subsequently, the CTI is assumed equal to the time span between two local maxima in the time–frequency domain within a distinct frequency band (i.e., 0.5–1.1 Hz). This new method may help facilitate better estimates of the transition time interval between open and closed-loop control during upright stance and can also be applied in future work such as in simulating postural control. In addition, this method can be used in future work to assess temporal changes in CTIs.